ɍɇɂȼȿɊɁɂɌȿɌ ɍ ɄɊȺȽɍȳȿȼɐɍ ɎȺɄɍɅɌȿɌ ɆȿȾɂɐɂɇɋɄɂɏ ɇȺɍɄȺ Ⱦɪ ɦɟɞ. Ɇɢɪʁɚɧɚ Ɇɢʁɭɲɤɨɜɢʄ ȾɂȳȺȽɇɈɋɌɂɑɄɂ ɁɇȺɑȺȳ ɉɊɈɌȿɂɇȺ ɈɒɌȿȶȿȵȺ ȻɍȻɊȿȽȺ-1 (KIM-1) ɂ ȺɄȼȺɉɈɊɂɇȺ 1 (AQP-1) ɄɈȾ ȻɈɅȿɋɇɂɄȺ ɄɈȳɂ ȻɈɅɍȳɍ ɈȾ ɄȺɊɐɂɇɈɆȺ ɋȼȿɌɅɂɏ ȶȿɅɂȳȺ ȻɍȻɊȿȽȺ ȾɈɄɌɈɊɋɄȺ ȾɂɋȿɊɌȺɐɂȳȺ Kɪɚɝɭʁɟɜɚɰ, 2015. ɝɨɞ. ෌ฃкฃ෿о෸෷р෮෴෵оฃ෰෵о෴ฃкฉฃрจк෵о෴෸จ෵рฉ෮ฏ෸ј෵о෸෿෮෾෮оจ෮෿оคฃ෿ฃћо෸оคฃ෴ршкуо෴෸෰н෸ฎоะу෴෸,окฃј෸෿෮о෶෵෾෸෿о෴෮оจ෵о෷෮ฎ෰෮෾෸෿: ෇෵෸෷෿෵рнуо ෷෮ฎ෰෮෾нฃจฉо ෴угуј෵෿о ෿ฃ෿о ෿෵нฉฃру,о ෉рฃญ.о ෴ро Д෵ј෮нуо ෉෵ฉрฃ෰෸ћу,о кฃј෸о ј෵о จ෮о ෿нฃ෿ คрฃш෮ฃо คуฉо ฃ෴о ෸෴෵ј෵о ෴ฃо р෵෮෾෸෷෮ฏ෸ј෵о෴ฃкฉฃрจкฃгор෮෴෮,о෴෮јућ෸ ෿෸о෰෵෾෸куоจฉручнуо෸оคр෸ј෮ฉ෵ะจкуоคฃ෿ฃћо෸оคฃ෴ршку ඼෵෾෸куо෷෮ฎ෰෮෾нฃจฉо෴угуј෵෿о෉рฃญ.о෴ро෇ฃ෰෮куоෆ෸෾ฃ෰෸ћу,он෮оคру෶෵нฃјош෮нจ෸о෴෮оจ෵о෯෮෰෸෿оคฃะ෵෿он෵ญрฃ-ฃнкฃ෾ฃг෸ј෵,о у෰෵ко คр෸ј෮ฉ෵ะจкฃјо෸окฃ෾෵г෸ј෮෾нฃјоคฃ෿ฃћ෸о෸оคฃ෴ршฏ෸о ෇෵෸෷෿෵рнฃоฎ෰෮෾෮о෉рฃญ.о෴ро෋н෵෶෮н෸оැ෵рฃ෰෸ћ,он෮о෰෵෾෸кฃјоจฉручнฃјо෸оคр෸ј෮ฉ෵ะจкฃјоคฃ෿ฃћ෸о෸о у෰෵кокฃр෸จн෸෿оจ෮෰෵ฉ෸෿෮о ฉฃкฃ෿о෸෷р෮෴෵о෴ฃкฉฃрจкฃгор෮෴෮ ෇෵෸෷෿෵рну ෷෮ฎ෰෮෾нฃจฉо෴угуј෵෿о෉рฃญ. ෴роД෮н෸෾уо඼ฃј෰ฃ෴෸ћу,окฃј෸о෿෸ој෵оคру෶෸ฃоฃгрฃ෿нуоจฉручнуо෸оคр෸ј෮ฉ෵ะจкуоคฃ෿ฃћо෸о คฃ෴ршкуо෸оч෸ј෸оจ෮෰෵ฉ෸оจуо෿෸о෯෸෾෸оฃ෴он෵คрฃฏ෵ั෸෰෵о෰р෵෴нฃจฉ෸ ฉฃкฃ෿о෸෷р෮෴෵о෴ฃкฉฃрจкฃгор෮෴෮ ෂจкр෵нуо ෷෮ฎ෰෮෾нฃจฉо ෴угуј෵෿оෆро จฏ ෿෵෴. ෂ෰෮нуо෋ฉ෮нฃј෵෰෸ћуо෸о ฃจฃ෯ะуоළ෮෯ฃр෮ฉฃр෸ј෵о ෷෮о к෾෸н෸чкуо෸о ෵кจค෵р෸෿෵нฉ෮෾нуо ෸෿унฃ෾ฃг෸ју ඼ෆය, ශฃр෮нуо ්෮෴у෾ฃ෰෸ћу,о ඼෵р෸ฏ෸о ෋෿෸ะ෮н෸ћо ෸о ෂр෵н෸о ෆ෮рฉ෸нฃ෰෸ћ, ෯෵෷о ч෸ј෵о คฃ෿ฃћ෸о ෸о คฃ෴ршк෵о ฃ෰෮јо ෴ฃкฉฃрจк෸ор෮෴он෵о෯෸о෯෸ฃо෿ฃгућ ෂจкр෵нуо෷෮ฎ෰෮෾нฃจฉо෴угуј෵෿оෆроคฎо෌෮෿෮р෸оයнђ෵෾෸ћ,он෮оจฉручнฃјо෸оคр෸ј෮ฉ෵ะจкฃјоคฃ෿ฃћ෸о෸оคฃ෴ршฏ෸ ා෰෮෾෮оДроරฃ෶෸෴෮руоහฃ෰෮ч෵෰෸ћуон෮окฃ෾෵г෸ј෮෾нฃјо෸оจр෴෮чнฃјоคฃ෿ฃћ෸оฉฃкฃ෿о෸෷р෮෴෵о෴ฃкฉฃрจкฃгор෮෴෮ ෂจкр෵ну ෷෮ฎ෰෮෾нฃจฉо ෴угуј෵෿о ෉рฃญ.о ෴ро Др෮г෮нуо Јฃ෰෮нฃ෰෸ћуо ෸о кฃ෾෵кฉ෸෰уо හ෾෸н෸к෵о ෷෮о н෵ญрฃ෾ฃг෸јуо н෮о จฉручнฃјо ෸о คр෸ј෮ฉ෵ะจкฃјоคฃ෴ршฏ෸оо ඼෵෾෸куо෷෮ฎ෰෮෾нฃจฉо෴угуј෵෿оฃจฃ෯ะуоහ෾෸н෸к෵о෷෮оурฃ෾ฃг෸јуон෮оคฃ෿ฃћ෸о෸оคฃ෴ршฏ෸оฉฃкฃ෿о෸෷р෮෴෵о෴ฃкฉฃрจкฃгор෮෴෮ ෂจкр෵нуо ෷෮ฎ෰෮෾нฃจฉо ෴угуј෵෿о ෋෸෿ฃн෸о ෈гั෮нฃ෰෸ћо ෸о гฃจคฃ෴෸нуо ෋෮ш෸о ෆ෸෾ฃจ෮෰ะ෵෰෸ћу,о ෯෵෷о ч෸ј෵о คр෸ј෮ฉ෵ะจк෵о คฃ෿ฃћ෸о ෸෷р෮෴෮о෴ฃкฉฃрจкฃгор෮෴෮он෵о෯෸о෯෸෾෮о෿ฃгућ෮ ඼෵෾෸куо෷෮ฎ෰෮෾нฃจฉо෴угуј෵෿о෉рฃญ.о෴ро෋н෵෶෮н෸оව෸෰෮нч෵෰෸ћо෋෸෿ฃнฃ෰෸ћ,он෮оจฉручнฃјо෸окฃ෾෵г෸ј෮෾нฃјоคฃ෿ฃћ෸ ෇෵෸෷෿෵рнฃоฎ෰෮෾෮о෿ฃј෸෿орฃ෴෸ฉ෵ะ෸෿෮,окฃј෸оจуо෿෸оคру෶෸෾෸о෰෵෾෸куоะу෯෮෰о෸оу෰෵ко෯෸෾෸оу෷о෿෵н෵,о ෈грฃ෿нуо ෷෮ฎ෰෮෾нฃจฉо ෴угуј෵෿о ෿ฃјฃјо คฃрฃ෴෸ฏ෸,о ч෸ј෵о จуо ෿෸о ෰෵෾෸к෮о ะу෯෮෰,о คฃ෴ршк෮о ෸о р෮෷у෿෵෰෮ั෵о ෯෸෾෸о คฃ෴จฉр෵ко ෸о ෸нจค෸р෮ฏ෸ј෮оฉฃкฃ෿о෸෷р෮෴෵о෴ฃкฉฃрจкฃгор෮෴෮ จ෰ฃјฃј ћ෵рк෸ යн෸ ɋȺȾɊɀȺȳ 1. ɍȼɈȾ ........................................................................................................................................................................ 1 1.1. ɂɫɬɨɪɢʁɚɬ .......................................................................................................................................................... 1 1.2. ȿɩɢɞɟɦɢɨɥɨɝɢʁɚ ................................................................................................................................................ 2 1.3. ɉɚɬɨɮɢɡɢɨɥɨɝɢʁɚ ɢ ɦɨɥɟɤɭɥɚɪɧɚ ɛɢɨɥɨɝɢʁɚ ɤɚɪɰɢɧɨɦɚ ɫɜɟɬɥɢɯ ʄɟɥɢʁɚ ɛɭɛɪɟɝɚ ....................................... 3 1.4. ɉɨɞɟɥɚ ɤɚɪɰɢɧɨɦɚ ɛɭɛɪɟɝɚ ............................................................................................................................. 3 1.4.1.Ʉɚɪɰɢɧɨɦ ɫɜɟɬɥɢɯ ʄɟɥɢʁɚ ɛɭɛɪɟɝɚ ........................................................................................................... 5 1.4.2.ɉɚɩɢɥɚɪɧɢ ɤɚɪɰɢɧɨɦ ɛɭɛɪɟɝɚ .................................................................................................................. 6 1.4.3. ɏɪɨɦɨɮɨɛɧɢ ɤɚɪɰɢɧɨɦ ɛɭɛɪɟɝɚ .............................................................................................................. 7 1.4.4. Ɇɭɥɬɢɥɨɤɭɥɚɪɧɢ ɰɢɫɬɢɱɧɢ ɤɚɪɰɢɧɨɦ ɛɭɛɪɟɝɚ...................................................................................... 7 1.4.5. Ɍɪɚɧɫɥɨɤɚɰɢɨɧɢ ɤɚɪɰɢɧɨɦɢ ɛɭɛɪɟɝɚ...................................................................................................... 7 1.4.6. Ɇɭɰɢɧɨɡɧɢ ɬɭɛɭɥɚɪɧɢ ɢ ɜɪɟɬɟɧɚɫɬɢ ɤɚɪɰɢɧɨɦ ɛɭɛɪɟɝɚ ....................................................................... 8 1.4.7. Ʉɚɪɰɢɧɨɦ Ȼɟɥɢɧɢʁɟɜɢɯ ɫɚɛɢɪɧɢɯ ɤɚɧɚɥɢʄɚ ........................................................................................... 8 1.4.8.Ɇɟɞɭɥɚɪɧɢ ɤɚɪɰɢɧɨɦ ɛɭɛɪɟɝɚ .................................................................................................................. 8 1.4.9.Ʉɚɪɰɢɧɨɦ ɛɭɛɪɟɝɚ ɭɞɪɭɠɟɧ ɫɚ ɫɬɟɱɟɧɨɦ ɰɢɫɬɢɱɧɨɦ ɛɨɥɟɫɬɢ ɛɭɛɪɟɝɚ ................................................ 8 1.4.10. ɋɜɟɬɥɨʄɟɥɢʁɫɤɢ ɩɚɩɢɥɚɪɧɢ ɤɚɪɰɢɧɨɦ ɛɭɛɪɟɝɚ ................................................................................... 9 1.4.11. Ɍɭɛɭɥɨɰɢɫɬɢɱɧɢ ɤɚɪɰɢɧɨɦ ɛɭɛɪɟɝɚ ..................................................................................................... 9 1.4.12. Ʉɚɪɰɢɧɨɦ ɛɭɛɪɟɝɚ ɭɞɪɭɠɟɧ ɫɚ ɧɟɭɪɨɛɥɚɫɬɨɦɨɦ ................................................................................ 9 1.4.13. ɇɟɤɥɚɫɢɮɢɤɨɜɚɧɢ ɤɚɪɰɢɧɨɦ ɛɭɛɪɟɝɚ ................................................................................................... 9 1.5.ɄɅɂɇɂɑɄȺ ɋɅɂɄȺ ..................................................................................................................................... 10 1.5.1. ȿɧɞɨɤɪɢɧɟ ɦɚɧɢɮɟɫɬɚɰɢʁɟ ɩɚɪɚɧɟɨɩɥɚɫɬɢɱɧɨɝ ɫɢɧɞɪɨɦɚ .................................................................. 10 1.5.2. ɇɟɟɧɞɨɤɪɢɧɟ ɦɚɧɢɮɟɫɬɚɰɢʁɟ ɩɚɪɚɧɟɨɩɥɚɫɬɢɱɧɨɝ ɫɢɧɞɪɨɦɚ .............................................................. 12 1.6.ȾɂȳȺȽɇɈɁȺ ................................................................................................................................................... 14 1.7.Ɇɨɥɟɤɭɥɚɪɧɢ ɦɚɪɤɟɪɢ ɡɧɚɱɚʁɧɢ ɡɚ ɞɢʁɚɝɧɨɡɭ ɤɚɪɰɢɧɨɦɚ ɫɜɟɬɥɢɯ ʄɟɥɢʁɚ ɛɭɛɪɟɝɚ.................................... 15 1.7.1.ɉɪɨɬɟɢɧ-1 ɨɲɬɟʄɟʃɚ ɛɭɛɪɟɝɚ ................................................................................................................. 15 1.7.2. Ⱥɤɜɚɩɨɪɢɧ 1 (AQP-1) ............................................................................................................................. 20 1.8. Ʌȿɑȿȵȿ ......................................................................................................................................................... 21 1.8.1. Ɍɟɪɚɩɢʁɫɤɢ ɩɪɢɫɬɭɩɢ ɭ ɥɟɱɟʃɭ ɥɨɤɚɥɢɡɨɜɚɧɟ ɛɨɥɟɫɬɢ ....................................................................... 21 1.8.2. Ɍɟɪɚɩɢʁɫɤɢ ɩɪɢɫɬɭɩɢ ɭ ɥɟɱɟʃɭ ɦɟɬɚɫɬɚɬɫɤɟ ɛɨɥɟɫɬɢ .......................................................................... 22 1.9. ɉɪɨɝɧɨɫɬɢɱɤɢ ɮɚɤɬɨɪɢ .................................................................................................................................. 23 1.9.1. Ⱥɧɚɬɨɦɫɤɢ ɩɪɨɝɧɨɫɬɢɱɤɢ ɮɚɤɬɨɪɢ ....................................................................................................... 23 1.9.2. ɏɢɫɬɨɥɨɲɤɢ ɩɪɨɝɧɨɫɬɢɱɤɢ ɮɚɤɬɨɪɢ .................................................................................................... 24 1.9.3. Ʉɥɢɧɢɱɤɢɩɪɨɝɧɨɫɬɢɱɤɢ ɮɚɤɬɨɪɢ .......................................................................................................... 25 1.9.4. Ɇɨɥɟɤɭɥɚɪɧɢ ɩɪɨɝɧɨɫɬɢɱɤɢɦɚɪɤɟɪɢ .................................................................................................... 26 2. ɏɂɉɈɌȿɁȿ ɂ ɐɂȴȿȼɂ ɂɋɌɊȺɀɂȼȺȵȺ ................................................................................................. 27 3. ɆȺɌȿɊɂȳȺɅ ɂ ɆȿɌɈȾȿ ................................................................................................................................. 29 3.1. ɉɨɞɚɰɢ ɨ ɢɫɩɢɬɚɧɢɰɢɦɚ ɢ ɚɧɚɥɢɡɢɪɚɧɢɦ ɭɡɨɪɰɢɦɚ ................................................................................... 29 3.1.1. Ʉɥɢɧɢɱɤɟ ɤɚɪɚɤɬɟɪɢɫɬɢɤɟ ɝɪɭɩɟ ɨɛɨɥɟɥɢɯ .......................................................................................... 29 3.1.2. Ʉɥɢɧɢɱɤɟ ɤɚɪɚɤɬɟɪɢɫɬɢɤɟ ɤɨɧɬɪɨɥɧɟ ɝɪɭɩɟ ........................................................................................ 30 3.1.3.Ɉɞɪɟђɢɜɚʃɟ ɤɨɧɰɟɧɬɪɚɰɢʁɟ KIM-1 ɭ ɭɪɢɧɭ .......................................................................................... 30 3.1.4. Ɉɞɪɟђɢɜɚʃɟ ɤɨɧɰɟɧɬɪɚɰɢʁɟ AQP-1 ɭ ɭɪɢɧɭ ......................................................................................... 31 3.1.5. Ɉɞɪɟђɢɜɚʃɟ ɤɪɜɧɟ ɫɥɢɤɟ ɢ ɛɢɨɯɟɦɢʁɫɤɢɯ ɩɚɪɚɦɟɬɚɪɚ ɤɪɜɢ ............................................................... 31 3.1.6. Ɇɚɤɪɨɫɤɨɩɫɤɚ ɢ ɦɢɤɪɨɫɤɨɩɫɤɚ ɨɛɪɚɞɚ ɬɤɢɜɚ ɛɭɛɪɟɝɚ ɫɚ ɬɭɦɨɪɨɦ .................................................... 33 3.1.7.ɂɦɭɧɨɯɢɫɬɨɯɟɦɢʁɫɤɨ ɨɞɪɟђɢɜɚʃɟ ɟɤɫɩɪɟɫɢʁɟ TIM-1/KIM-1/HAVCRɭ ɬɤɢɜɧɢɦ ɩɪɟɫɟɰɢɦɚ ............. 36 3.2. ɋɬɚɬɢɫɬɢɱɤɚ ɨɛɪɚɞɚ ɩɨɞɚɬɚɤɚ ....................................................................................................................... 37 4. ɊȿɁɍɅɌȺɌɂ ......................................................................................................................................................... 38 4.1. Ɉɩɲɬɟ ɤɚɪɚɤɬɟɪɢɫɬɢɤɟ ɢɫɩɢɬɢɜɚɧɢɯ ɝɪɭɩɚ ................................................................................................. 38 4.2. Ʉɚɪɚɤɬɟɪɢɫɬɢɤɟ ɢɫɩɢɬɢɜɚɧɟ ɝɪɭɩɟ ɨɛɨɥɟɥɢɯ ɨɞ ɫɜɟɬɥɨʄɟɥɢʁɫɤɨɝ ɤɚɪɰɢɧɨɦɚ ɛɭɛɪɟɝɚ ............................ 38 4.2.1. Ʉɥɢɧɢɱɤɟ ɤɚɪɚɤɬɟɪɢɫɬɢɤɟ ɝɪɭɩɟ ɨɛɨɥɟɥɢɯ .......................................................................................... 38 4.2.2. Ȼɢɨɯɭɦɚɪɚɥɧɢ ɩɚɪɚɦɟɬɪɢ ɤɪɜɢ ɢ ɭɪɢɧɚ ɭ ɝɪɭɩɢ ɨɛɨɥɟɥɢɯ-ɩɪɟ ɢ ɩɨɫɥɟ ɨɩɟɪɚɰɢʁɟ .......................... 40 4.2.3. ɉɚɬɨɯɢɫɬɨɥɨɲɤɟ ɤɚɪɚɤɬɟɪɢɫɬɢɤɟ ɬɭɦɨɪɚ ɭ ɝɪɭɩɢ ɨɛɨɥɟɥɢɯ .............................................................. 47 4.3. Ʉɨɦɩɚɪɚɰɢʁɚ ɤɨɧɰɟɧɬɪɚɰɢʁɚ KIM-1 ɢ AQP-1 ɢɡɦɟђɭ ɢɫɩɢɬɢɜɚɧɢɯ ɝɪɭɩɚ ................................................. 53 4.3.1. Ʉɨɦɩɚɪɚɰɢʁɚ ɭɪɢɧɚɪɧɟ ɤɨɧɰɟɧɬɪɚɰɢʁɟ KIM-1 ɢɡɦɟђɭ ɢɫɩɢɬɢɜɚɧɢɯ ɝɪɭɩɚ ....................................... 53 4.3.2. Ʉɨɦɩɚɪɚɰɢʁɚ ɭɪɢɧɚɪɧɟ ɤɨɧɰɟɧɬɪɚɰɢʁɟ AQP-1 ɢɡɦɟђɭ ɢɫɩɢɬɢɜɚɧɢɯ ɝɪɭɩɚ ....................................... 57 4.4. Ʉɨɦɩɚɪɚɰɢʁɚ ɩɪɟɨɩɟɪɚɬɢɜɧɢɯɜɪɟɞɧɨɫɬɢuKIM-1ɢuAQP-1 ɢ ɩɚɬɨɯɢɫɬɨɥɨɲɤɢɯ ɤɚɪɚɤɬɟɪɢɫɬɢɤɚ ɬɭɦɨɪɚ ɭ ɝɪɭɩɢ ɨɛɨɥɟɥɢɯ...................................................................................................................................................... 59 4.4.1. Ʉɨɦɩɚɪɚɰɢʁɚ ɩɪɟɨɩɟɪɚɬɢɜɧɢɯ ɜɪɟɞɧɨɫɬɢ uKIM-1 ɢ ɩɚɬɨɯɢɫɬɨɥɨɲɤɢɯ ɤɚɪɚɤɬɟɪɢɫɬɢɤɚ ɬɭɦɨɪɚ ..... 59 4.4.2. ɂɫɩɢɬɢɜɚʃɟ ɩɨɜɟɡɚɧɨɫɬɢ ɩɪɟɨɩɟɪɚɬɢɜɧɢɯ ɜɪɟɞɧɨɫɬɢ uAQP-1 ɢ ɩɚɬɨɯɢɫɬɨɥɨɲɤɢɯ ɤɚɪɚɤɬɟɪɢɫɬɢɤɚ ɬɭɦɨɪɚ ............................................................................................................................................................... 70 4.5. ɂɫɩɢɬɢɜɚʃɟ ɩɨɜɟɡɚɧɨɫɬɢ uKIM-1 ɢ uAQP-1 ɢɜɪɫɬɟ ɨɩɟɪɚɬɢɜɧɨɝ ɥɟɱɟʃɚ ɭ ɝɪɭɩɢ ɨɛɨɥɟɥɢɯ .................. 80 4.5.1. ɂɫɩɢɬɢɜɚʃɟ ɩɨɜɟɡɚɧɨɫɬɢ uKIM-1 ɢ ɜɪɫɬɟ ɨɩɟɪɚɬɢɜɧɨɝ ɥɟɱɟʃɚ ......................................................... 80 4.5.2. ɂɫɩɢɬɢɜɚʃɟ ɩɨɜɟɡɚɧɨɫɬɢ uAQP-1 ɢ ɜɪɫɬɟ ɨɩɟɪɚɬɢɜɧɨɝ ɥɟɱɟʃɚ ........................................................ 83 4.6. ɂɫɩɢɬɢɜɚʃɟ ɩɨɜɟɡɚɧɨɫɬɢ ɬɭɦɨɪɫɤɟ ɟɤɫɩɪɟɫɢʁɟ KIM-1 ɫɚ ɤɨɧɰɟɧɬɪɚɰɢʁɨɦ uKIM-1 ɢ ɩɚɬɨɯɢɫɬɨɥɨɲɤɢɦ ɤɚɪɚɤɬɟɪɢɫɬɢɤɚɦɚ ɬɭɦɨɪɚ ɭ ɝɪɭɩɢ ɨɛɨɥɟɥɢɯ ...................................................................................................... 85 4.6.1. ɂɫɩɢɬɢɜɚʃɟ ɩɨɜɟɡɚɧɨɫɬɢ ɟɤɫɩɪɟɫɢʁɟ KIM-1 ɭ ɬɭɦɨɪɫɤɨɦ ɬɤɢɜɭ ɫɚ ɤɨɧɰɟɧɬɪɚɰɢʁɨɦ uKIM-1 ɩɪɟ ɨɩɟɪɚɰɢʁɟ ........................................................................................................................................................... 85 4.6.2. ɂɫɩɢɬɢɜɚʃɟ ɩɨɜɟɡɚɧɨɫɬɢ ɬɭɦɨɪɫɤɟ ɟɤɫɩɪɟɫɢʁɟ KIM-1 ɫɚ ɩɚɬɨɯɢɫɬɨɥɨɲɤɢɦ ɤɚɪɚɤɬɟɪɢɫɬɢɤɚɦɚ ɬɭɦɨɪɚ ............................................................................................................................................................... 86 4.7. ɂɫɩɢɬɢɜɚʃɟ ɞɢʁɚɝɧɨɫɬɢɱɤɨɝ ɩɨɬɟɧɰɢʁɚɥɚ ɩɪɟɨɩɟɪɚɬɢɜɧɢɯ ɜɪɟɞɧɨɫɬɢ uKIM-1 ɢ uAQP-1ɡɚ ɤɚɪɰɢɧɨɦ ɫɜɟɬɥɢɯ ʄɟɥɢʁɚ ɛɭɛɪɟɝɚ ......................................................................................................................................... 90 4.7.1. ɂɫɩɢɬɢɜɚʃɟ ɞɢʁɚɝɧɨɫɬɢɱɤɨɝ ɩɨɬɟɧɰɢʁɚɥɚ ɩɪɟɨɩɟɪɚɬɢɜɧɢɯ ɜɪɟɞɧɨɫɬɢ uKIM-1 ɡɚ ɤɚɪɰɢɧɨɦ ɫɜɟɬɥɢɯ ʄɟɥɢʁɚ ɛɭɛɪɟɝɚ ................................................................................................................................................... 90 4.7.2. ɂɫɩɢɬɢɜɚʃɟ ɞɢʁɚɝɧɨɫɬɢɱɤɨɝ ɩɨɬɟɧɰɢʁɚɥɚ ɩɪɟɨɩɟɪɚɬɢɜɧɢɯ ɜɪɟɞɧɨɫɬɢ ɭɪɢɧɚɪɧɟ ɤɨɧɰɟɧɬɪɚɰɢʁɟ AQP-1 ɡɚ ɤɚɪɰɢɧɨɦ ɫɜɟɬɥɢɯ ʄɟɥɢʁɚ ɛɭɛɪɟɝɚ .................................................................................................. 92 4.7.3. Ʉɨɦɩɚɪɚɰɢʁɚ ɞɢʁɚɝɧɨɫɬɢɱɤɢɯ ɩɨɬɟɧɰɢʁɚɥɚ ɢɧɢɰɢʁɚɥɧɢɯ ɜɪɟɞɧɨɫɬɢ uKIM-1 ɢ uAQP-1 ɡɚ ɤɚɪɰɢɧɨɦ ɫɜɟɬɥɢɯ ʄɟɥɢʁɚ ɛɭɛɪɟɝɚ .................................................................................................................................... 95 5. ȾɂɋɄɍɋɂȳȺ ........................................................................................................................................................ 97 5.1. Ʉɥɢɧɢɱɤɟ ɤɚɪɚɤɬɟɪɢɫɬɢɤɟ, ɮɚɤɬɨɪɢ ɪɢɡɢɤɚ ɢ ɫɢɦɩɬɨɦɢ ɩɚɪɚɧɟɨɩɥɚɫɬɢɱɧɨɝ ɫɢɧɞɪɨɦɚ ɢɫɩɢɬɢɜɚɧɟ ɝɪɭɩɟ ɨɛɨɥɟɥɢɯ ɨɞ ɤɚɪɰɢɧɨɦɚ ɫɜɟɬɥɢɯ ʄɟɥɢʁɚ ɛɭɛɪɟɝɚ ...................................................................................... 97 5.2. ȼɪɫɬɚ ɨɩɟɪɚɬɢɜɧɨɝ ɥɟɱɟʃɚ ɢ ɩɚɬɨɯɢɫɬɨɥɨɲɤɟ ɤɚɪɚɤɬɟɪɢɫɬɢɤɟ ɬɭɦɨɪɚ ɭ ɝɪɭɩɢ ɨɛɨɥɟɥɢɯ ɨɞ ɤɚɪɰɢɧɨɦɚ ɫɜɟɬɥɢɯ ʄɟɥɢʁɚ ɛɭɛɪɟɝɚ ....................................................................................................................................... 101 5.3. Ʉɨɧɰɟɧɬɪɚɰɢʁɚ KIM-1 ɭ ɭɪɢɧɭ ɨɛɨɥɟɥɢɯ ɨɞ ɤɚɪɰɢɧɨɦɚ ɫɜɟɬɥɢɯ ʄɟɥɢʁɚ ɛɭɛɪɟɝɚ................................... 105 5.4. ɉɪɟɨɩɟɪɚɬɢɜɧɟ ɜɪɟɞɧɨɫɬɢ ɤɨɧɰɟɧɬɪɚɰɢʁɟ KIM-1 ɭ ɭɪɢɧɭ ɢ ɩɚɬɨɯɢɫɬɨɥɨɲɤɟ ɤɚɪɚɤɬɟɪɢɫɬɢɤɟ ɬɭɦɨɪɚ ɭ ɝɪɭɩɢ ɨɛɨɥɟɥɢɯ ɨɞ ɤɚɪɰɢɧɨɦɚ ɫɜɟɬɥɢɯ ʄɟɥɢʁɚ ɛɭɛɪɟɝɚ ................................................................................... 107 5.5. Ʉɨɧɰɟɧɬɪɚɰɢʁɚ KIM-1 ɭ ɭɪɢɧɭ ɩɚɰɢʁɟɧɚɬɚ ɥɟɱɟɧɢɯ ɪɚɞɢɤɚɥɧɨɦ ɢ ɩɚɪɰɢʁɚɥɧɨɦ ɧɟɮɪɟɤɬɨɦɢʁɨɦ ........ 110 5.6.Ɍɤɢɜɧɚ ɟɤɫɩɪɟɫɢʁɚ KIM-1 ɤɨɞ ɤɚɪɰɢɧɨɦɚ ɫɜɟɬɥɢɯ ʄɟɥɢʁɚ ɛɭɛɪɟɝɚ ɭ ɝɪɭɩɢ ɨɛɨɥɟɥɢɯ ............................ 111 5.7. ɉɪɟɨɩɟɪɚɬɢɜɧɟ ɜɪɟɞɧɨɫɬɢ AQP-1ɭ ɭɪɢɧɭ ɢ ɩɚɬɨɯɢɫɬɨɥɨɲɤɟ ɤɚɪɚɤɬɟɪɢɫɬɢɤɟ ɬɭɦɨɪɚ ɝɪɭɩɢ ɨɛɨɥɟɥɢɯ ɨɞ ɤɚɪɰɢɧɨɦɚ ɫɜɟɬɥɢɯ ʄɟɥɢʁɚ ɛɭɛɪɟɝɚ ............................................................................................................... 114 5.8. Ⱦɢʁɚɝɧɨɫɬɢɱɤɢ ɩɨɬɟɧɰɢʁɚɥ ɩɪɟɨɩɟɪɚɬɢɜɧɢɯ ɜɪɟɞɧɨɫɬɢ ɭɪɢɧɚɪɧɢɯ ɤɨɧɰɟɧɬɪɚɰɢʁɚ KIM-1 ɢ AQP-1 ɡɚ ɤɚɪɰɢɧɨɦ ɫɜɟɬɥɢɯ ʄɟɥɢʁɚ ɛɭɛɪɟɝɚ ...................................................................................................................... 116 6. ɁȺɄȴɍɑɐɂ ....................................................................................................................................................... 118 7. ɅɂɌȿɊȺɌɍɊȺ.................................................................................................................................................... 119 ɍȼɈȾ 1 1. ɍȼɈȾ 1.1. ɂɫɬɨɪɢʁɚɬ ɉɪɜɢ ɪɚɞ ɨ „ɬɭɦɨɪɭ ɤɨʁɢ ɧɚɫɬɚʁɟ ɭ ɛɭɛɪɟɝɭ“ ɨɛʁɚɜɢɨ ʁɟ Daniel Sennert 1613. ɭ ɱɚɫɨɩɢɫɭ Practicae Medicinae. Ɂɧɚɱɚʁɧɨ ɤɚɫɧɢʁɟ, Miril ʁɟ 1810. ɨɩɢɫɚɨ ɩɪɜɢ ɧɟɞɜɨɫɦɢɫɥɟɧ ɫɥɭɱɚʁ ɤɚɪɰɢɧɨɦɚ ɛɭɛɪɟɝɚ (ɄȻ) ɤɨɞ ɬɪɭɞɧɢɰɟ ɫɬɚɪɨɫɬɢ 35 ɝɨɞɢɧɚ. ɉɪɜɭ ɯɢɫɬɨɥɨɲɤɭ ɤɥɚɫɢɮɢɤɚɰɢʁɭ ɬɭɦɨɪɚ ɛɭɛɪɟɝɚ ɧɚ ɨɫɧɨɜɭ ɦɚɤɪɨɫɤɨɩɫɤɨɝ ɢɡɝɥɟɞɚ ɨɛʁɚɜɢɨ ʁɟ Koenig 18261. Ɋɚɫɩɪɚɜɟ ɨ ɩɚɬɨɝɟɧɟɡɚ ɟɩɢɬɟɥɧɢɯ ɬɭɦɨɪɚ ɛɭɛɪɟɝɚ ɭɫɥɨɜɢɥɟ ʁɟ ɫɭ ʁɟɞɚɧ ɨɞ ɧɚʁɞɭɠɢɯ ɩɟɪɢɨɞɚ ɤɨɧɬɪɨɜɟɪɡɢ ɭ ɦɨɞɟɪɧɨʁ ɯɢɪɭɪɲɤɨʁ ɩɚɬɨɥɨɝɢʁɢ, ɤɨʁɭ ʁɟ ɢɧɢɰɢɪɚɨ Paul Grawitz ɤɨʁɢ ʁɟ 1883. ɨɛʁɚɜɢɨ ɫɜɨʁɚ ɡɚɩɚɠɚʃɚ ɨ ɦɨɪɮɨɥɨɝɢʁɢ „ɦɚɥɢɯ, ɠɭɬɢɯ ɬɭɦɨɪɚ ɛɭɛɪɟɝɚ“, ɡɚ ɤɨʁɟ ʁɟ Paul Sudeck 1893. ɭɫɬɚɧɨɜɢɨ ɞɚ ɫɭ ɦɚɥɢɝɧɢ2. Otto Lubarch УО 1894. ɭɩɨɬɪɟɛɢɨ ɬɟɪɦɢɧ „ɯɢɩɟɪɧɟɮɪɨɢɞɧɢ ɬɭɦɨɪ“ ɤɨʁɢ ʁɟ ɢɡɦɟʃɟɧ ɭ ɬɟɪɦɢɧ „ɯɢɩɟɪɧɟɮɪɨɦ“ ɨɞ ɫɬɪɚɧɟ Felix Victor Birch-Hirschfeld-ɚ, ɤɨʁɢ ʁɟ ɩɪɜɢ ɨɩɢɫɚɨ ɨɜɟ ɬɭɦɨɪɟ. Ɉɜɢ ɬɭɦɨɪɢ ɫɭ ɧɚɡɢɜɚɧɢ „ɯɢɩɟɪɧɟɮɪɨɦɢ“ ɡɛɨɝ ɯɢɫɬɨɥɨɲɤɟ ɫɥɢɱɧɨɫɬɢ ɫɚ ʄɟɥɢʁɚɦɚ ɧɚɞɛɭɛɪɟɠɧɟ ɠɥɟɡɞɟ. Foot ɢ Humphreys ɫɭ ɩɪɜɢ ɭɩɨɬɪɟɛɢɥɢ ɬɟɪɦɢɧ renal celled carcinoma, ɤɨʁɢ ʁɟ Fetter ɢɡɦɟɧɢɨ ɭ renal cell carcinoma-ɤɚɪɰɢɧɨɦ ʄɟɥɢʁɚ ɛɭɛɪɟɝɚ. Oberling ɫɚ ɫɚɪɚɞɧɢɰɢɦɚ ʁɟ 1959. ɨɩɢɫɚɨ ɭɥɬɪɚɫɬɪɭɤɬɭɪɭ ɫɜɟɬɥɢɯ ʄɟɥɢʁɚ ɤɚɪɰɢɧɨɦɚ ɛɭɛɪɟɝɚ ɢɥɢ ɫɜɟɬɥɨʄɟɥɢʁɫɤɨɝ ɤɚɪɰɢɧɨɦɚ ɛɭɛɪɟɝɚ (ɫɄȻ), ɱɢʁɚ ɰɢɬɨɩɥɚɡɦɚ ɫɚɞɪɠɢ ɛɪɨʁɧɟ ɦɢɬɨɯɨɧɞɪɢʁɟ ɢ ɞɟɩɨɡɢɬɟ ɝɥɢɤɨɝɟɧɚ ɢ ɦɚɫɬɢ, ɱɢɦɟ ʁɟ ɧɟɞɜɨɫɦɢɫɥɟɧɨ ɩɨɬɜɪђɟɧɨ ɞɚ ɨɜɟ ʄɟɥɢʁɟ ɜɨɞɟ ɩɨɪɟɤɥɨ ɨɞ ɟɩɢɬɟɥɧɢɯ ʄɟɥɢʁɚ ɩɪɨɤɫɢɦɚɥɧɨɝ ɫɚɜɢʁɟɧɨɝ ɬɭɛɭɥɚ3. Ɉɫɚɦɞɟɫɟɬɢɯ ɝɨɞɢɧɚ ɩɪɨɥɨɲɥɨɝ ɜɟɤɚ ɨɬɤɪɢɜɟɧɢ ɫɭ ɧɨɜɢ ɩɨɞɬɢɩɨɜɢ ɄȻ, ɤɚɨ ɲɬɨ ɫɭ ɩɚɩɢɥɚɪɧɢ ɢ ɯɪɨɦɨɮɨɛɧɢ, ɱɢɦɟ ʁɟ ɫɬɜɨɪɟɧɚ ɨɫɧɨɜɚ ɡɚ ɩɪɜɭ, Mainz-ɨɜɭ ɤɥɚɫɢɮɢɤɚɰɢʁɭ ɨɜɢɯ ɬɭɦɨɪɚ ɭɫɬɚɧɨɜʂɟɧɭ 1986. ɝɨɞɢɧɟ. Ɉɜɢɦ ɤɥɚɫɢɮɢɤɚɰɢɨɧɢɦ ɫɢɫɬɟɦɨɦ ɪɟɧɚɥɧɢ ɟɩɢɬɟɥɧɢ ɬɭɦɨɪɢ ɫɭ ɛɢɥɢ ɩɨɞɟʂɟɧɢ ɧɚ: ɫɜɟɬɥɨʄɟɥɢʁɫɤɢ, ɯɪɨɦɨɮɢɥɧɢ, ɯɪɨɦɨɮɨɛɧɢ, ɄȻ ɫɚɛɢɪɧɨɝ ɬɭɛɭɥɚ ɢ ɛɟɧɢɝɧɟ ɨɧɤɨɰɢɬɨɦɟ. Ʉɥɚɫɢɮɢɤɚɰɢʁɚ ɄȻ ɫɟ ɭ ɜɟɥɢɤɨʁ ɦɟɪɢ ɡɚɫɧɢɜɚɥɚ ɧɚ ɧɚɥɚɡɭ ɫɜɟɬɥɨɫɧɟ ɦɢɤɪɨɫɤɨɩɢʁɟ, ɝɞɟ ɫɭ ɨɜɢ ɬɭɦɨɪɢ ɩɨɞɟʂɟɧɢ ɭ ɞɜɟ ɝɥɚɜɧɟ ɝɪɭɩɟ, ɤɚɨ ɬɭɦɨɪɢ ɤɨʁɢ ɩɨɫɟɞɭʁɭ ʁɚɫɧɭ ɫɜɟɬɥɨʄɟɥɢʁɫɤɭ ɢɥɢ ɧɟɫɜɟɬɥɨʄɟɥɢʁɫɤɭ „ɝɪɚɧɭɥɚɪɧɭ“ ɰɢɬɨɩɥɚɡɦɭ ɩɪɢ ɛɨʁɟʃɭ ɯɟɦɚɬɨɤɫɢɥɢɧ-ɟɨɡɢɧɨɦ4. Ɍɨɤɨɦ ɧɚɪɟɞɧɢɯ ɞɟɰɟɧɢʁɚ ɭɫɬɚɧɨɜʂɟɧɟ ɫɭ ɝɥɚɜɧɟ ɰɢɬɨɝɟɧɟɬɫɤɟ ɤɚɪɚɤɬɟɪɢɫɬɢɤɟ ɧɚʁɱɟɲʄɢɯ ɬɢɩɨɜɚ ɄȻ, ɲɬɨ ʁɟ ɩɨɬɜɪђɟɧɨ ɏɚʁɞɟɥɛɟɪɲɤɨɦ ɤɥɚɫɢɮɢɤɚɰɢʁɨɦ ɨɜɢɯ ɬɭɦɨɪɚ 1997. ɝɨɞɢɧɟ, ɤɨʁɚ ʁɟ ɛɢɥɚ ɨɫɧɨɜɚ ɡɚ ɤɥɚɫɢɮɢɤɚɰɢʁɭ ɄȻ ɨɞ ɫɬɪɚɧɟ ɋɜɟɬɫɤɟ ɡɞɪɚɜɫɬɜɟɧɟ ɨɪɝɚɧɢɡɚɰɢʁɟ 2004. ɝɨɞɢɧɟ5. ɍ ɫɤɨɪɢʁɟ ɜɪɟɦɟ ʁɟ ɩɨɤɚɡɚɧɨ ɞɚ ɩɨɫɬɨʁɢ ɫɬɪɨɝɚ ɤɨɪɟɥɚɰɢʁɚ ɢɡɦɟђɭ ɟɤɫɩɪɟɫɢʁɟ ɨɞɪɟђɟɧɢɯ ɝɟɧɚ ɢ ɩɨɞɬɢɩɨɜɚ ɄȻ, ɱɢɦɟ ʁɟ ɞɨɞɚɬɧɨ ɩɨɬɜɪђɟɧɚ ɢɞɟʁɚ ɞɚ ɩɨɞɬɢɩɨɜɢ ɄȻ ɩɪɟɞɫɬɚɜʂɚʁɭ ɪɚɡɥɢɱɢɬɟ ɛɢɨɥɨɲɤɟ ɟɧɬɢɬɟɬɟ6,7. ɍȼɈȾ 2 1.2. ȿɩɢɞɟɦɢɨɥɨɝɢʁɚ Ʉɚɪɰɢɧɨɦ ɛɭɛɪɟɝɚ (ɄȻ), ɱɢʁɢ ɫɭ ɪɚɧɢʁɢ ɧɚɡɢɜɢ ɛɢɥɢ: ɚɞɟɧɨɤɚɪɰɢɧɨɦ ɪɟɧɚɥɧɢɯ ɤɨɪɬɢɤɚɥɧɢɯ ʄɟɥɢʁɚ, ɯɢɩɟɪɧɟɮɪɨɦ, Grawitz ɬɭɦɨɪ, ɩɪɟɞɫɬɚɜʂɚ ɡɚʁɟɞɧɢɱɤɢ ɧɚɡɢɜ ɡɚ ɝɟɧɟɬɫɤɢ ɯɟɬɟɪɨɝɟɧɭ ɝɪɭɩɭ ɤɚɪɰɢɧɨɦɚ ɩɨɪɟɤɥɚ ɟɩɢɬɟɥɧɢɯ ʄɟɥɢʁɚ ɛɭɛɪɟɠɧɢɯ ɬɭɛɭɥɚ.Ɉɜɚ ɜɪɫɬɚ ɬɭɦɨɪɚ ɱɢɧɢ ɩɪɢɛɥɢɠɧɨ 3,8% ɨɞ ɭɤɭɩɧɨɝ ɛɪɨʁɚ ɦɚɥɢɝɧɢɬɟɬɚ ɤɨɞ ɨɞɪɚɫɥɢɯɢ 90-95% ɫɜɢɯ ɧɟɨɩɥɚɡɦɢ ɛɭɛɪɟɝɚ, ɱɢʁɢ ʁɟ ɛɢɨɥɨɲɤɢ ɩɨɬɟɧɰɢʁɚɥ ɜɢɫɨɤ ɢ ɱɟɫɬɨ ɫɚ ɮɚɬɚɥɧɢɦ ɢɫɯɨɞɨɦ8. Ʉɚɨ ɤɥɢɧɢɱɤɢ „ɧɟɦɢ“ ɦɚɥɢɝɧɢɬɟɬ ɩɪɟɞɫɬɚɜʂɚ ɜɟɥɢɤɢ ɫɜɟɬɫɤɢ ɡɞɪɚɜɫɬɜɟɧɢ ɩɪɨɛɥɟɦ ɱɢʁɚ ʁɟ ɢɧɰɢɞɟɧɰɚ ɭ ɤɨɧɫɬɚɧɬɧɨɦ ɩɨɪɚɫɬɭ ɩɨɫɥɟɞʃɢɯ 30 ɝɨɞɢɧɚ ɢ ɢɡɧɨɫɢ 2-4% ɧɚ ɝɨɞɢɲʃɟɦ ɧɢɜɨɭ, ɱɢɦɟ ɝɚ ɫɜɪɫɬɚɜɚ ɭ ɫɟɞɦɢ ɧɚʁɱɟɲʄɢ ɦɚɥɢɝɧɢ ɬɭɦɨɪ ɤɨɞ ɦɭɲɤɚɪɚɰɚ ɢ ɞɟɜɟɬɢ ɤɨɞ ɠɟɧɚ. ɍ ɩɨɪɟђɟʃɭ ɫɚ 1971. ɢɧɰɢɞɟɧɰɚ ɨɜɨɝ ɤɚɪɰɢɧɨɦɚ ʁɟ ɩɟɬ ɩɭɬɚ ɜɟʄɚ, ɫɚ ɞɜɨɫɬɪɭɤɨ ɜɟʄɨɦ ɫɦɪɬɧɨɲʄɭ9. Ɉɛʁɚɜʂɟɧɚ ɫɜɟɬɫɤɚ ɫɬɨɩɚ ɢɧɰɢɞɟɧɰɟ ɨɜɨɝ ɤɚɪɰɢɧɨɦɚ ɫɟ ɤɪɟʄɟ ɨɞ 0,6 ɞɨ 14,7 ɧɚ 100.000 ɫɬɚɧɨɜɧɢɤɚ, ɩɪɢ ɱɟɦɭ ɩɨɫɬɨʁɢ ɪɚɡɥɢɤɚ ɭ ɢɧɰɢɞɟɧɰɢ ɩɪɟɦɚ ɤɨɧɬɢɧɟɧɬɢɦɚ10. ɇɚʁɜɢɲɚ ɫɬɨɩɚ ɨɛɨʂɟɜɚʃɚ ʁɟ ɪɟɝɢɫɬɪɨɜɚɧɚ ɭ ȿɜɪɨɩɢ ɢ ɋɟɜɟɪɧɨʁ Ⱥɦɟɪɢɰɢ, ɚ ɧɚʁɧɢɠɚ ɭ Ⱥɡɢʁɢ ɢ ȳɭɠɧɨʁ Ⱥɦɟɪɢɰɢ. ɍ ȿɜɪɨɩɢ ɫɟ ɫɬɨɩɚ ɨɛɨʂɟɜɚʃɚ ɤɪɟʄɟ ɨɞ 2,9 ɧɚ 100.000 ɫɬɚɧɨɜɧɢɤɚ ɭ ɋɪɛɢʁɢ ɞɨ 15,2 ɧɚ 100.000 ɫɬɚɧɨɜɧɢɤɚ ɭ Ɋɟɩɭɛɥɢɰɢ ɑɟɲɤɨʁ11. Ɋɟɬɪɨɫɩɟɤɬɢɜɧɨɦ ɚɧɚɥɢɡɨɦ SEER (Surveillance Epidemiology End Results) ɛɚɡɟ ɩɨɞɚɬɚɤɚɡɚ ɩɟɪɢɨɞ ɨɞ 1975 ɞɨ 2006. пɨɤɚɡɚɧɨ ʁɟ ɞɚ ɫɬɨɩɚ ɢɧɰɢɞɟɧɰɟ ɨɛɨʂɟɜɚʃɚ ɨɞ ɄȻ ɭ ɋȺȾ ɭ ɞɚɬɨɦ ɩɟɪɢɨɞɭ ɩɨɪɚɫɥɚ ɫɚ 7,4 ɧɚ 17,6 ɧɚ 100.000 ɫɬɚɧɨɜɧɢɤɚ. ɍ ɋȺȾ ʁɟ ɬɨɤɨɦ 2011. ɪɟɝɢɫɬɪɨɜɚɧɨ 60.920 ɧɨɜɨɨɛɨɥɟɥɢɯ ɢ 13.120 ɫɦɪɬɧɢɯ ɢɫɯɨɞɚ ɨɞ ɄȻ, ɲɬɨ ʁɟ ɱɢɧɢɥɨ 2,3% ɨɞ ɭɤɭɩɧɨɝ ɛɪɨʁɚ ɫɦɪɬɧɢɯ ɢɫɯɨɞɚ ɨɞ ɫɜɢɯ ɤɚɪɰɢɧɨɦɚ12. Ɉɜɚʁ ɬɢɩ ɬɭɦɨɪɚ ɫɟ ɧɚʁɱɟɲʄɟ ʁɚɜʂɚ ɤɨɞ ɨɫɨɛɚ ɭ ɩɟɪɢɨɞɭ ɢɡɦɟђɭ ɩɟɬɟ ɢ ɫɟɞɦɟ ɞɟɰɟɧɢʁɟ ɠɢɜɨɬɚ, ɫɚ ɩɪɨɫɟɱɧɨɦ ɠɢɜɨɬɧɨɦ ɞɨɛɢ ɨɞ 66 ɝɨɞɢɧɚ ɭ ɜɪɟɦɟ ɞɢʁɚɝɧɨɡɟ ɢ 70 ɝɨɞɢɧɚ ɭ ɜɪɟɦɟ ɫɦɪɬɧɨɝ ɢɫɯɨɞɚ. ɂɧɰɢɞɟɧɰɚ ɨɛɨʂɟɜɚʃɚ ʁɟ ɞɜɚ ɞɨ ɬɪɢ ɩɭɬɚ ɜɟʄɚ ɤɨɞ ɨɫɨɛɚ ɦɭɲɤɨɝ ɩɨɥɚ ɢ ɧɟɲɬɨ ɜɟʄɚ ɤɨɞ ɨɫɨɛɚ ɰɪɧɟ ɪɚɫɟ13. Ɉɜɢ ɬɭɦɨɪɢ ɫɟ ɧɚʁɱɟɲʄɟ ɢɫɩɨʂɚɜɚʁɭ ɤɚɨ ɫɨɥɢɬɚɪɧɟ ɩɪɨɦɟɧɟ, ɦɨɝɭ ɛɢɬɢ ɦɭɥɬɢɮɨɤɚɥɧɢ ɭ 6-25% ɫɥɭɱɚʁɟɜɚ, ɚ ɤɚɨ ɛɢɥɚɬɟɪɚɥɧɢ ɬɭɦɨɪɢ ɫɟ ɞɢʁɚɝɧɨɫɬɢɤɭʁɭ ɤɨɞ 4% ɩɚɰɢʁɟɧɚɬɚ14. ɉɚɰɢʁɟɧɬɢ ɦɥɚђɢ ɨɞ 40 ɝɨɞɢɧɚ ɢɦɚʁɭ ɩɨɜɟʄɚɧ ɪɢɡɢɤ ɨɞ ɪɚɡɜɨʁɚ ɄȻ ɭ ɞɪɭɝɨɦ ɛɭɛɪɟɝɭ. Ⱦɨ 30% ɩɚɰɢʁɟɧɚɬɚ ɭ ɜɪɟɦɟ ɞɢʁɚɝɧɨɡɟ ɢɦɚ ɭɡɧɚɩɪɟɞɨɜɚɥɭ ɛɨɥɟɫɬ, ɚ ɨɤɨ 40% ɨɩɟɪɢɫɚɧɢɯ ɢɦɚ ɪɟɤɭɪɟɧɰɢʁɭ ɛɨɥɟɫɬɢ ɬɨɤɨɦ ɩɟɪɢɨɞɚ ɩɪɚʄɟʃɚ15. Ⱦɨɤɚɡɚɧɨ ʁɟ ɞɚ ɫɭ ɨɞɪɟђɟɧɟ ɝɟɧɟɬɫɤɟ ɩɪɨɦɟɧɟ ɩɨɜɟɡɚɧɟ ɫɚ ɩɨɜɟʄɚɧɨɦ ɢɧɰɢɞɟɧɰɨɦ ɨɛɨʂɟɜɚʃɚ ɨɞ ɄȻ. ɉɪɜɢ ɫɪɨɞɧɢɰɢ ɨɛɨɥɟɥɢɯ ɨɞ ɄȻ ɢɦɚʁɭ ɞɜɚ ɩɭɬɚ ɜɟʄɢ ɪɢɡɢɤ ɨɛɨʂɟɜɚʃɚ, ɩɪɢ ɱɟɦɭ ɮɚɦɢɥɢʁɚɪɧɟ ɮɨɪɦɟ ɛɨɥɟɫɬɢ ɱɢɧɟ ɦɚʃɟ ɨɞ 5% ɫɜɢɯ ɫɥɭɱɚʁɟɜɚ16. ɉɨɪɟɞ ɧɟɩɪɨɦɟɧʂɢɜɢɯ, ɢɧɞɟɧɬɢɮɢɤɨɜɚɧɚ ɫɭ ɬɪɢ ɧɚʁɱɟɲʄɚ ɩɪɨɦɟɧʂɢɜɚ ɮɚɤɬɨɪɚ ɪɢɡɢɤɚ ɡɚ ɧɚɫɬɚɧɚɤ ɄȻ: ɝɨʁɚɡɧɨɫɬ, ɩɭɲɟʃɟ ɢ ɚɪɬɟɪɢʁɫɤɚ ɯɢɩɟɪɬɟɧɡɢʁɚ, ɤɨʁɢ ɫɭ ɩɪɢɫɭɬɧɢ ɤɨɞ ɜɢɲɟ ɨɞ 50% ɨɛɨɥɟɥɢɯ11,17,18. Ɉɫɬɚɥɢ ɮɚɤɬɨɪɢ ɪɢɡɢɤɚ ɫɭ:ɭɩɨɬɪɟɛɚ ɞɢɭɪɟɬɢɤɚ, ɯɢɩɟɪɩɪɨɬɟɢɧɫɤɚ ɞɢʁɟɬɚ, ɫɬɟɱɟɧɚ ɰɢɫɬɢɱɧɚ ɛɨɥɟɫɬ ɛɭɛɪɟɝɚ (ɟɧɝɥ. ɫɤɪ. ACKD-acquired cystic kidney disease) ɤɨɞ ɛɨɥɟɫɧɢɤɚ ɧɚ ɯɟɦɨɞɢʁɚɥɢɡɢ, ɬɪɚɧɫɩɥɚɧɬɚɰɢʁɚ ɛɭɛɪɟɝɚ, ɏɂȼ ɢɧɮɟɤɰɢʁɚ, ɞɭɝɨɬɪɚʁɧɚ ɢɡɥɨɠɟɧɨɫɬ ɬɨɤɫɢɱɧɢɦ ɦɚɬɟɪɢʁɚɦɚ ɢ ʁɨɧɢɡɭʁɭʄɟɦ ɡɪɚɱɟʃɭ19,20, 21,22. ɍȼɈȾ 3 1.3. ɉɚɬɨɮɢɡɢɨɥɨɝɢʁɚ ɢ ɦɨɥɟɤɭɥɚɪɧɚ ɛɢɨɥɨɝɢʁɚ ɤɚɪɰɢɧɨɦɚ ɫɜɟɬɥɢɯ ʄɟɥɢʁɚ ɛɭɛɪɟɝɚ Ɂɧɚɱɚʁɚɧ ɧɚɩɪɟɞɚɤ ɭ ɪɚɡɭɦɟɜɚʃɭ ɛɢɨɥɨɝɢʁɟ ɫɄȻ ɩɨɫɬɢɝɧɭɬ ʁɟ 1993. ɝɨɞɢɧɟ ɨɬɤɪɢʄɟɦ von Hippel-Lindau (VHL) ɝɟɧɚ ɢ ɪɚɡɭɦɟɜɚʃɟɦ ʃɟɝɨɜɟ ɭɥɨɝɟ ɭ ɬɭɦɨɪɨɝɟɧɟɡɢ ɤɚɪɰɢɧɨɦɚ ɛɭɛɪɟɝɚ23. Ʉɚɪɰɢɧɨɦ ɛɭɛɪɟɝɚ ɫɟ ɦɨɠɟ ʁɚɜɢɬɢ ɤɚɨ ɮɚɦɢɥɢʁɚɪɧɚ ɢ ɫɩɨɪɚɞɢɱɧɚ ɮɨɪɦɚ ɛɨɥɟɫɬɢ. Ɏɚɦɢɥɢʁɚɪɧɚ ɮɨɪɦɚ ɫɄȻ ɭɞɪɭɠɟɧɚ ʁɟ ɫɚ VHL (ɟɧɝɥ. ɫɤɪ. von Hippel-Lindau) ɫɢɧɞɪɨɦɨɦ. Ɍɨ ʁɟ ɚɭɬɨɡɨɦɧɨ-ɞɨɦɢɧɚɧɬɧɢ ɧɚɫɥɟɞɧɢ ɩɨɪɟɦɟʄɚʁ ɤɨʁɢ ɫɟ ɦɚɧɢɮɟɫɬɭʁɟ ɪɚɡɜɨʁɟɦ: ɛɭɛɪɟɠɧɢɯ ɰɢɫɬɢ, ɪɟɬɢɧɚɥɧɢɯ ɯɟɦɚɧɝɢɨɦɚ, ɯɟɦɚɧɝɢɨɛɥɚɫɬɨɦɚ ɰɟɪɟɛɟɥɭɦɚ ɢ ɤɢɱɦɟɧɟ ɦɨɠɞɢɧɟ, ɮɟɨɯɪɨɦɨɰɢɬɨɦɚ, ɤɚɪɰɢɧɨɦɚ ɩɚɧɤɪɟɫɚ ɢ ɫɄȻ24. Ȼɨɥɟɫɬ ɢɡɚɡɢɜɚ ɦɭɬɚɰɢʁɚ VHL ɝɟɧɚ ɥɨɤɚɥɢɡɨɜɚɧɨɝ ɧɚ ɤɪɚɬɤɨɦ ɤɪɚɤɭ ɯɪɨɦɨɡɨɦɚ 3 (ɧɚ 3p25–p26 ɥɨɤɭɫɭ), ɤɨʁɢ ʁɟ ɬɭɦɨɪɫɤɢ ɫɭɩɪɟɫɨɪ ɝɟɧ25. Ɍɪɚɧɫɥɚɰɢʁɨɦ VHL ɝɟɧɚ ɧɚɫɬɚʁɟ VHL ɩɪɨɬɟɢɧ (pVHL) ɤɨʁɢ ɢɦɚ ɡɧɚɱɚʁɧɭ ɭɥɨɝɭ ɭ ʄɟɥɢʁɫɤɨɦ ɨɞɝɨɜɨɪɭ ɧɚ ɯɢɩɨɤɫɢʁɭ, ɤɨʁɢ ɨɫɬɜɚɪɭʁɟ ɩɨɫɪɟɞɫɬɜɨɦ ɯɢɩɨɤɫɢʁɨɦ ɢɧɞɭɤɨɜɚɧɨɝ ɮɚɤɬɨɪɚ (ɟɧɝɥ. ɫɤɪ. HIF-Hypoxia-Inducible Factor). Ɉɜɚʁ ɮɚɤɬɨɪ ɱɢɧɟ ɬɪɢ α-ɫɭɛʁɟɞɢɧɢɰɟ (HIF1α, HIF2α, HIF3α) ɢ ʁɟɞɧɚ β-ɫɭɛʁɟɞɢɧɢɰɚ (HIF1β)26. von Hippel-Lindau ɩɪɨɬɟɢɧ ɩɨɫɪɟɞɧɢɦ ɩɭɬɟɦ ɢɡɚɡɢɜɚ ɞɟɝɪɚɞɚɰɢʁɭ HIF1α27. Ɉɫɨɛɟ ɫɚ VHL ɫɢɧɞɪɨɦɨɦ ɫɟ ɪɚђɚʁɭ ɫɚ germ-line ɦɭɬɚɰɢʁɨɦ ɧɚ ʁɟɞɧɨɦ ɚɥɟɥɭ ɢ ɫɬɟɱɟɧɨɦ ɦɭɬɚɰɢʁɨɦ ɢɥɢ ɞɟɥɟɰɢʁɨɦ ɧɚ ɞɪɭɝɨɦ ɚɥɟɥɭ. Ʉɨɞ ɨɫɨɛɚ ɫɚ ɫɩɨɪɚɞɢɱɧɨɦ, ɧɟɧɚɫɥɟɞɧɨɦ ɮɨɪɦɨɦ ɫɄȻ, ɢɧɚɤɬɢɜɚɰɢʁɚ VHL ɝɟɧɚ ɩɭɬɟɦ ɦɟɬɢɥɚɰɢʁɟ ɢɥɢ ɞɟɥɟɰɢʁɟ ʁɚɜʂɚ ɫɟ ɤɨɞ 34% ɞɨ 60% ɫɥɭɱɚʁɟɜɚ, ɫɩɟɰɢɮɢɱɧɚ ʁɟ ɡɚ ɫɄȻ ɢ ɧɟ ɧɚɥɚɡɢ ɫɟ ɤɨɞ ɨɫɬɚɥɢɯ ɯɢɫɬɨɥɨɲɤɢɯ ɬɢɩɨɜɚ ɄȻ28. Ɇɭɬɚɰɢʁɚ ɨɜɨɝ ɝɟɧɚ ɞɨɜɨɞɢ ɞɨ ɫɬɜɚɪɚʃɚ ɞɢɫɮɭɧɤɰɢɨɧɚɥɧɨɝ pVHL, ɡɛɨɝ ɱɟɝɚ ɧɟ ɞɨɥɚɡɢ ɞɨ ɪɚɡɝɪɚɞʃɟ HIF1α, ɜɟʄ ɞɨ ʃɟɝɨɜɨɝ ɜɟɡɢɜɚʃɚ ɡɚ HIF1β ɢ ɫɬɜɚɪɚʃɚ ɯɟɬɟɪɨɞɢɦɟɪɧɨɝ ɬɪɚɧɫɤɪɢɩɰɢɨɧɨɝ ɮɚɤɬɨɪɚ ɤɨʁɢ ɦɢɝɪɢɪɚ ɭ ʄɟɥɢʁɫɤɨ ʁɟɞɪɨ. ɍ ʄɟɥɢʁɫɤɨɦ ʁɟɞɪɭ ɨɜɚʁ ɬɪɚɧɫɤɪɢɩɰɢɨɧɢ ɮɚɤɬɨɪ ɢɡɚɡɢɜɚ ɚɤɬɢɜɚɰɢʁɭ ɜɟʄɟɝ ɛɪɨʁɚ ɯɢɩɨɤɫɢʁɨɦ ɢɧɞɭɤɨɜɚɧɢɯ ɝɟɧɚ, ɩɪɢ ɱɟɦɭ ʁɟ ʁɟɞɚɧ ɨɞ ɧɚʁɡɧɚɱɚʁɧɢʁɢɯ ɜɚɫɤɭɥɚɪɧɢ ɟɧɞɨɬɟɥɧɢ ɮɚɤɬɨɪ ɪɚɫɬɚ (ɟɧɝɥ. ɫɤɪ. VEGF-vascular endothelial growth factor). Ɉɜɚʁ ɮɚɤɬɨɪ ɪɚɫɬɚ ɫɜɨʁɟ ɞɟʁɫɬɜɨ ɨɫɬɜɚɪɭʁɟ ɩɭɬɟɦ ɞɜɚ ɪɟɰɟɩɬɨɪɚ ɬɢɪɨɡɢɧ ɤɢɧɚɡɟ, VEGF-R1 ɢ VEGF-R2, ɤɨʁɢ ɫɟ ɧɚɥɚɡɟ ɧɚ ɜɚɫɤɭɥɚɪɧɢɦ ɟɧɞɨɬɟɥɧɢɦ ʄɟɥɢʁɚɦɚ, ɲɬɨ ɡɚ ɩɨɫɥɟɞɢɰɭ ɢɦɚ ʄɟɥɢʁɫɤɭ ɩɪɨɥɢɮɟɪɚɰɢʁɭ, ɚɧɝɢɨɝɟɧɟɡɭ ɢ ɫɦɚʃɟɧɭ ɚɩɨɩɬɨɡɭ29,30. Rivet ɫɚ ɫɚɪ. ʁɟ ɞɨɤɚɡɚɨ ɩɨɜɟʄɚɧɭ ɟɤɫɩɪɟɫɢʁɭ VEGF ɭ ɬɭɦɨɪɫɤɨɦ ɬɤɢɜɭ ɛɨɥɟɫɧɢɤɚ ɫɚ ɯɢɫɬɨɥɨɲɤɢ ɞɨɤɚɡɚɧɢɦ ɫɄȻɭ ɩɨɪɟђɟʃɭ ɫɚ ɧɟɬɭɦɨɪɫɤɢɦ ɬɤɢɜɨɦ, ɚ Schips ɫɚ ɫɚɪ. ɩɨɜɟʄɚɧ ɧɢɜɨ VEGF ɭ ɫɟɪɭɦɭ ɨɜɢɯ ɛɨɥɟɫɧɢɤɚ31,32. 1.4. ɉɨɞɟɥɚ ɤɚɪɰɢɧɨɦɚ ɛɭɛɪɟɝɚ Ʉɥɚɫɢɮɢɤɚɰɢʁɚ ɪɟɧɚɥɧɢɯ ɟɩɢɬɟɥɧɢɯ ɧɟɨɩɥɚɡɦɢ ɩɪɟɬɪɩɟɥɚ ʁɟ ɡɧɚɱɚʁɧɟ ɩɪɨɦɟɧɟ ɭ ɩɨɫɥɟɞʃɟ ɬɪɢ ɞɟɰɟɧɢʁɟ. Ɍɨɦɟ ʁɟ ɞɨɩɪɢɧɟɨ ɧɚɩɪɟɞɚɤ ɭ ɪɚɡɭɦɟɜɚʃɭ ɦɨɪɮɨɥɨɝɢʁɟ, ɢɦɭɧɨɯɢɫɬɨɯɟɦɢʁɟ, ɰɢɬɨɝɟɧɟɬɢɤɟ ɢ ɦɨɥɟɤɭɥɚɪɧɟ ɩɚɬɨɥɨɝɢʁɟ, ɲɬɨ ʁɟ ɪɟɡɭɥɬɨɜɚɥɨ ɭ ɩɪɟɩɨɡɧɚɜɚʃɭ ɧɨɜɢɯ ɬɭɦɨɪɫɤɢɯ ɟɧɬɢɬɟɬɚ33. Ⱦɜɟ ɡɧɚɱɚʁɧɟ ɫɜɟɬɫɤɟ ɤɨɧɫɟɧɡɭɫ ɤɨɧɮɟɪɟɧɰɢʁɟ ɨɞɪɠɚɧɟ ɭ ɏɚʁɞɟɥɛɟɪɝɭ 1996. ɢ Ɋɨɱɟɫɬɟɪɭ 1997., ɨɛɟɡɛɟɞɢɥɟ ɫɭ ɭ ɜɟɥɢɤɨʁ ɦɟɪɢ ɨɫɧɨɜɭ ɡɚ ɩɨɫɥɟɞʃɭ ɤɥɚɫɢɮɢɤɚɰɢʁɭ ɬɭɦɨɪɚ ɛɭɛɪɟɝɚ ɋɜɟɬɫɤɟ ɡɞɪɚɜɫɬɜɟɧɟ ɨɪɝɚɧɢɡɚɰɢʁɟ (ɋɁɈ) ɢɡ 200434,35. Ɉɜɨʁ ɍȼɈȾ 4 ɤɥɚɫɢɮɢɤɚɰɢʁɢ ʁɟ ɭ ɩɨɫɥɟɞʃɨʁ ɞɟɰɟɧɢʁɢ ɞɨɞɚɬɨ ɧɟɤɨɥɢɤɨ ɧɨɜɢɯ ɟɧɬɢɬɟɬɚ36. ɋɜɟɬɫɤɨ ɭɞɪɭɠɟʃɟ ɡɚ ɭɪɨɥɨɲɤɭ ɩɚɬɨɥɨɝɢʁɭ ʁɟ ɧɚ ɤɨɧɫɟɧɡɭɫ ɤɨɧɮɟɪɟɧɰɢʁɢ ɨɞɪɠɚɧɨʁ 2012. ɭ ȼɚɧɤɭɜɟɪɭ, ɞɚɥɨ ɩɪɟɩɨɪɭɤɟ ɡɚ ɩɪɨɦɟɧɭ ɢ ɩɨɛɨʂɲɚʃɟ ɩɨɫɬɨʁɟʄɟ ɤɥɚɫɢɮɢɤɚɰɢʁɟ ɬɭɦɨɪɚ ɛɭɛɪɟɝɚ37. ɍ ɬɚɛɟɥɢ ɛɪ. 1. ɧɚɜɟɞɟɧɚ ʁɟ ɤɥɚɫɢɮɢɤɚɰɢʁɚ ɄȻ ɩɪɟɦɚ ɋɁɈ ɢɡ 2004. ɢ ɢɧɰɢɞɟɧɰɚ ɩɨʁɟɞɢɧɢɯ ɬɢɩɨɜɚ35. Ɍɚɛɟɥɚ ɛɪ. 1. Кɥɚɫɢɮɢɤɚɰɢʁɚ ɢ ɢɧɰɢɞɟɧɰɚ ɤɚɪɰɢɧɨɦɚ ɛɭɛɪɟɝɚ ɩɪɟɦɚ ɋЗɈ (2004.) ɉɨɞɬɢɩɨɜɢ ɤɚɪɰɢɧɨɦɚ ɛɭɛɪɟɝɚ ɂɧɰɢɞɟɧɰɚ (%) Ʉɚɪɰɢɧɨɦ ɫɜɟɬɥɢɯ ʄɟɥɢʁɚ ɛɭɛɪɟɝɚ 75 ɉɚɩɢɥɚɪɧɢ ɤɚɪɰɢɧɨɦ ɛɭɛɪɟɝɚ 10 ɏɪɨɦɨɮɨɛɧɢ ɤɚɪɰɢɧɨɦ ɛɭɛɪɟɝɚ 5 Ʉɚɪɰɢɧɨɦ Ȼɟɥɢɧɢʁɟɜɢɯ ɫɚɛɢɪɧɢɯ ɤɚɧɚɥɢʄɚ ɛɭɛɪɟɝɚ 1 Ɇɟɞɭɥɚɪɧɢ ɤɚɪɰɢɧɨɦ ɛɭɛɪɟɝɚ <1 Ʉɚɪɰɢɧɨɦ ɛɭɛɪɟɝɚ ɭɞɪɭɠɟɧ ɫɚ ɧɟɭɪɨɛɥɚɫɬɨɦɨɦ <1 Бp11 ɬɪɚɧɫɥɨɤɚɰɢɨɧɢ ɤɚɪɰɢɧɨɦ ɛɭɛɪɟɝɚ <1 Ɇɭɰɢɧɨɡɧɢ ɬɭɛɭɥɚɪɧɢ ɢ ɤɚɪɰɢɧɨɦ ɜɪɟɬɟɧɚɫɬɢɯ ʄɟɥɢʁɚ ɛɭɛɪɟɝɚ <1 Ɇɭɥɬɢɥɨɤɭɥɚɪɧɢ ɰɢɫɬɢɱɧɢ ɤɚɪɰɢɧɨɦ ɛɭɛɪɟɝɚ <1 ɇɟɤɥɚɫɢɮɢɤɨɜɚɧɢ ɤɚɪɰɢɧɨɦ ɛɭɛɪɟɝɚ 5-10 ɍ ɬɚɛɟɥɢ ɛɪ. 2. ɧɚɜɟɞɟɧ ʁɟ ɩɪɟɞɥɨɝ ɧɨɜɢɯ ɩɨɞɬɢɩɨɜɚ ɄȻ, ɤɚɨ ɢ ɨɧɢɯ ɤɨʁɢ ɫɭ ɭ ɮɚɡɢ ɮɨɪɦɢɪɚʃɚ ɬʁ. ɩɪɢɜɪɟɦɟɧɢ ɬɭɦɨɪɫɤɢ ɟɧɬɢɬɟɬɢ ɩɪɟɦɚ ȼɚɧɤɭɜɟɪɫɤɨʁ ɤɥɚɫɢɮɢɤɚɰɢʁɢ37. Ɍɚɛɟɥɚ ɛɪ. 2. ɇɨɜɢ ɟɩɢɬɟɥɧɢ ɬɭɦɨɪɢ ɢ ɧɚɫɬɚʁɭʄɢ/ɩɪɢɜɪɟɦɟɧɢ ɬɭɦɨɪɫɤɢ ɟɧɬɢɬɟɬɢ ɩɪɟɦɚ ȼɚɧɤɭɜɟɪɫɤɨʁ ɤɥɚɫɢɮɢɤɚɰɢʁɢ ɇɨɜɢ ɟɩɢɬɟɥɧɢ ɬɭɦɨɪɢ Ɍɭɛɭɥɨɰɢɫɬɢɱɧɢ ɤɚɪɰɢɧɨɦ ɛɭɛɪɟɝɚ Ʉɚɪɰɢɧɨɦ ɛɭɛɪɟɝɚ ɭɞɪɭɠɟɧ ɫɚ ɫɬɟɱɟɧɨɦ ɰɢɫɬɢɱɧɨɦ ɛɨɥɟɫɬɢ ɋɜɟɬɥɨʄɟɥɢʁɫɤɢ (ɬɭɛɭɥɨ) ɩɚɩɢɥɚɪɧɢ ɤɚɪɰɢɧɨɦ ɛɭɛɪɟɝɚ MiT ɮɚɦɢɥɢʁɚ ɬɪɚɧɫɥɨɤɚɰɢɨɧɢɯ ɤɚɪɰɢɧɨɦɚ ɛɭɛɪɟɝɚ (ɭɤʂɭɱɭʁɭʄɢ t (6;11) ɤɚɪɰɢɧɨɦ ɛɭɛɪɟɝɚ) Ʉɚɪɰɢɧɨɦ ɛɭɛɪɟɝɚ ɭɞɪɭɠɟɧ ɫɚ ɫɢɧɞɪɨɦɨɦ ɧɚɫɥɟɞɧɟ ɥɟʁɨɦɢɨɦɚɬɨɡɟ ɇɚɫɬɚʁɭʄɢ/ɩɪɢɜɪɟɦɟɧɢ ɬɭɦɨɪɫɤɢ ɟɧɬɢɬɟɬɢ Ɍɢɪɟɨɢɞɟɢ-ɧɚɥɢɤ ɮɨɥɢɤɭɥɚɪɧɢ ɤɚɪɰɢɧɨɦɢ ɛɭɛɪɟɝɚ Ʉɚɪɰɢɧɨɦ ɛɭɛɪɟɝɚ ɭɞɪɭɠɟɧ ɫɚ ɧɟɞɨɫɬɚɬɤɨɦ ɫɭɤɰɢɧɢɱɧɟ Ȼ ɞɟɯɢɞɪɨɝɟɧɚɡɟ ALK-ɬɪɚɧɫɥɨɤɚɰɢɨɧɢ ɤɚɪɰɢɧɨɦɢ ɛɭɛɪɟɝɚ ɉɪɟɦɚ ɤɥɚɫɢɮɢɤɚɰɢʁɢ ɋɁɈ ɬɪɢ ɧɚʁɱɟɲʄɚ ɯɢɫɬɨɥɨɲɤɚ ɬɢɩɚ ɤɚɪɰɢɧɨɦɚ ɛɭɛɪɟɝɚ ɫɭ:  ɋɜɟɬɥɨʄɟɥɢʁɫɤɢ ɤɚɪɰɢɧɨɦ ɛɭɛɪɟɝɚ (ɫɄȻ)  ɉɚɩɢɥɚɪɧɢ ɤɚɪɰɢɧɨɦ ɛɭɛɪɟɝɚ (ɩɄȻ)  ɏɪɨɦɨɮɨɛɧɢ ɤɚɪɰɢɧɨɦ ɛɭɛɪɟɝɚ (ɯɄȻ) ɍȼɈȾ 5 1.4.1. Ʉɚɪɰɢɧɨɦ ɫɜɟɬɥɢɯ ʄɟɥɢʁɚ ɛɭɛɪɟɝɚ Ʉɚɪɰɢɧɨɦ ɫɜɟɬɥɢɯ ʄɟɥɢʁɚ ɛɭɛɪɟɝɚ ɢɥɢ ɫɜɟɬɥɨʄɟɥɢʁɫɤɢ ɤɚɪɰɢɧɨɦ ɛɭɛɪɟɝɚ (ɫɄȻ) ɩɪɟɞɫɬɚɜʂɚ ɧɚʁɱɟɲʄɢ ɯɢɫɬɨɥɨɲɤɢ ɬɢɩ, ɱɢɧɟʄɢ 80% ɫɜɢɯ ɤɚɪɰɢɧɨɦɚ ɛɭɛɪɟɝɚ. ɉɨ ɫɜɨɦ ɬɨɤɭʁɟ ɚɝɪɟɫɢɜɧɢʁɢ ɭ ɩɨɪɟђɟʃɭ ɫɚ ɩɚɩɢɥɚɪɧɢɦ ɢ ɯɪɨɦɨɮɨɛɧɢɦ ɩɨɞɬɢɩɨɦ ɢ ɨɞɝɨɜɨɪɚɧ ʁɟ ɡɚ ɧɚʁɜɟʄɢ ɛɪɨʁ ɫɦɪɬɧɢɯ ɢɫɯɨɞɚ ɢɡɚɡɜɚɧɢɯ ɤɚɪɰɢɧɨɦɨɦ ɛɭɛɪɟɝɚ. Ɉɜɚʁ ɬɢɩ ɬɭɦɨɪɚ ɫɟ ʁɚɜʂɚ ɤɚɨ ɫɩɨɪɚɞɢɱɧɚ ɮɨɪɦɚ (ɜɢɲɟ ɨɞ 96% ɫɥɭɱɚʁɟɜɚ) ɢ ɤɚɨ ɮɚɦɢɥɢʁɚɪɧɚ ɮɨɪɦɚ (ɦɚʃɟ ɨɞ 4%) ɬɭɦɨɪɚ38.ɋɤɨɪɨ ɫɜɟ ɮɚɦɢɥɢʁɚɪɧɟ ɮɨɪɦɟ ɩɨɫɥɟɞɢɰɚ ɫɭ ɧɚɫɥɟɞɧɟ ɦɭɬɚɰɢʁɟ VHL ɬɭɦɨɪ ɫɭɩɪɟɫɨɪ ɝɟɧɚ ɥɨɤɚɥɢɡɨɜɚɧɨɝ ɧɚ ɯɪɨɦɨɡɨɦɭ 3p, ɞɨɤ ɦɭɬɚɰɢʁɚ ɧɚ ɞɪɭɝɨɦ ɚɥɟɥɭ ɧɚɫɬɚʁɟ ɬɨɤɨɦ ɠɢɜɨɬɚ ɤɚɨ ɩɨɫɥɟɞɢɰɚ ɞɟɥɟɰɢʁɟ, ɯɢɩɟɪɦɟɬɢɥɚɰɢʁɟ ɢɥɢ ɪɟɚɪɚɧɠɦɚɧɚ39. ɂɧɚɤɬɢɜɚɰɢʁɚ VHL ɬɭɦɨɪ ɫɭɩɪɟɫɨɪ ɝɟɧɚ ʁɟ ɫɩɟɰɢɮɢɱɧɚ ɡɚ ɫɄȻ ɢ ɧɟ ɧɚɥɚɡɢ ɫɟ ɤɨɞ ɨɫɬɚɥɢɯ ɯɢɫɬɨɥɨɲɤɢɯ ɬɢɩɨɜɚ ɄȻ. Ɉɤɨ 2/3 ɨɫɨɛɚ ɫɚ ɫɩɨɪɚɞɢɱɧɢɦ ɨɛɥɢɤɨɦ ɬɭɦɨɪɚ ɢɦɚ ɛɢɚɥɟɥɧɭ ɢɧɚɤɬɢɜɚɰɢʁɭ VHL ɝɟɧɚ, ɞɨɤ ɨɫɬɚɥɢ ɩɨɤɚɡɭʁɭ ɩɨɢɧɬ ɦɭɬɚɰɢʁɭ ɢɥɢ ɯɢɩɟɪɦɟɬɢɥɚɰɢʁɭ ɩɪɨɦɨɬɨɪɚ ɭɞɪɭɠɟɧɭ ɫɚ ɬɪɚɧɫɤɪɢɩɰɢɨɧɨɦ ɢɧɚɤɬɢɜɚɰɢʁɨɦ. Ɉɫɬɚʁɟ ɧɟʁɚɫɧɨ ɞɚ ɥɢ ɩɨɫɬɨʁɟ ɨɛɥɢɰɢ ɫɄȻ ɫɚ ɮɭɧɤɰɢɨɧɚɥɧɢɦ VHL ɝɟɧɨɦ ɢɥɢ ʁɟ ɬɨ ɩɨɫɥɟɞɢɰɚ ɧɟɨɬɤɪɢɜɟɧɢɯ ɦɭɬɚɰɢʁɚ ɢ ɨɫɬɚɥɢɯ ɦɟɯɚɧɢɡɚɦɚ ɢɧɚɤɬɢɜɚɰɢʁɟ ɨɜɨɝ ɝɟɧɚ40,41. Ɇɚɤɪɨɫɤɨɩɫɤɢ ɨɜɢ ɬɭɦɨɪɢ ɫɭ ɞɨɛɪɨ ɨɝɪɚɧɢɱɟɧɢ, ɦɚɞɚ ɜɟɥɢɤɢ ɬɭɦɨɪɢ ɩɨɤɚɡɭʁɭ ɢɧɮɢɥɬɪɚɬɢɜɧɢ ɪɚɫɬ ɢ ɱɟɲʄɟ ɧɟɦɚʁɭ ɤɚɩɫɭɥɭ. ɇɚ ɩɪɟɫɟɤɭ ɫɭ ɡɥɚɬɧɨ-ɠɭɬɟ ɛɨʁɟ, ɫɚ ɱɟɫɬɢɦ ɩɨʂɢɦɚ ɧɟɤɪɨɡɟ ɢ ɯɟɦɨɪɚɝɢʁɟ. ɏɢɫɬɨɥɨɲɤɢ ɦɨɝɭ ɩɨɤɚɡɢɜɚɬɢ ɚɥɜɟɨɥɚɪɧɢ, ɫɨɥɢɞɧɢ, ɰɢɫɬɢɱɧɢ ɢ ɬɭɛɭɥɚɪɧɢ ɨɛɥɢɤ. ȶɟɥɢʁɟ ɫɭ ɭɧɢɮɨɪɦɧɟ, ɫɚ ɢɡɪɚɠɟɧɨɦ ɫɜɟɬɥɨɦ ɰɢɬɨɩɥɚɡɦɨɦ ɛɨɝɚɬɨɦ ɭ ɝɥɢɤɨɝɟɧɭ ɢ ɦɚɫɬɢɦɚ. Ɉɜɚɤɚɜ ɢɡɝɥɟɞ ɰɢɬɨɩɥɚɡɦɟ ʁɟ ɤɚɪɚɤɬɟɪɢɫɬɢɱɚɧ ɡɚ ɬɭɦɨɪɟ ɫɚ ɧɢɫɤɢɦ ɦɚɥɢɝɧɢɬɟɬɨɦ, ɞɨɤ ɫɟ ɤɨɞ ɨɛɥɢɤɚ ɫɚ ɜɢɲɢɦ ɫɬɟɩɟɧɨɦ ɦɚɥɢɝɧɢɬɟɬɚ ɜɢɞɢ ɝɪɚɧɭɥɢɪɚɧɚ ɰɢɬɨɩɥɚɡɦɚ42. ɂɦɭɧɨɯɢɫɬɨɯɟɦɢʁɫɤɢ, ɧɟɨɩɥɚɫɬɢɱɧɟ ʄɟɥɢʁɟ ɩɨɤɚɡɭʁɭ ɩɨɡɢɬɢɜɧɨɫɬ ɧɚ ɜɢɦɟɧɬɢɧ, ɭɝʂɟɧɭ ɚɧɯɢɞɪɚɡɭ 9 (CA9), ɦɚɪɤɟɪ ɤɚɪɰɢɧɨɦɚ ɛɭɛɪɟɝɚ (RCCMa), CD10, PAX2 ɢ PAX8, ɚ ɨɛɢɱɧɨ ɫɭ ɧɟɝɚɬɢɜɧɟ ɢɥɢ ɮɨɤɚɥɧɨ ɩɨɡɢɬɢɜɧɟ ɧɚ ɰɢɬɨɤɟɪɚɬɢɧ 7 (CK7), ȿ-ɤɚɞɯɟɪɢɧ ɢ ɤɚɞɯɟɪɢɧ ɫɩɟɰɢɮɢɱɚɧ ɡɚ ɛɭɛɪɟɝ43. Ʉɚɪɰɢɧɨɦ ɫɜɟɬɥɢɯ ʄɟɥɢʁɚ ɛɭɛɪɟɝɚ ɦɧɨɝɨ ɱɟɲʄɟ ɩɨɤɚɡɭʁɟ ɜɢɫɨɤɭ ɟɤɫɩɪɟɫɢʁɭ CA9 ɭ ɩɨɪɟђɟʃɭ ɫɚ ɨɫɬɚɥɢɦ ɬɢɩɨɜɢɦɚ ɤɚɪɰɢɧɨɦɚ ɛɭɛɪɟɝɚ44. ɉɨɪɟɞ ɫɬɚɧɞɚɪɞɧɢɯ ɢɦɭɧɨɯɢɫɬɨɯɟɦɢʁɫɤɢɯ ɦɚɪɤɟɪɚ, ɭ ɞɢʁɚɝɧɨɡɢ ɫɄȻ ɡɧɚɱɚʁɧɭ ɭɥɨɝɭ ɢɦɚʁɭ ʁɨɲ ɞɜɚ ɦɚɪɤɟɪɚ: ɯɭɦɚɧɢ ɩɪɨɬɟɢɧ ɨɲɬɟʄɟʃɚ ɛɭɛɪɟɝɚ (ɟɧɝɥ. ɫɤɪ. hKIM-1-human kidney injury molecul-1) ɢ ɚɤɜɚɩɨɪɢɧ 1(AQP-1)45,46. ɏɭɦɚɧɢ ɩɪɨɬɟɢɧ ɨɲɬɟʄɟʃɚ ɛɭɛɪɟɝɚ (hKIM-1) ʁɟ ɬɢɩ 1 ɬɪɚɧɫɦɟɦɛɪɚɧɫɤɨɝ ɩɪɨɬɟɢɧɚ ɤɨʁɢ ɩɪɟɞɫɬɚɜʂɚ ɫɟɧɡɢɬɢɜɚɧ ɢ ɫɩɟɰɢɮɢɱɚɧ ɛɢɨɦɚɪɤɟɪ ɩɪɨɤɫɢɦɚɥɧɢɯ ɪɟɧɚɥɧɢɯ ɬɭɛɭɥɚɪɧɢɯ ʄɟɥɢʁɚ ɤɨʁɟ ɫɟ ɧɚɥɚɡɟ ɭ ɩɪɨɰɟɫɭ ɨɩɨɪɚɜɤɚ ɧɚɤɨɧ ɢɫɯɟɦɢʁɫɤɨɝ ɢɥɢ ɬɨɤɫɢɱɧɨɝ ɨɲɬɟʄɟʃɚ45. Ⱦɨɤɚɡɚɧɚ ʁɟ ɜɢɫɨɤɚ ɟɤɫɩɪɟɫɢʁɚ hKIM-1 ɭ ɬɭɦɨɪɫɤɨɦ ɬɤɢɜɭ ɛɨɥɟɫɧɢɤɚ ɫɚ ɫɄȻ. ɍ ɫɬɭɞɢʁɢ ɭ ɤɨʁɨʁ ɫɭ ɚɧɚɥɢɡɢɪɚɧɚ 264 ɬɤɢɜɧɚ ɭɡɨɪɤɚ ɪɟɧɚɥɧɢɯ ɟɩɢɬɟɥɧɢɯ ɬɭɦɨɪɚ ɢ 221 ɬɤɢɜɧɢ ɭɡɨɪɚɤ ɧɟɪɟɧɚɥɧɢɯ ɬɭɦɨɪɚ, ɩɨɤɚɡɚɧɚ ʁɟ ɜɢɫɨɤɚ ɟɤɫɩɪɟɫɢʁɚ ɨɜɨɝ ɛɢɨɦɚɪɤɟɪɚ ɤɨɞ ɫɄȻ (74%), ɩɚɩɢɥɚɪɧɨɝ ɄȻ (94%) ɢ ɦɟɬɚɫɬɚɬɫɤɨɝ ɄȻ (78%). ɂɦɭɧɨɪɟɚɤɬɢɜɧɨɫɬ ɧɢʁɟ ɞɟɬɟɤɬɨɜɚɧɚ ɤɨɞ ɯɪɨɦɨɮɨɛɧɨɝ ɄȻ (ɯɄȻ), ɚ ɞɟɬɟɤɬɨɜɚɧɚ ʁɟ ɜɟɨɦɚ ɧɢɫɤɨɝ ɢɧɬɟɧɡɢɬɟɬɚ ɤɨɞ ɨɧɤɨɰɢɬɨɦɚ (9,75%). ɍ ɝɪɭɩɢ ɧɟɪɟɧɚɥɧɢɯ ɬɤɢɜɧɢɯ ɭɡɨɪɚɤɚ, ɢɦɭɧɨɪɟɚɤɬɢɜɧɨɫɬ ʁɟ ɢɡɧɨɫɢɥɚ 11,8%, ɫɚ ɍȼɈȾ 6 ɧɚʁɜɟʄɨɦ ɟɤɫɩɪɟɫɢʁɨɦ (93,8%) ɤɨɞ ɫɜɟɬɥɨʄɟɥɢʁɫɤɨɝ ɤɚɪɰɢɧɨɦɚ ʁɚʁɧɢɤɚ. ɇɚ ɨɫɧɨɜɭ ɪɟɡɭɥɬɚɬɚ ɧɚɜɟɞɟɧɟ ɫɬɭɞɢʁɟ, ɡɚɤʂɭɱɟɧɨ ʁɟ ɞɚ hKIM-1 ɩɪɟɞɫɬɚɜʂɚ ɪɟɥɚɬɢɜɧɨ ɫɩɟɰɢɮɢɱɚɧ ɢ ɫɟɧɡɢɬɢɜɚɧ ɦɚɪɤɟɪ ɡɚ ɩɨɬɜɪɞɭ ɞɢʁɚɝɧɨɡɟ ɫɄȻ, ɩɄȻ, ɪɚɡɥɢɤɨɜɚʃɟ ɫɄȻ ɨɞ ɯɄȻ ɢ ɨɧɤɨɰɢɬɨɦɚ, ɤɚɨ ɢ ɞɢʁɚɝɧɨɡɭ ɤɚɪɰɢɧɨɦɚ ɫɜɟɬɥɢɯ ʄɟɥɢʁɚ ɨɜɚɪɢʁɭɦɚ47. ɋɜɟɬɥɨʄɟɥɢʁɫɤɢ ɤɚɪɰɢɧɨɦ ɛɭɛɪɟɝɚ ɩɪɟɞɫɬɚɜʂɚ ʁɟɞɚɧ ɨɞ ɧɚʁɱɟɲʄɢɯ ɦɢɦɢɤɪɢʁɫɤɢɯ ɬɭɦɨɪɚ ɭ ɯɢɪɭɪɲɤɨʁ ɩɚɬɨɥɨɝɢʁɢ. Ɍɟɨɪɟɬɫɤɢ, ɦɨɠɟ ɞɚɬɢ ɦɟɬɚɫɬɚɡɟ ɭ ɛɢɥɨ ɤɨɦ ɞɟɥɭ ɬɟɥɚ, ɩɪɢ ɱɟɦɭ ɩɨɤɚɡɭʁɟ ɡɧɚɱɚʁɧɨ ɦɨɪɮɨɥɨɲɤɨ ɩɪɟɤɥɚɩɚʃɟ ɫɚ ɞɪɭɝɢɦ ɧɟɛɭɛɪɟɠɧɢɦ ɧɟɨɩɥɚɡɦɚɦɚ ɢ ɧɨɪɦɚɥɧɢɦ ɬɤɢɜɢɦɚ. ɍ ɬɢɦ ɫɥɭɱɚʁɟɜɢɦɚ, ɫɩɟɰɢɮɢɱɧɢ ɢɦɭɧɨɯɢɫɬɨɯɟɦɢʁɫɤɢ ɦɚɪɤɟɪɢ ɢɦɚʁɭ ɡɧɚɱɚʁɧɭ ɞɢʁɚɝɧɨɫɬɢɱɤɭ ɭɥɨɝɭ. ɇɨɜɢʁɟ ɫɬɭɞɢʁɟ ɭɤɚɡɭʁɭ ɞɚ ɦɚɪɤɟɪɢ ɤɚɨ ɲɬɨ ɫɭ PAX2, PAX8 ɢ hKIM-1, ɩɪɟɞɫɬɚɜʂɚʁɭ ɡɧɚɱɚʁɧɨ ɫɟɧɡɢɬɢɜɧɢʁɟ ɢ ɫɩɟɰɢɮɢɱɧɢʁɟ ɦɚɪɤɟɪɟ ɡɚ ɞɢʁɚɝɧɨɡɭ ɦɟɬɚɫɬɚɬɫɤɨɝ ɫɄȻ ɭ ɩɨɪɟђɟʃɭ ɫɚ CD10 ɢ RCCMa48. Ⱥɤɜɚɩɨɪɢɧ 1(AQP-1) ʁɟ ʁɟɞɚɧ ɨɞ ɬɪɚɧɫɩɨɪɬɧɢɯ ɩɪɨɬɟɢɧɚ ɡɚ ɜɨɞɭ ɤɨʁɢ ɫɟ ɟɤɩɪɢɦɢɪɚ ɧɚ ɦɧɨɝɢɦ ɟɩɢɬɟɥɧɢɦ ɬɤɢɜɢɦɚ, ɭɤʂɭɱɭʁɭʄɢ ɢ ɩɪɨɤɫɢɦɚɥɧɢ ɬɭɛɭɥ ɛɭɛɪɟɝɚ. ɂɦɭɧɨɯɢɫɬɨɯɟɦɢʁɫɤɚ ɢɫɩɢɬɢɜɚʃɚ ɫɭ ɩɨɤɚɡɚɥɚ ɞɚ AQP-1 ɩɪɟɞɫɬɚɜʂɚ ɜɢɫɨɤɨɫɩɟɰɢɮɢɱɚɧ ɦɚɪɤɟɪ ɡɚ ɞɢʁɚɝɧɨɡɭ ɢ ɩɪɨɝɧɨɡɭ ɨɛɨɥɟɥɢɯ ɨɞɫɄȻ. Mazal ɢ ɫɚɪ.ɫɭ ɩɨɪɟɞɢɥɢ ɟɤɫɩɪɟɫɢʁɭ AQP- 1, AQP-2 ɢPAX-2 ɫɚ ɫɬɚɧɞɚɪɞɧɢɦ ɦɚɪɤɟɪɢɦɚ, CD10 ɢ ɰɢɬɨɤɟɪɚɬɢɧɨɦ 7 (CK7), ɧɚ 202 ɬɤɢɜɧɚ ɭɡɨɪɤɚ ɬɭɦɨɪɚ ɛɭɛɪɟɝɚ ɤɨʁɟ ɫɭ ɱɢɧɢɥɢ ɪɚɡɥɢɱɢɬɢ ɬɢɩɨɜɢ ɤɚɪɰɢɧɨɦɚ ɛɭɛɪɟɝɚ ɢ ɨɧɤɨɰɢɬɨɦɢ. ɇɚђɟɧɚ ʁɟ ɜɢɫɨɤɚ ɟɤɫɩɪɟɫɢʁɚ AQP-1 ɤɨɞ ɫɄȻ (78%) ɢ ɩɄȻ (75%), ɚɥɢ ɧɢʁɟ ɧɚђɟɧɚ ʃɟɝɨɜɚ ɟɤɫɩɪɟɫɢʁɚ ɤɨɞ ɯɄȻ ɢ ɨɧɤɨɰɢɬɨɦɚ. ɍɬɜɪђɟɧɚ ʁɟ ɢɧɜɟɪɡɧɚ ɟɤɫɩɪɟɫɢʁɚ AQP-1 ɢ PAX-2 ɫɚ ɧɭɤɥɟɪɧɢɦ ɝɪɚɞɭɫɨɦ ɫɄȻ, ɚ ɧɢʁɟ ɛɢɥɨ ɤɨɪɟɥɚɰɢʁɟ ɫɚ ɫɬɚɞɢʁɭɦɨɦ ɬɭɦɨɪɚ. Ɂɚɤʂɭɱɟɧɨ ʁɟ ɞɚ AQP-1 ɢ PAX-2 ɩɪɟɞɫɬɚɜʂɚʁɭ ɩɨɭɡɞɚɧɟ ɦɚɪɤɟɪɟ ɡɚ ɞɢʁɚɝɧɨɡɭ ɫɄȻ ɧɢɠɟɝ ɧɭɤɥɟɚɪɧɨɝ ɝɪɚɞɭɫɚ (1 ɢ 2 ɩɨ Fuhrman-ɭ), ɚɥɢ ɧɟ ɢ ɜɢɲɟɝ (3 ɢ 4 ɩɨ Fuhrman-ɭ)46. ɉɪɟɦɚ ȼɨɞɢɱɭ ɚɦɟɪɢɱɤɨɝ ɭɞɪɭɠɟʃɚ ɭɪɨɥɨɝɚ, ɧɟɡɚɜɢɫɧɢ ɩɨɪɟɞɢɤɬɨɪɢ ɩɪɟɠɢɜʂɚɜɚʃɚ ɨɛɨɥɟɥɢɯ ɨɞ ɫɄȻ ɫɭ: Fuhrman-ɨɜ ɧɭɤɥɟɚɪɧɢ ɝɪɚɞɭɫ, ɜɟɥɢɱɢɧɚ ɬɭɦɨɪɚ, ɩɪɢɫɭɫɬɜɨ ɬɭɦɨɪɫɤɟ ɧɟɤɪɨɡɟ, ɦɢɤɪɨɜɚɫɤɭɥɚɪɧɚ ɢɧɜɚɡɢʁɚ, ɫɚɪɤɨɦɚɬɨɢɞɧɟ ɩɪɨɦɟɧɟ ɢ ɡɚɯɜɚɬɚʃɟ ɫɚɛɢɪɧɨɝ ɫɢɫɬɟɦɚ49. 1.4.2.ɉɚɩɢɥɚɪɧɢ ɤɚɪɰɢɧɨɦ ɛɭɛɪɟɝɚ ɉɚɩɢɥɚɪɧɢ ɤɚɪɰɢɧɨɦ ɛɭɛɪɟɝɚ (ɩɄȻ) ʁɟ ɞɪɭɝɢ ɧɚʁɱɟɲʄɢ ɯɢɫɬɨɥɨɲɤɢ ɬɢɩ ɤɚɪɰɢɧɨɦɚ ɛɭɛɪɟɝɚ, ɱɢɧɟʄɢ 10-15% ɫɜɢɯ ɛɭɛɪɟɠɧɢɯ ɧɟɨɩɥɚɡɦɢ. ɉɨɫɬɨʁɟ ɞɜɚ ɬɢɩɚ ɩɄȻ, ɬɢɩ 1 ɢ ɬɢɩ 2, ɤɨʁɢ ɫɟ ɪɚɡɥɢɤɭʁɭ ɩɨ ɯɢɫɬɨɦɨɪɮɨɥɨɲɤɢɦ ɤɚɪɚɤɬɟɪɢɫɬɢɤɚɦɚ, ɝɟɧɫɤɨʁ ɚɥɬɟɪɚɰɢʁɢ ɢ ɩɪɨɝɧɨɡɢ. Ɉɛɚ ɬɢɩɚ ɫɟ ɦɨɝɭ ʁɚɜʂɚɬɢ ɤɚɨ ɧɚɫɥɟɞɧɟ ɢ ɫɩɨɪɚɞɢɱɧɟ ɮɨɪɦɟ50. ɇɚɫɬɚɧɚɤ ɩɄȻ ʁɟ ɧɚʁɱɟɲʄɟ ɭɞɪɭɠɟɧ ɫɚ ɬɪɢɡɨɦɢʁɨɦ/ɬɟɬɪɚɡɨɦɢʁɨɦ ɯɪɨɦɨɡɨɦɚ 7, ɬɪɢɡɨɦɢʁɨɦ ɯɪɨɦɨɡɨɦɚ 12, 16, 17 ɢ/ɢɥɢ 20 ɢ ɝɭɛɢɬɤɨɦ Y ɯɪɨɦɨɡɨɦɚ51. Ɇɢɤɪɨɫɤɨɩɫɤɢ, ɩɄȻ ɫɭ ɞɨɛɪɨ ɨɝɪɚɧɢɱɟɧɢ ɬɭɦɨɪɢ ɤɨʁɢ ɦɨɝɭ ɢɦɚɬɢ ɩɫɟɭɞɨɤɚɩɫɭɥɭ. ɇɚ ɩɪɟɫɟɤɭ ɫɭ ɠɭɬɟ ɢɥɢ ɛɪɚɨɧ ɛɨʁɟ ɭ ɡɚɜɢɫɧɨɫɬɢ ɨɞ ɩɪɟɞɨɦɢɧɚɰɢʁɟ ɩɟɧɭɲɚɜɢɯ ɦɚɤɪɨɮɚɝɚ ɢɥɢ ɯɟɦɨɪɚɝɢʁɟ. Ɇɢɤɪɨɫɤɨɩɫɤɢ, ɬɢɩ 1 ɨɜɢɯ ɬɭɦɨɪɚ ɱɢɧɟ ɦɚɥɟ ɧɟɨɩɥɚɫɬɢɱɧɟ ʄɟɥɢʁɟ ɫɚ ɨɫɤɭɞɧɨɦ ɛɚɡɨɮɢɥɧɨɦ ɰɢɬɨɩɥɚɡɦɨɦ ɢ ɧɢɫɤɨɝ ɫɭ ɧɭɤɥɟɚɪɧɨɝ ɝɪɚɞɭɫɚ. Ɍɢɩ 2 ɫɟ ɫɚɫɬɨʁɢ ɨɞ ɤɨɥɭɦɧɚɪɧɢɯ ʄɟɥɢʁɚ ɫɚ ɟɨɡɢɧɨɮɢɥɧɨɦ ɰɢɬɨɩɥɚɡɦɨɦ ɢ ɜɢɫɨɤɢɦ ɧɭɤɥɚɪɧɢɦ ɝɪɚɞɭɫɨɦ. Ʉɨɞ ɨɜɨɝ ɬɢɩɚ ɫɟ ɱɟɫɬɨ ɜɢђɚ ɍȼɈȾ 7 ɩɫɟɭɞɨɫɬɪɚɬɢɮɢɤɚɰɢʁɚ, ɤɨʁɚ ʁɟ ɨɞɫɭɬɧɚ ɤɨɞ ɬɢɩɚ 152. ɂɦɭɧɨɯɢɫɬɨɯɟɦɢʁɫɤɢ, ɩɄȻ ɤɚɪɚɤɬɟɪɢɲɟ ɩɨɡɢɬɢɜɧɨɫɬ ɧɚ ɰɢɬɨɤɟɪɚɬɢɧ CK7, ɱɟɲʄɟ ɤɨɞ ɬɢɩɚ 1, ɤɚɨ ɢ ɧɚ AMACR, CD10, RCCMa, PAX-2 ɢ PAX846. ɉɪɨɝɧɨɡɚ ɨɜɨɝ ɬɭɦɨɪɚ ɡɚɜɢɫɢ ɨɞ ɧɭɤɥɟɪɧɨɝ ɝɪɚɞɭɫɚ, ɫɬɚɞɢʁɭɦɚ ɢ ɩɪɢɫɭɫɬɜɚ ɫɚɪɤɨɦɚɬɨɢɞɧɢɯ ɩɪɨɦɟɧɚ. 1.4.3. ɏɪɨɦɨɮɨɛɧɢ ɤɚɪɰɢɧɨɦ ɛɭɛɪɟɝɚ ɏɪɨɦɨɮɨɛɧɢ ɤɚɪɰɢɧɨɦ ɛɭɛɪɟɝɚ (ɯɄȻ) ʁɟ ɬɪɟʄɢ ɧɚʁɱɟɲʄɢ ɬɢɩ, ɤɨʁɢ ɱɢɧɢ ɨɤɨ 5% ɫɜɢɯ ɤɚɪɰɢɧɨɦɚ ɛɭɛɪɟɝɚ53. ɇɚɡɢɜ ʁɟ ɞɨɛɢɨ ɡɛɨɝ ɩɪɨɡɪɚɱɧɨɝ ɢɡɝɥɟɞɚ ʄɟɥɢʁɚ ɩɪɢ ɛɨʁɟʃɭ ɯɟɦɚɬɨɤɫɢɥɢɧ-ɟɨɡɢɧɨɦ. ɇɚɫɬɚʁɟ ɤɚɨ ɩɨɫɥɟɞɢɰɚ ɯɢɩɥɨɞɢɩɥɨɢɞɢʁɟ ɢ ɝɭɛɢɬɤɚ ɯɪɨɦɨɡɨɦɚ 1, 2, 6, 10, 13, 17 ɢ 2154. ɏɟɪɟɞɢɬɚɪɧɚ ɮɨɪɦɚ ɨɜɨɝ ɬɭɦɨɪɚ ʁɚɜʂɚ ɫɟ ɭ ɫɤɥɨɩɭ BHD ɫɢɧɞɪɨɦɚ (ɟɧɝɥ. ɫɤɪ. Birt-Hogg-Dube’) ɤɨʁɢ ɧɚɫɬɚʁɟ ɤɚɨ ɩɨɫɥɟɞɢɰɚ germline ɦɭɬɚɰɢʁɟ ɝɟɧɚ ɡɚ ɮɨɥɢɤɭɥɢɧ, ɥɨɰɢɪɚɧɨɝ ɧɚ ɯɪɨɦɨɡɨɦɭ 17p11.255. Ɇɚɤɪɨɫɤɨɩɫɤɢ ɨɜɢ ɬɭɦɨɪɢ ɫɭ ɞɨɛɪɨ ɞɟɦɚɪɤɢɪɚɧɢ ɨɞ ɨɤɨɥɧɨɝ ɬɤɢɜɚ ɢ ɧɟɦɚʁɭ ɤɚɩɫɭɥɭ. ɇɚ ɩɪɟɫɟɤɭ ɫɭ ɫɦɟђɟ ɢɥɢ ɫɜɟɬɥɟɛɨʁɟ. Ɇɢɤɪɨɫɤɨɩɫɤɢ, ɨɜɢ ɬɭɦɨɪɢ ɫɟ ɦɨɝɭ ɩɨɞɟɥɢɬɢ ɭ ɞɜɟ ɤɚɬɟɝɨɪɢʁɟ. ɍ ɬɢɩɢɱɧɨʁ ɜɚɪɢʁɚɧɬɢ ɬɭɦɨɪɫɤɟ ʄɟɥɢʁɟ ɫɟ ɩɪɟɞɨɦɢɧɚɧɬɧɨ ɫɚɫɬɨʁɟ ɨɞ ɛɥɟɞɢɯ ʄɟɥɢʁɚ ɫɚ ɮɢɧɨɦ ɪɟɬɢɤɭɥɚɪɧɨɦ ɰɢɬɨɩɥɚɡɦɨɦ ɢ ʁɚɫɧɨ ɨɝɪɚɧɢɱɟɧɨɦ ʄɟɥɢʁɫɤɨɦ ɝɪɚɧɢɰɨɦ. ɍ ɟɨɡɢɧɨɮɢɥɧɨʁ ɜɚɪɢʁɚɧɬɢ, ɩɪɟɞɨɦɢɧɚɧɬɧɟ ɫɭ ɟɨɡɢɧɨɮɢɥɧɟ ʄɟɥɢʁɟ ɢ ɱɢɧɟ ɜɢɲɟ ɨɞ 80% ʄɟɥɢʁɚ. Ɇɟɦɛɪɚɧɚ ʁɟɞɪɚ ʁɟ ɧɟɩɪɚɜɢɥɧɚ, ɚ ɱɟɫɬɨ ɫɟ ɜɢɞɢ ɛɢɧɭɤɥɟɚɰɢʁɚ ɢ ɩɟɪɢɧɭɤɥɟɚɪɧɢ ɯɚɥɨɨ56.ɂɦɭɧɨɯɢɫɬɨɯɟɦɢʁɫɤɢ, ɬɭɦɨɪɫɤɟ ʄɟɥɢʁɟ ɩɨɤɚɡɭʁɭ ɞɢɮɭɡɧɭ ɦɟɦɛɪɚɧɫɤɭ ɩɨɡɢɬɢɜɧɨɫɬ ɧɚCK7, CD82, ɩɚɥɜɚɥɛɭɦɢɧ, CD117, ȿ-ɤɚɞɯɟɪɢɧ, ɚ ɧɟɝɚɬɢɜɧɨɫɬ ɧɚ CA9, CD10 ɢ RCCMa57,58.Ɉɜɚʁ ɬɢɩ ɬɭɦɨɪɚ ɤɚɪɚɤɬɟɪɢɲɟ ɫɩɨɪɢ ɪɚɫɬ ɢ ɞɨɛɪɚ ɩɪɨɝɧɨɡɚ, ɦɚɞɚ ɬɭɦɨɪɢ ɫɚ ɫɚɪɤɨɦɚɬɨɢɞɧɢɦ ɩɪɨɦɟɧɚɦɚ ɢ ɟɤɫɬɟɧɡɢɜɧɨɦ ɧɟɤɪɨɡɨɦ ɦɨɝɭ ɩɨɤɚɡɢɜɚɬɢ ɚɝɪɟɫɢɜɚɧ ɤɥɢɧɢɱɤɢ ɬɨɤ59. 1.4.4. Ɇɭɥɬɢɥɨɤɭɥɚɪɧɢ ɰɢɫɬɢɱɧɢ ɤɚɪɰɢɧɨɦ ɛɭɛɪɟɝɚ Ɉɜɚʁ ɨɛɥɢɤ ɬɭɦɨɪɚ ɱɢɧɢ 4% ɫɜɢɯ ɤɚɪɰɢɧɨɦɚ ɫɜɟɬɥɢɯ ʄɟɥɢʁɚ ɛɭɛɪɟɝɚ. Ƚɟɧɟɬɫɤɟ ɫɬɭɞɢʁɟ ɫɭ ɩɨɤɚɡɚɥɟ ʁɚɫɧɭ ɩɨɜɟɡɚɧɨɫɬ ɢɡɦɟђɭ ɦɭɥɬɢɥɨɤɭɥɚɪɧɨɝ ɰɢɫɬɢɱɧɨɝ ɄȻɢ ɫɄȻ. Ⱦɟɥɟɰɢʁɚ ɯɪɨɦɨɡɨɦɚ 3p ʁɟ ɧɚђɟɧɚ ɤɨɞ 74% ɨɜɢɯ ɬɭɦɨɪɚ, ɚ ɦɭɬɚɰɢʁɚ VHL ɝɟɧɚ ɤɨɞ 25%. Ʉɚɨ ɢ ɤɨɞ ɫɄȻ, ɬɭɦɨɪɫɤɟ ʄɟɥɢʁɟ ɭ ɜɟʄɢɧɢ ɫɥɭɱɚʁɟɜɚ ɩɨɤɚɡɭʁɭ ʁɚɤɭ ɩɨɡɢɬɢɜɧɨɫɬ ɧɚ PAX2 ɢ CA960. 1.4.5. Ɍɪɚɧɫɥɨɤɚɰɢɨɧɢ ɤɚɪɰɢɧɨɦɢ ɛɭɛɪɟɝɚ Ɍɪɚɧɫɥɨɤɚɰɢɨɧɢ ɤɚɪɰɢɧɨɦɢ ɛɭɛɪɟɝɚ ɫɟ ɭɝɥɚɜɧɨɦ ʁɚɜʂɚʁɭ ɤɨɞ ɞɟɰɟ ɢ ɦɥɚɞɢɯ ɨɞɪɚɫɥɢɯ ɨɫɨɛɚ, ɬɟ ɫɟ ɭ ɩɟɞɢʁɚɬɪɢʁɫɤɨʁ ɥɢɬɟɪɚɬɭɪɢ ɨɡɧɚɱɚɜɚʁɭ ɤɚɨ „ʁɭɜɟɧɢɥɧɢ ɤɚɪɰɢɧɨɦɢ”. ɍ ɧɚɫɬɚɧɚɤ ɬɪɚɧɫɥɨɤɚɰɢɨɧɢɯ ɤɚɪɰɢɧɨɦɚ ʁɟ ɭ ɜɟʄɢɧɢ ɫɥɭɱɚʁɟɜɚ (ɨɤɨ 90%) ɭɤʂɭɱɟɧ ɬɪɚɧɫɤɪɢɩɰɢɨɧɢ ɮɚɤɬɨɪ ȿ3 (TFE3) ɥɨɰɢɪɚɧ ɧɚ Xp11.2 ɥɨɤɭɫɭ61. 1.4.5.1. Ʉɚɪɰɢɧɨɦ ɛɭɛɪɟɝɚ ɭɞɪɭɠɟɧ ɫɚ Бp11.2 ɬɪɚɧɫɥɨɤɚɰɢʁɨɦ/TFE3 ɮɭɡɢʁɨɦ ɝɟɧɚ ɍȼɈȾ 8 Ɉɜɚʁ ɬɢɩ ɤɚɪɰɢɧɨɦɚ ɛɭɛɪɟɝɚ ɫɟ ɱɟɲʄɟ ʁɚɜʂɚ ɭ ɩɟɞɢʁɚɬɪɢʁɫɤɨʁ ɩɨɩɭɥɚɰɢʁɢ ɢ ɤɨɞ ɦɥɚɞɢɯ ɨɞɪɚɫɥɢɯ ɨɫɨɛɚ ɠɟɧɫɤɨɝ ɩɨɥɚ. ɑɢɧɢ ɨɤɨ 1% ɫɜɢɯ ɛɭɛɪɟɠɧɢɯ ɧɟɨɩɥɚɡɦɢ ɢ ɦɨɠɟ ɢɦɚɬɢ ɚɝɪɟɫɢɜɚɧ ɤɥɢɧɢɱɤɢ ɬɨɤ. ɉɪɟɞɫɬɚɜʂɚ ʁɟɞɚɧ ɨɞ ɫɤɨɪɢʁɟ ɢɧɞɟɧɬɢɮɢɤɨɜɚɧɢɯ ɩɨɞɬɢɩɨɜɚ ɄȻ, ɤɨʁɢ ʁɟ ɭɲɚɨ ɭ ɤɥɚɫɢɮɢɤɚɰɢʁɭ ɬɭɦɨɪɚ ɛɭɛɪɟɝɚ ɩɪɟɦɚ ɋɁɈ 2004. ɝɨɞɢɧɟ.Ɉɜɚʁ ɬɢɩ ɤɚɪɰɢɧɨɦɚ ɱɢɧɢ 1% ɞɨ 4% ɫɜɢɯ ɤɚɪɰɢɧɨɦɚ ɛɭɛɪɟɝɚ ɤɨɞ ɨɞɪɚɫɥɢɯ62. 1.4.5.2. Ʉɚɪɰɢɧɨɦ ɛɭɛɪɟɝɚ ɫɚ ɬɪɚɧɫɥɨɤɚɰɢʁɨɦ t(6;11)(p21:q12) Ɉɜɚʁ ɬɢɩ ɬɭɦɨɪɚ ɫɟ ɭɝɥɚɜɧɨɦ ʁɚɜʂɚ ɤɨɞ ɞɟɰɟ ɢ ɦɥɚɞɢɯ ɨɞɪɚɫɥɢɯ ɨɫɨɛɚ ɢ ɞɨ ɫɚɞɚ ʁɟ ɨɩɢɫɚɧɨ ɨɤɨ 30 ɝɟɧɟɬɫɤɢ ɞɨɤɚɡɚɧɢɯ ɫɥɭɱɚʁɟɜɚ ɨɜɨɝ ɬɢɩɚ ɤɚɪɰɢɧɨɦɚ ɛɭɛɪɟɝɚ ɭ ɫɜɟɬɭ. Ɉɜɚʁ ɬɢɩ ɬɭɦɨɪɚ ɤɚɪɚɤɬɟɪɢɲɟ t(6;11)(p21:q12), ɲɬɨ ɪɟɡɭɥɬɭʁɟ ɭ Alpha-TFEB ɮɭɡɢʁɢ ɝɟɧɚ63. 1.4.6. Ɇɭɰɢɧɨɡɧɢ ɬɭɛɭɥɚɪɧɢ ɢ ɜɪɟɬɟɧɚɫɬɢ ɤɚɪɰɢɧɨɦ ɛɭɛɪɟɝɚ Ɉɜɚʁ ɪɟɞɚɤ ɬɢɩ ɤɚɪɰɢɧɨɦɚ ɛɭɛɪɟɝɚ ʁɟ ɩɪɜɢ ɩɭɬ ɭɜɪɲɬɟɧ ɭ ɚɤɬɭɟɥɧɭ ɤɥɫɢɮɢɤɚɰɢʁɭ WHO. ȳɚɜʂɚ ɫɟ 3 ɞɨ 4 ɩɭɬɚ ɱɟɲʄɟ ɤɨɞ ɨɫɨɛɚ ɠɟɧɫɤɨɝ ɩɨɥɚ, ɧɚʁɱɟɲʄɟ ʁɟ ɚɫɢɦɩɬɨɦɚɬɫɤɢ, ɦɚɞɚ ɦɨɠɟ ɛɢɬɢ ɭɞɪɭɠɟɧ ɢ ɫɚ ɧɟɮɪɨɥɢɬɢʁɚɡɨɦ64. Ɉɜɢ ɬɭɦɨɪɢ ɢɦɚʁɭ ɧɚʁɱɟɲʄɟ ɢɧɞɨɥɟɧɬɚɧ ɤɥɢɧɢɱɤɢ ɬɨɤ ʁɟɪ ɫɭ ɧɢɫɤɨɝ ɫɬɟɩɟɧɚ ɦɚɥɢɝɧɢɬɟɬɚ (pT1, pT2) ɭ ɜɪɟɦɟ ɞɢʁɚɝɧɨɡɟ, ɚɥɢ ɫɭ ɧɟɞɚɜɧɨ ɨɩɢɫɚɧɢ ɢ ɫɥɭɱɚʁɟɜɢ ɫɚ ɚɝɪɟɫɢɜɧɢɦ ɬɨɤɨɦ65. 1.4.7. Ʉɚɪɰɢɧɨɦ Ȼɟɥɢɧɢʁɟɜɢɯ ɫɚɛɢɪɧɢɯ ɤɚɧɚɥɢʄɚ ɂɧɰɢɞɟɧɰɚ ɨɜɨɝ ɬɭɦɨɪɚ ɢɡɧɨɫɢ ɦɚʃɟ ɨɞ 1%, ɚɥɢ ʁɟ ʃɟɝɨɜɚ ɩɪɨɝɧɨɡɚ ɥɨɲɚ, ɫɚ ɫɦɪɬɧɢɦ ɢɫɯɨɞɨɦ ɤɨɞ 2/3 ɩɚɰɢʁɟɧɚɬɚ ɭɧɭɬɚɪ 2 ɝɨɞɢɧɟ ɨɞ ɞɢʁɚɝɧɨɫɬɢɤɨɜɚʃɚ ʁɟɪ ɫɟ ɧɚʁɱɟɲʄɟ ɢɫɩɨʂɚɜɚ ɭ Ɍ3 ɢ Ɍ4 ɫɬɚɞɢʁɭɦɭ. ɉɪɟɦɚ ɪɟɡɭɥɬɚɬɢɦɚ ɞɨɫɚɞɚɲʃɢɯ ɢɫɬɪɚɠɢɜɚʃɚ, ɧɟ ɩɨɫɬɨʁɢ ɫɩɟɰɢɮɢɱɧɚ ɝɟɧɟɬɫɤɚ ɚɛɧɨɪɦɚɥɧɨɫɬ ɡɚ ɨɜɚʁ ɬɢɩ ɬɭɦɨɪɚ, ɩɪɢ ɱɟɦɭ ɩɨɫɬɨʁɟ ɩɨɬɟɲɤɨʄɟ ɭ ʃɝɨɜɨʁ ɞɢɮɟɪɟɧɰɢʁɚɰɢʁɢ ɭ ɨɞɧɨɫɭ ɧɚ ɭɪɨɬɟɥɧɢ ɤɚɪɰɢɧɨɦ66. 1.4.8.Ɇɟɞɭɥɚɪɧɢ ɤɚɪɰɢɧɨɦ ɛɭɛɪɟɝɚ Ɉɜɚ ɬɢɩ ɤɚɪɰɢɧɨɦɚ ʁɟ ɩɪɜɢ ɩɭɬ ɨɩɢɫɚɧ ɨɞ ɫɬɪɚɧɟ Davis ɢ ɫɚɪ. 1995. ɝɨɞɢɧɟ67,68.ȳɚɜʂɚ ɫɟ ɫɤɨɪɨ ɢɫɤʂɭɱɢɜɨ ɭ ɞɟɱʁɨʁ ɩɨɩɭɥɚɰɢʁɢ ɢ ɤɨɞ ɦɥɚɞɢɯ ɨɞɪɚɫɥɢɯ ɨɫɨɛɚ ɫɚ ɫɪɩɚɫɬɨɦ ɚɧɟɦɢʁɨɦ. Ɉɜɢ ɬɭɦɨɪɢ ɱɟɫɬɨ ɩɨɤɚɡɭʁɭ ɪɚɛɞɨɢɞɧɟ ɰɢɬɨɥɨɲɤɟ ɤɚɪɚɤɬɟɪɢɫɬɢɤɟ ɡɛɨɝ ɱɟɝɚ ɫɭ ɚɝɪɟɫɢɜɧɨɝ ɢ ɜɟʄɢɧɨɦ ɥɟɬɚɥɧɨɝ ɬɨɤɚ. Ɉɛɨɥɟɥɢ ɨɞ ɨɜɨɝ ɩɨɞɬɢɩɚ ɄȻ ɩɨɤɚɡɭʁɭ ɩɨɜɟʄɚɧɭ ɟɤɫɩɪɟɫɢʁɭ HIF1α, ɦɚɞɚ ʁɨɲ ɧɢʁɟ ɭɬɜɪђɟɧɚ ʁɟɞɢɧɫɬɜɟɧɚ ɯɪɨɦɨɡɨɦɫɤɚ ɢɥɢ ɦɨɥɟɤɭɥɚɪɧɚ ɚɛɧɨɪɦɚɥɧɨɫɬ ɤɨɞ ɨɜɨɝ ɬɢɩɚ ɤɚɪɰɢɧɨɦɚ69. 1.4.9.Ʉɚɪɰɢɧɨɦ ɛɭɛɪɟɝɚ ɭɞɪɭɠɟɧ ɫɚ ɫɬɟɱɟɧɨɦ ɰɢɫɬɢɱɧɨɦ ɛɨɥɟɫɬɢ ɛɭɛɪɟɝɚ Ɉɜɚʁ ɬɢɩ ɬɭɦɨɪɚ ɫɟ ɢɫɤʂɭɱɢɜɨ ʁɚɜʂɚ ɤɨɞ ɩɚɰɢʁɟɧɚɬɚ ɫɚ ɫɬɟɱɟɧɨɦ ɰɢɫɬɢɱɧɨɦ ɛɨɥɟɫɬɢ ɛɭɛɪɟɝɚ (ɟɧɝɥ. ɫɤɪ. ACKD-Acquired Cystic Kidney Disease). ɋɬɟɱɟɧɚ ɰɢɫɬɢɱɧɚ ɛɨɥɟɫɬ ɍȼɈȾ 9 ɛɭɛɪɟɝɚ ɫɟ ʁɚɜʂɚ ɫɟ ɤɨɞ ɛɨɥɟɫɧɢɤɚ ɧɚ ɞɢʁɚɥɢɡɢ ɢ ɤɚɪɚɤɬɟɪɢɲɟ ɫɟ ɪɚɡɜɨʁɟɦ ɛɪɨʁɧɢɯ ɰɢɫɬɢ ɢɫɩɭʃɟɧɢɯ ɬɟɱɧɨɲʄɭ. ɉɪɟɜɚɥɟɧɰɚ ACKD ɢɡɧɨɫɢ 30% ɞɨ 90% ɢ ɪɚɫɬɟ ɫɚ ɞɭɠɢɧɨɦ ɞɢʁɚɥɢɡɧɨɝ ɫɬɚɠɚ, ɩɪɢ ɱɟɦɭ ʁɟ ɬɚɱɚɧ ɪɚɡɥɨɝ ɡɚ ɧɚɫɬɚɧɚɤ ɰɢɫɬɢ ɧɟɩɨɡɧɚɬ. Ɉɜɢ ɩɚɰɢʁɟɧɬɢ ɢɦɚʁɭ ɢ ɞɨ 100 ɩɭɬɚ ɜɟʄɢ ɪɢɡɢɤ ɡɚ ɪɚɡɜɨʁ ɄȻ ɭ ɨɞɧɨɫɭ ɧɚ ɨɩɲɬɭ ɩɨɩɭɥɚɰɢʁɭ. ACD-RCC (ɟɧɝɥ. ɫɤɪ. ɚcquТrОd cвstТc disease–associated renal cell carcinoma) ɱɢɧɢ 36% ɫɜɢɯ ɬɭɦɨɪɚ ɤɨɞ ɛɨɥɟɫɧɢɤɚ ɫɚ ɬɟɪɦɢɧɚɥɧɨɦ ɛɭɛɪɟɠɧɨɦ ɢɧɫɭɮɢɰɢʁɟɧɰɢʁɨɦ. Ɉɜɚʁ ɬɢɩ ɬɭɦɨɪɚ ɢɦɚ ɪɟɥɚɬɢɜɧɨ ɞɨɛɪɨ ɩɪɨɝɧɨɡɭ ʁɟɪ ɫɟ ɨɬɤɪɢɜɚ ɭ ɪɚɧɨɦ ɫɬɚɞɢʁɭɦɭ ɬɨɤɨɦ ɪɟɞɨɜɧɢɯ ɩɪɚʄɟʃɚ ɨɜɢɯ ɛɨɥɟɫɧɢɤɚ, ɚɥɢ ʁɟ ɚɝɪɟɫɢɜɧɢʁɟɝ ɬɨɤɚ ɭ ɨɞɧɨɫɭ ɧɚ ɨɫɬɚɥɟ ɬɢɩɨɜɟ ɤɚɪɰɢɧɨɦɚ ɛɭɛɪɟɝɚ ɤɨɞ ɨɜɢɯ ɛɨɥɟɫɧɢɤɚ, ɩɨɫɟɛɧɨ ɮɨɪɦɟ ɫɚ ɫɚɪɤɨɦɚɬɨɢɞɧɢɦ ɢ ɪɚɛɞɨɢɞɧɢɦ ɤɚɪɚɤɬɟɪɢɫɬɢɤɚɦɚ70,71. 1.4.10. ɋɜɟɬɥɨʄɟɥɢʁɫɤɢ ɩɚɩɢɥɚɪɧɢ ɤɚɪɰɢɧɨɦ ɛɭɛɪɟɝɚ Ɉɜɚʁ ɬɢɩ ɬɭɦɨɪɚ ɫɟ ʁɚɜʂɚ ɤɨɞ ɩɚɰɢʁɟɧɚɬɚ ɫɚ ɬɟɪɦɢɧɚɥɧɢɦ ɫɬɚɞɢʁɭɦɨɦ ɛɭɛɪɟɠɧɟ ɫɥɚɛɨɫɬɢ ɚɥɢ ɢ ɤɨɞ ɩɚɰɢʁɟɧɚɬɚ ɛɟɡ ɛɭɛɪɟɠɧɨɝ ɨɛɨʂɟʃɚ. ȵɟɝɨɜ ɤɥɢɧɢɱɤɢ ɬɨɤ ʁɟ ɝɟɧɟɪɚɥɧɨ ɢɧɞɨɥɟɧɬɚɧɬɚɧ, ɡɛɨɝ ɱɟɫɬɨ ɧɢɫɤɨɝ ɫɬɚɞɢʁɭɦɚ ɛɨɥɟɫɬɢ. Ɇɚɤɪɨɫɤɨɩɫɤɢ, ɨɜɢ ɬɭɦɨɪɢ ɫɭ ʁɚɫɧɨ ɨɝɪɚɧɢɱɟɧɢ ɤɚɩɫɭɥɨɦ ɢ ɰɢɫɬɢɱɧɨɝ ɨɛɥɢɤɚ72. 1.4.11. Ɍɭɛɭɥɨɰɢɫɬɢɱɧɢ ɤɚɪɰɢɧɨɦ ɛɭɛɪɟɝɚ ɍɤɭɩɧɨ ʁɟ ɞɨ ɫɚɞɚ ɭ ɥɢɬɟɪɚɬɭɪɢ ɨɛʁɚɜʂɟɧɨ ɦɚʃɟ ɨɞ 70 ɫɥɭɱɚʁɟɜɚ ɨɜɨɝ ɩɨɞɬɢɩɚ ɤɚɪɰɢɧɨɦɚ ɛɭɛɪɟɝɚ, ɤɨʁɢ ɫɟ ɫɟɞɚɦ ɩɭɬɚ ɱɟɲʄɟ ʁɚɜʂɚ ɤɨɞ ɨɫɨɛɚ ɦɭɲɤɨɝ ɩɨɥɚ. ɇɚʁɱɟɲʄɟ ʁɟ ɚɫɢɦɩɬɨɦɚɬɫɤɢ, ɪɚɞɢɨɥɨɲɤɢ ɫɟ ɧɚʁɱɟɲʄɟ ɦɚɧɢɮɟɫɬɭʁɟ ɤɚɨ ɤɨɦɩɥɟɤɫɧɚ ɰɢɫɬɚ ɢ ɯɢɫɬɨɥɨɲɤɢ ʁɟ ɭɝɥɚɜɧɨɦ ɧɢɫɤɨɝ ɫɬɟɩɟɧɚ ɦɚɥɢɝɧɢɬɟɬɚ73. 1.4.12. Ʉɚɪɰɢɧɨɦ ɛɭɛɪɟɝɚ ɭɞɪɭɠɟɧ ɫɚ ɧɟɭɪɨɛɥɚɫɬɨɦɨɦ Ɉɜɚʁ ɪɟɞɚɤ ɬɢɩ ɤɚɪɰɢɧɨɦɚ ɛɭɛɪɟɝɚ ʁɚɜʂɚ ɫɟ ɭ ɞɟɱʁɟɦ ɭɡɪɚɫɬɭ, ɤɨɞ ɨɫɨɛɚ ɥɟɱɟɧɢɯ ɨɞ ɧɟɭɪɨɛɥɚɫɬɨɦɚɉɪɜɢ ɩɭɬ ʁɟ ɭɜɪɲɬɟɧ ɭ ɤɥɚɫɢɮɢɤɚɰɢʁɭ ɤɚɪɰɢɧɨɦɚ ɛɭɛɪɟɝɚ ɋɁɈ 2004. ɝɨɞɢɧɟ74. 1.4.13. ɇɟɤɥɚɫɢɮɢɤɨɜɚɧɢ ɤɚɪɰɢɧɨɦ ɛɭɛɪɟɝɚ ɇɟɤɥɚɫɢɮɢɤɨɜɚɧɢ ɤɚɪɰɢɧɨɦ ɛɭɛɪɟɝɚ ʁɟ ɧɚɡɢɜ ɡɚ ɬɢɩ ɬɭɦɨɪɚ ɤɨʁɢ ɫɟ ɧɟ ɦɨɠɟ ɭɤɥɨɩɢɬɢ ɧɢ ɭ ʁɟɞɚɧ ɯɢɫɬɨɥɨɲɤɢ ɬɢɩ ɤɚɪɰɢɧɨɦɚ ɛɭɛɪɟɝɚ. Ɉɜɚʁ ɬɢɩ ɤɚɪɰɢɧɨɦɚ ɛɭɛɪɟɝɚ ʁɚɜʂɚ ɫɟ ɭ 4-6% ɫɜɢɯ ɬɭɦɨɪɚ ɛɭɛɪɟɝɚ. ɉɪɨɦɟɧɟ ɤɨʁɟ ɭɤɚɡɭʁɭ ɧɚ ɩɨɫɬɨʁɚʃɟ ɨɜɨɝ ɬɢɩɚ ɤɚɪɰɢɧɨɦɚ ɛɭɛɪɟɝɚ ɫɭ:  ɩɨɫɬɨʁɚʃɟ ɟɥɟɦɟɧɚɬɚ ɩɨɡɧɚɬɢɯ ɯɢɫɬɨɥɨɲɤɢɯ ɬɢɩɨɜɚ  ɱɢɫɬɚ ɫɚɪɤɨɦɚɬɨɢɞɧɚ ɦɨɪɮɨɥɨɝɢʁɚ ɛɟɡ ɩɪɟɩɨɡɧɚɬʃɢɜɢɯ ɟɩɢɬɟɥɧɢɯ ɤɚɪɚɤɬɟɪɢɫɬɢɤɚ  ɩɪɨɞɭɤɰɢʁɚ ɦɭɰɢɧɚ  ɪɟɬɤɚ ɤɨɦɛɢɧɚɰɢʁɚ ɟɩɢɬɟɥɧɢɯ ɢ ɫɬɪɨɦɚɥɧɢɯ ɟɥɟɦɟɧɚɬɚ  ɧɟɩɪɟɩɨɡɧɚɬʂɢɜɢ ɬɢɩɨɜɢ ʄɟɥɢʁɚ ɍȼɈȾ 10 Ɋɟɡɭɥɬɚɬɢ ɞɨɫɚɞɚɲʃɢɯ ɢɫɩɢɬɢɜɚʃɚ, ɤɨʁɢ ɫɭ ɥɢɦɢɬɢɪɚɧɢ ɦɚɥɢɦ ɛɪɨʁɟɦ ɫɬɭɞɢʁɚ ɢ ɢɫɩɢɬɚɧɢɤɚ, ɭɤɚɡɭʁɭ ɞɚ ɧɟɤɥɚɫɢɮɢɤɨɜɚɧɢ ɄȻ ɩɪɟɞɫɬɚɜʂɚ ɚɝɪɟɫɢɜɧɭ ɮɨɪɦɭ ɤɚɪɰɢɧɨɦɚ ɛɭɛɪɟɝɚ ɤɨʁɢ ɫɟ ɨɬɤɪɢɜɚ ɭ ɭɡɧɚɩɪɟɞɨɜɚɥɨɦ ɫɬɚɞɢʁɭɦɭ, ɤɚɨ ɢ ɞɚ ɧɢʁɟ ɛɢɥɨ ɡɧɚɱɚʁɧɟ ɪɚɡɥɢɤɟ ɭ ɩɪɟɠɢɜʂɚɜɚʃɭ ɭ ɨɞɧɨɫɭ ɧɚ ɨɛɨɥɟɥɟ ɨɞ ɫɄȻ75. 1.5.ɄɅɂɇɂɑɄȺ ɋɅɂɄȺ ɉɚɰɢʁɟɧɬɢ ɫɚ ɫɄȻ ɦɨɝɭ ɫɟ ɤɥɢɧɢɱɤɢ ɩɪɟɡɟɧɬɨɜɚɬɢ ɪɚɡɥɢɱɢɬɢɦ, ɱɟɫɬɨ ɧɟɫɩɟɰɢɮɢɱɧɢɦ ɫɢɦɩɬɨɦɢɦɚ, ɩɪɢ ɱɟɦɭ ɜɟʄɢɧɚ ɨɫɬɚʁɟ ɚɫɢɦɩɬɨɦɚɬɫɤɚ ɞɨ ɫɬɚɞɢʁɭɦɚ ɭɡɧɚɩɪɟɞɨɜɚɥɟ ɛɨɥɟɫɬɢ. ɋɚɦɨ 5-10% ɩɚɰɢʁɟɧɚɬɚ ɢɦɚ ɤɥɚɫɢɱɧɭ ȼɢɪɯɨɜʂɟɜɭ ɬɪɢʁɚɞɭ ɤɥɢɧɢɱɤɢɯ ɫɢɦɩɬɨɦɚ, ɤɨʁɭ ɱɢɧɟ: ɥɭɦɛɚɥɧɢ ɛɨɥ, ɦɚɤɪɨɫɤɨɩɫɤɚ ɯɟɦɚɬɭɪɢʁɚ ɢ ɩɚɥɩɚɛɢɥɧɚ ɬɭɦɨɪɫɤɚ ɦɚɫɚ76. Ʉɨɞ ɨɫɬɚɥɢɯ ɩɚɰɢʁɟɧɚɬɚ ɦɨɝɭ ɫɟ ʁɚɜɢɬɢ ɧɟɫɩɟɰɢɮɢɱɧɢ ɫɢɦɩɬɨɦɢ, ɤɚɨ ɲɬɨ ɫɭ: ɝɭɛɢɬɚɤ ɚɩɟɬɢɬɚ, ɭɦɨɪ, ɝɭɛɢɬɚɤ ɭ ɬɟɥɟɫɧɨʁ ɦɚɫɢ ɢ ɩɨɜɢɲɟɧɚ ɬɟɥɟɫɧɚ ɬɟɦɩɟɪɚɬɭɪɚ77.Ʉɚɪɰɢɧɨɦ ɛɭɛɪɟɝɚ ʁɟ ʁɟɞɚɧ ɨɞ ɦɚɥɢɝɧɢɬɟɬɚ ɤɨʁɢ ɞɚʁɟ ɧɚʁɢɡɪɚɠɟɧɢʁɢ ɩɚɪɚɧɟɨɩɥɚɫɬɢɱɧɢ ɫɢɧɞɪɨɦ (ɉɇɋ)78. ɍɱɟɫɬɚɥɨɫɬ ɉɇɋ ɭ ɨɜɨʁ ɝɪɭɩɢ ɩɚɰɢʁɟɧɚɬɚ ɢɡɧɨɫɢ 10% ɞɨ 40% ɢ ɩɪɢɫɭɬɚɧ ʁɟ ɢɥɢ ɭ ɜɪɟɦɟ ɞɢʁɚɝɧɨɡɟ ɢɥɢ ɬɨɤɨɦ ɛɨɥɟɫɬɢ79. Ⱦɟɮɢɧɢɲɟ ɫɟ ɤɚɨ ɩɨɫɬɨʁɚʃɟ ɫɢɫɬɟɦɫɤɢɯ ɫɢɦɩɬɨɦɚ ɤɨɞ ɨɛɨɥɟɥɢɯ ɩɚɰɢʁɟɧɚɬɚ, ɤɨʁɢ ɩɨɬɢɱɭ ɨɞ ɫɚɦɨɝ ɬɭɦɨɪɚ, ɚ ɧɢɫɭ ɩɨɫɥɟɞɢɰɚ ɦɟɬɚɫɬɚɬɫɤɢɯ ɩɪɨɦɟɧɚ, ɧɢɬɢ ɩɪɢɦɟʃɟɧɟ ɬɟɪɚɩɢʁɟ80. ȼɟʄɢɧɚ ɫɢɦɩɬɨɦɚ ʁɟ ɩɨɫɥɟɞɢɰɚ ɩɪɨɬɟɢɧɚ ɤɨʁɟ ɥɭɱɢ ɫɚɦ ɬɭɦɨɪ ɢɥɢ ɫɟɤɭɧɞɚɪɧɨ ɢɦɭɧɫɤɢ ɫɢɫɬɟɦ. ɂ ɩɨɪɟɞ ɬɨɝɚ, ɞɟɬɚʂɚɧ ɦɟɯɚɧɢɡɚɦ ɧɚɫɬɚɧɤɚ ɉɇɋ ʁɟ ɧɟɞɨɜɨʂɧɨ ɩɨɡɧɚɬ. ɋɦɚɬɪɚ ɫɟ ɞɚ ɭ ɨɫɧɨɜɢ ʃɟɝɨɜɨɝ ɧɚɫɬɚɧɤɚ ɫɬɨʁɢ ɩɨɜɟʄɚɧɨ ɥɭɱɟʃɟ ɰɢɬɨɤɢɧɚ, ɤɚɨ ɲɬɨ ʁɟ ɢɧɬɟɪɥɟɭɤɢɧ-6 (IL-6)81. ɂɧɬɟɪɥɟɭɤɢɧ-6 ʁɟ ɰɢɬɨɤɢɧ ɩɨɜɟɡɚɧ ɫɚ ɢɧɮɥɚɦɚɬɨɪɧɢɦ ɩɪɨɰɟɫɨɦ ɢ ɨɞɝɨɜɨɪɚɧ ʁɟ ɡɚ ɢɧɮɥɚɦɚɬɨɪɧɢ ɫɢɧɞɪɨɦ ɭ ɨɤɜɢɪɭ ɉɇɋ ɤɚɨ ɲɬɨ ɫɭ: ɩɨɜɢɲɟɧɚ ɬɟɦɩɟɪɚɬɭɪɚ, ɋɬɚɭɮɟɪ-ɨɜ ɫɢɧɞɪɨɦ, ɭɛɪɡɚɧɚ ɫɟɞɢɦɟɧɬɚɰɢʁɚ, ɚɧɟɦɢʁɚ ɢ ɬɪɨɦɛɨɰɢɬɨɡɚ82. ɉɨɫɬɨʁɢ ɜɢɲɟ ɨɞ 15 ɪɚɡɥɢɱɢɬɢɯ ɦɚɧɢɮɟɫɬɚɰɢʁɚ ɉɇɋ ɧɚɫɬɚɥɨɝ ɭ ɫɤɥɨɩɭɫɄȻ, ɤɨʁɢ ɫɟ ɦɨɝɭ ɩɨɞɟɥɢɬɢ ɭ ɞɜɟ ɨɫɧɨɜɧɟ ɝɪɭɩɟ: ɟɧɞɨɤɪɢɧɭ ɢ ɧɟɟɧɞɨɤɪɢɧɭ. ɍ ɟɧɞɨɤɪɢɧɭ ɝɪɭɩɭ ɫɩɚɞɚʁɭ: ɯɢɩɟɪɤɚɥɰɟɦɢʁɚ, ɯɢɩɟɪɬɟɧɡɢʁɚ, ɩɨɥɢɰɢɬɟɦɢʁɚ, ɧɟɦɟɬɚɫɬɚɬɫɤɚ ɯɟɩɚɬɢɱɧɚ ɞɢɫɮɭɧɤɰɢʁɚ (ɋɬɚɭɮɟɪ-ɨɜ ɫɢɧɞɪɨɦ), ɝɚɥɚɤɬɨɪɟʁɚ, Ʉɭɲɢɧɝ-ɨɜ ɫɢɧɞɪɨɦ ɢ ɩɨɪɟɦɟʄɚʁ ɭ ɦɟɬɚɛɨɥɢɡɦɭ ɝɥɭɤɨɡɟ. ɍ ɧɟɟɧɞɨɤɪɢɧɭ ɝɪɭɩɭ ɫɟ ɭɛɪɚʁɚʁɭ: ɚɦɢɥɨɢɞɨɡɚ, ɚɧɟɦɢʁɚ, ɧɟɭɪɨɦɢɨɩɚɬɢʁɚ, ɜɚɫɤɭɥɨɩɚɬɢʁɚ, ɧɟɮɪɨɩɚɬɢʁɚ, ɤɨɚɝɭɥɨɩɚɬɢʁɚ ɢ ɩɨɜɟʄɚʃɟ ɩɪɨɫɬɚɝɥɚɧɞɢɧɚ83. ȼɟʄɢɧɚ ɫɢɦɩɬɨɦɚ ɉɇɋ ʁɟ ɩɨɜɟɡɚɧɚ ɫɚ ɥɨɲɨɦ ɩɪɨɝɧɨɡɨɦ ɨɛɨɥɟɥɢɯ, ɩɪɢ ɱɟɦɭ ɫɭ ɫɚɦɨ ɧɟɤɢ ɨɞ ʃɢɯ ɩɨɜɟɡɚɧɢ ɫɚ ɫɬɚɞɢʁɭɦɨɦ ɢɥɢ ɝɪɚɞɭɫɨɦ ɬɭɦɨɪɚ. 1.5.1. ȿɧɞɨɤɪɢɧɟ ɦɚɧɢɮɟɫɬɚɰɢʁɟ ɩɚɪɚɧɟɨɩɥɚɫɬɢɱɧɨɝ ɫɢɧɞɪɨɦɚ ɏɢɩɟɪɤɚɥɰɟɦɢʁɚ ɏɢɩɟɪɤɚɥɰɟɦɢʁɚ ɩɪɟɞɫɬɚɜʂɚ ɧɚʁɱɟɲʄɢ ɡɧɚɤ ɉɇɋ ɢ ʁɚɜʂɚ ɫɟ ɤɨɞ 13% ɞɨ 20% ɩɚɰɢʁɟɧɚɬɚ ɫɚ ɄȻ84. Ɇɨɠɟ ɫɟ ɩɨɞɟɥɢɬɢ ɧɚ: ɦɟɬɚɫɬɚɬɫɤɭ ɢ ɧɟɦɟɬɚɫɬɚɬɫɤɭ ɯɢɩɟɪɤɚɥɰɟɦɢʁɭ. ɏɢɩɟɪɤɚɥɰɟɦɢʁɚ ɢɡɚɡɜɚɧɚ ɥɢɬɢɱɤɢɦ ɟɮɟɤɬɨɦ ɤɨɲɬɚɧɢɯ ɦɟɬɚɫɬɚɡɚ ɧɚɡɢɜɚ ɫɟ ɦɟɬɚɫɬɚɬɫɤɚ ɢ ɧɟ ɩɪɢɩɚɞɚ ɉɇɋ. ɇɟɦɟɬɚɫɬɚɬɫɤɚ ɯɢɩɟɪɤɚɥɰɟɦɢʁɚ ɢɫɤʂɭɱɭʁɟ ɯɢɩɟɪɤɚɥɰɟɦɢʁɭ ɢɡɚɡɜɚɧɭ ɍȼɈȾ 11 ɤɨɲɬɚɧɢɦ ɦɟɬɚɫɬɚɡɚɦɚ ɢ ɭɡɪɨɤɨɜɚɧɚ ʁɟ ɥɭɱɟʃɟɦ ɩɚɪɚɬɢɪɟɨɢɞɧɨɝ ɯɨɪɦɨɧɚ (PTH) ɢ ɩɚɪɚɬɢɪɟɨɢɞɧɨɦ ɯɨɪɦɨɧɭ ɫɥɢɱɧɨɝ ɩɟɩɬɢɞɚ (ɟɧɝɥ. ɫɤɪ. PTHrP-parathyroid hormone-related peptide) ɨɞ ɫɬɪɚɧɟ ɬɭɦɨɪɫɤɢɯ ʄɟɥɢʁɚ85. Ʉɥɢɧɢɱɤɢ ɫɟ ɦɨɠɟ ɦɚɧɢɮɟɫɬɨɜɚɬɢ ɪɚɡɥɢɱɢɬɢɦ ɫɢɦɩɬɨɦɢɦɚ ɤɚɨ ɲɬɨ ɫɭ: ɥɟɬɚɪɝɢʁɚ, ɭɦɨɪ, ɫɥɚɛɨɫɬ, ɦɭɱɧɢɧɚ, ɤɨɧɮɭɡɢʁɚ ɢ ɤɨɧɫɬɢɩɚɰɢʁɚ. Ɉɜɚʁ ɬɢɩ ɯɢɩɟɪɤɚɥɰɟɦɢʁɟ ɫɟ ɦɨɠɟ ɭɫɩɟɲɧɨ ɥɟɱɢɬɢ ɩɪɢɦɟɧɨɦ ɪɚɡɥɢɱɢɬɢɯ ɩɚɥɢʁɚɬɢɜɧɢɯ ɦɟɬɨɞɚ (ɬɟɱɧɨɫɬ, ɞɢɭɪɟɬɢɰɢ ɏɟɧɥɟɨɜɟ ɩɟɬʂɟ, ɛɢɮɨɫɮɨɧɚɬɢ) ɚɥɢ ɧɟɮɪɟɤɬɨɦɢʁɚ ɩɪɟɞɫɬɚɜʂɚ ɧɚʁɟɮɟɢɤɚɫɧɢʁɢ ɜɢɞ ɥɟɱɟʃɚ86. ɏɢɩɟɪɬɟɧɡɢʁɚ ɏɢɩɟɪɬɟɧɡɢʁɚ ɩɪɟɞɫɬɚɜʂɚ ɞɪɭɝɭ ɧɚʁɱɟɲʄɭ ɦɚɧɢɮɟɫɬɚɰɢʁɭ ɉɇɋ-ɚ, ɱɢʁɚ ɢɧɰɢɞɟɧɰɚ ɢɡɧɨɫɢ ɢ ɞɨ 40%. Ɍɢɩɢɱɧɨ ɫɟ ʁɚɜʂɚ ɤɨɞ ɫɄȻ ɧɢɫɤɨɝ ɫɬɟɩɟɧɚ ɦɚɥɢɝɧɢɬɟɬɚ. Ɇɨɝɭʄɢ ɦɟɯɚɧɢɡɦɢ ɪɚɡɜɨʁɚ ɯɢɩɟɪɬɟɧɡɢʁɟ ɤɨɞ ɨɜɢɯ ɩɚɰɢʁɟɧɚɬɚ ɫɭ: ɩɨɜɟʄɚɧɚ ɫɟɤɪɟɰɢʁɚ ɪɟɧɢɧɚ, ɭɪɟɬɟɪɚɥɧɚ ɢɥɢ ɩɚɪɟɧɯɢɦɫɤɚ ɤɨɦɩɪɟɫɢʁɚ, ɩɨɫɬɨʁɚʃɟ ɚɪɬɟɪɢɨɜɟɧɫɤɟ ɮɢɫɬɭɥɟ ɢ ɩɨɥɢɰɢɬɟɦɢʁɚ87. ɉɨɥɢɰɢɬɟɦɢʁɚ ɉɨɥɢɰɢɬɟɦɢʁɚ ʁɟ ɩɨɫɥɟɞɢɰɚ ɩɨɜɟʄɚɧɟ ɫɟɤɪɟɰɢʁɟ ɟɪɢɬɪɨɩɨɟɬɢɧɚ (ȿɉɈ) ɨɞ ɫɬɪɚɧɟ ɬɭɦɨɪɫɤɢɯ ʄɟɥɢʁɚ ɡɛɨɝ ɢɧɚɤɬɢɜɚɰɢʁɟ VHL ɝɟɧɚ ɢ ʁɚɜʂɚ ɫɟ ɤɨɞ 1% ɞɨ 5% ɩɚɰɢʁɟɧɚɬɚ88. ɉɪɨɞɭɤɰɢʁɚ ȿɉɈ ɤɨɞ ɨɜɢɯ ɩɚɰɢʁɟɧɚɬɚ ɨɞɜɢʁɚ ɫɟ ɭ ɧɚʁɜɟʄɟɦ ɩɪɨɰɟɧɬɭ ɟɤɬɨɩɢɱɧɨ, ɨɞ ɫɬɪɚɧɟ ɬɭɦɨɪɫɤɢɯ ʄɟɥɢʁɚ. ɉɨɤɚɡɚɧɨ ʁɟ ɞɚ ɩɚɰɢʁɟɧɬɢ ɫɚ ɩɨɡɢɬɢɜɧɨɦ ɟɤɫɩɪɟɫɢʁɨɦ ȿɉɈ ɭ ɬɭɦɨɪɫɤɢɦ ʄɟɥɢʁɚɦɚ ɢɦɚʁɭ ɞɜɚ ɩɭɬɚ ɜɟʄɢ ɦɨɪɬɚɥɢɬɟɬ ɭ ɨɞɧɨɫɭ ɧɚ ɩɚɰɢʁɟɧɬɟ ɛɟɡ ɟɤɫɩɪɟɫɢʁɟ ȿɉɈ89. Ɇɚɞɚ ɞɜɟ ɬɪɟʄɢɧɟ ɩɚɰɢʁɟɧɚɬɚ ɢɦɚʁɭ ɩɨɜɟʄɚɧɭ ɤɨɧɰɟɧɬɪɚɰɢʁɭ ȿɉɈ, ɨɤɨ 8% ɨɛɨɥɟɥɢɯ ɪɚɡɜɢʁɟ ɟɪɢɬɪɨɰɢɬɨɡɭ, ɲɬɨ ɛɢ ɦɨɝɥɨ ɛɢɬɢ ɩɨɫɥɟɞɢɰɚ ɥɭɱɟʃɚ ɧɟɚɤɬɢɜɧɟ ɮɨɪɦɟ ȿɉɈ ɨɞ ɫɬɪɚɧɟ ɬɭɦɨɪɫɤɢɯ ʄɟɥɢʁɚ90. ɇɟɦɟɬɚɫɬɚɬɫɤɚ ɞɢɫɮɭɧɤɰɢʁɚ ʁɟɬɪɟ ɋɬɚɭɮɟɪ ʁɟ 1961. ɝɨɞɢɧɟ ɨɩɢɫɚɨ ɩɨɫɬɨʁɚʃɟ ɞɢɫɮɭɧɤɰɢʁɟ ʁɟɬɪɟ ɤɨɞ ɩɚɰɢʁɟɧɬɚ ɫɚ ɞɢʁɚɝɧɨɡɨɦ ɫɄȻ, ɛɟɡ ɦɟɬɚɫɬɚɡɚ ɭ ʁɟɬɪɢ, ɬɟ ʁɟ ɩɨɫɬɨʁɚʃɟ ɨɜɟ ɦɚɧɢɮɟɫɬɚɰɢʁɟ ɉɇɋ ɞɨɛɢɥɨ ɧɚɡɢɜ ɋɬɚɭɮɟɪ-ɨɜ ɫɢɧɞɪɨɦ91. ȳɚɜʂɚ ɫɟ ɤɨɞ 3% ɞɨ 20% ɨɛɨɥɟɥɢɯ. Ɇɟɯɚɧɢɡɚɦ ɧɚɫɬɚɧɤɚ ɨɜɨɝ ɫɢɧɞɪɨɦɚ ʁɟ ɧɟɞɨɜɨʂɧɨ ɪɚɡʁɚɲʃɟɧ. ɋɦɚɬɪɚ ɫɟ ɞɚ ɬɭɦɨɪ ɫɟɤɪɟɬɭʁɟ ɯɟɩɚɬɨɬɨɤɫɢɧɟ ɢɥɢ ɥɢɡɨɡɨɦɚɥɧɟ ɟɧɡɢɦɟ ɤɨʁɢ ɚɤɬɢɜɢɪɚʁɭ ɯɟɩɚɬɢɱɧɟ ɤɚɬɟɩɫɢɧɟ ɢɥɢ ɮɨɫɮɚɬɚɡɟ, ɤɨʁɟ ɞɨɜɨɞɟ ɞɨ ɨɲɬɟʄɟʃɚ ɯɟɩɚɬɨɰɢɬɚ. ɉɪɟɦɚ ɞɪɭɝɨʁ ɬɟɨɪɢʁɢ ɬɭɦɨɪ ɫɟɤɪɟɬɭʁɟ ɯɟɩɚɬɨɬɨɤɫɢɧɟ ɤɨʁɢ ɞɨɜɨɞɟ ɞɨ ɨɲɬɟʄɟʃɚ ɯɟɩɚɬɨɰɢɬɚ ɩɪɟɤɨ ɚɤɬɢɜɚɰɢʁɟ ɢɦɭɧɫɤɨɝ ɫɢɫɬɟɦɚ ɢ ɩɪɨɞɭɤɰɢʁɟ ɚɧɬɢɬɟɥɚ ɧɚ ɚɧɬɢɝɟɧɟ ʁɟɬɪɟ92. Ʉɥɢɧɢɱɤɢ ɫɟ ɢɫɩɨʂɚɜɚ ɝɭɛɢɬɤɨɦ ɬɟɥɟɫɧɟ ɦɚɫɟ, ɩɨɜɢɲɟɧɨɦ ɬɟɥɟɫɧɨɦ ɬɟɦɩɟɪɚɬɭɪɨɦ ɢ ɭɦɨɪɨɦ ɢ ɩɪɟɞɫɬɚɜʂɚ ɥɨɲ ɩɪɨɝɧɨɫɬɢɱɤɢ ɡɧɚɤ. ɉɨɜɢɲɟɧɟ ɜɪɟɞɧɨɫɬɢ ɫɟɪɭɦɫɤɢɯ ɬɪɚɧɫɚɦɢɧɚɡɚ, ɤɚɨ ɥɚɛɨɪɚɬɨɪɢʁɫɤɢ ɩɚɪɚɦɟɬɪɢ ɯɟɩɚɬɢɱɧɟ ɞɢɫɮɭɧɤɰɢʁɟ, ɝɭɛɟ ɫɟ ɧɚɤɨɧ ɧɟɮɪɟɤɬɨɦɢʁɟ, ɚ ʃɢɯɨɜɚ ɩɨɧɨɜɧɚ ɩɨʁɚɜɚ ɦɨɠɟ ɭɤɚɡɢɜɚɬɢ ɧɚ ɥɨɤɚɥɧɭ ɪɟɤɭɪɟɧɰɢʁɭ ɛɨɥɟɫɬɢ ɢɥɢ ɩɨʁɚɜɭ ɭɞɚʂɟɧɢɯ ɦɟɬɚɫɬɚɡɚ. ɍȼɈȾ 12 Ʉɨɧɫɬɢɬɭɰɢɨɧɚɥɧɢ ɫɢɦɩɬɨɦɢ Ʉɨɞ ɩɪɢɛɥɢɠɧɨ ʁɟɞɧɟ ɬɪɟʄɢɧɟ ɨɛɨɥɟɥɢɯ, ɫɢɦɩɬɨɦɢ ɤɚɨ ɲɬɨ ɫɭ: ɩɨɜɢɲɟɧɚ ɬɟɥɟɫɧɚ ɬɟɦɩɟɪɚɬɭɪɚ, ɝɭɛɢɬɚɤ ɬɟɥɟɫɧɟ ɦɚɫɟ ɢ ɭɦɨɪ, ɩɪɟɞɫɬɚɜʂɚʁɭ ɩɪɜɟ ɫɢɦɩɬɨɦɟ ɫɄȻ93. ɇɚɜɟɞɟɧɢ ɤɨɧɫɬɢɬɭɰɢɨɧɚɥɧɢ ɫɢɦɩɬɨɦɢ ɫɭ ɩɨɫɥɟɞɢɰɚ ɩɨɜɟʄɚɧɨɝ ɥɭɱɟʃɚ ɨɞɪɟђɟɧɢɯ ɰɢɬɨɤɢɧɚ, ɤɚɨ ɲɬɨ ɫɭ TNF-α,IL-6 ɢ IL-182,94. ɍ ɫɬɭɞɢʁɢ Tsukamotɚ ɢ ɫɚɪ., ɤɨɞ 18 ɨɞ ɭɤɭɩɧɨ 71 ɩɚɰɢʁɟɧɬɚ ɞɨɤɚɡɚɧɚ ʁɟ ɩɨɜɢɲɟɧɚ ɤɨɧɰɟɧɬɪɚɰɢʁɚ IL-6, ɚ 78% ɨɧɢɯ ɫɚ ɩɨɜɢɲɟɧɢɦ ɧɢɜɨɨɦ IL-6 ɢɦɚɥɨ ʁɟ ɩɨɜɢɲɟɧɭ ɬɟɦɩɟɪɚɬɭɪɭ95. ɉɨɜɢɲɟɧɚ ɬɟɥɟɫɧɚ ɬɟɦɩɟɪɚɬɭɪɚ ɩɪɢɫɭɬɧɚ ʁɟ ɤɨɞ 20% ɩɚɰɢʁɟɧɚɬɚ. ɋɦɚɬɪɚ ɫɟ ɞɚ ɧɟɤɪɨɡɚ ɢ ɯɟɦɨɪɚɝɢʁɚ ɭ ɬɭɦɨɪɭ ɦɨɝɭ ɛɢɬɢ ɭɡɪɨɤ ɩɨɜɢɲɟɧɟ ɬɟɦɩɟɪɚɬɭɪɟ, ɩɪɢ ɱɟɦɭ ʁɟ ɜɢɲɚ ɬɟɦɩɟɪɚɬɭɪɚ ɩɨɫɥɟɞɢɰɚ ɩɨɜɟʄɚɧɟ ɚɩɫɨɪɩɰɢʁɟ ɧɟɤɪɨɬɢɱɧɢɯ ɫɭɩɫɬɚɧɰɢ. Ɉɛɢɱɧɨ ʁɟ ɢɧɬɟɪɦɢɬɟɧɬɧɚ ɢ ɩɪɚʄɟɧɚ ɧɨʄɧɢɦ ɡɧɨʁɟʃɟɦ, ɝɭɛɢɬɤɨɦ ɬɟɥɟɫɧɟ ɦɚɫɟ ɢ ɭɦɨɪɨɦ. ɇɚђɟɧɚ ʁɟ ɡɧɚɱɚʁɧɚ ɤɨɪɟɥɚɰɢʁɚ ɢɡɦɟђɭ ɩɨɜɢɲɟɧɟ ɬɟɦɩɟɪɚɬɭɪɟ ɢ ɭɡɧɚɩɪɟɞɨɜɚɥɨɝ ɫɬɚɞɢʁɭɦɚ ɛɨɥɟɫɬɢ96. Ɉɫɬɚɥɟ ɟɧɞɨɤɪɢɧɟ ɚɛɧɨɪɦɚɥɧɨɫɬɢ Ʉɨɞ ɩɚɰɢʁɟɧɚɬɚ ɨɛɨɥɟɥɢɯ ɨɞ ɫɄȻ ɦɨɝɭ ɫɟ ɢɫɩɨʂɢɬɢ ɪɚɡɥɢɱɢɬɟ ɟɧɞɨɤɪɢɧɟ ɚɛɧɨɪɦɚɥɧɨɫɬɢ ɤɨʁɟ ɫɟ ɦɚɧɢɮɟɫɬɭʁɭ ɩɨɜɢɲɟɧɢɦ ɜɪɟɞɧɨɫɬɢɦɚ ɫɟɪɭɦɫɤɢɯ ɤɨɧɰɟɧɬɪɚɰɢʁɚ ɨɞɪɟђɟɧɢɯ ɯɨɪɦɨɧɚ, ɤɚɨ ɲɬɨ ɫɭ: ɯɭɦɚɧɢ ɯɨɪɢɨɧɫɤɢ ɝɨɧɚɞɨɬɪɨɩɢɧ (HCG) ɢ ɚɞɪɟɧɨɤɨɪɬɢɤɨɬɪɨɩɧɢ ɯɨɪɦɨɧ (ACTH) ɢɥɢ ɤɚɨ ɤɥɢɧɢɱɤɢ ɫɢɧɞɪɨɦɢ ɤɚɨ ɲɬɨ ɫɭ ɝɚɥɚɤɬɨɪɟʁɚ, Ʉɭɲɢɧɝɨ-ɨɜ ɫɢɧɞɪɨɦ ɢ ɯɢɩɟɪ/ɯɢɩɨɝɥɢɤɟɦɢʁɚ97. ɉɨɜɢɲɟɧɚ ɜɪɟɞɧɨɫɬ β-HCG ɧɚђɟɧɚ ʁɟ ɤɨɞ ɩɪɢɛɥɢɠɧɨ 6% ɨɛɨɥɟɥɢɯ, ɩɪɢ ɱɟɦɭ ɧɢʁɟ ɧɚђɟɧɚ ɩɨɜɟɡɚɧɨɫɬ ɢɡɦɟђɭ ɤɨɧɰɟɧɬɪɚɰɢʁɟ β-HCG, ɫɬɚɞɢʁɭɦɚ ɛɨɥɟɫɬɢ ɢ ɩɪɟɠɢɜʂɚɜɚʃɚ98. ɉɨɪɟɦɟʄɚʁ ɭ ɦɟɬɚɛɨɥɢɡɦɭ ɝɥɭɤɨɡɟ ʁɟ ɨɩɢɫɚɧɚ ɤɨɞ ɨɛɨɥɟɥɢɯ ɨɞ ɄȻ, ɚ ɯɨɪɦɨɧɢ ɤɚɨ ɲɬɨ ɫɭ ɝɥɭɤɚɝɨɧ ɢ ɢɧɫɭɥɢɧ ɢɡɨɥɨɜɚɧɢ ɫɭ ɢɡ ɬɭɦɨɪɫɤɨɝ ɬɤɢɜɚ ɨɛɨɥɟɥɢɯ ɢ ɬɨ ɭ ɡɧɚɱɚʁɧɨ ɜɢɲɨʁ ɤɨɧɰɟɧɬɪɚɰɢʁɢ ɭ ɩɨɪɟђɟʃɭ ɫɚ ɤɨɧɬɪɨɥɚɦɚ99. Ƚɪɭɩɚ ɧɚɭɱɧɢɤɚ ʁɟ 1961. ɝɨɞɢɧɟ ɩɪɜɢ ɩɭɬ ɨɩɢɫɚɥɚ ɩɨɜɟɡɚɧɨɫɬ ɢɡɦɟђɭ ɄȻ ɢ Ʉɭɲɢɧɝɨɜ-ɨɝ ɫɢɧɞɪɨɦɚ100. Ɉɜɚ ɦɚɧɢɮɟɫɬɚɰɢʁɚ ɄȻ ɧɚɫɬɚʁɟ ɫɟɤɭɧɞɚɪɧɨ ɡɛɨɝ ɩɪɟɬɜɚɪɚʃɚ ɩɪɨ- ɨɩɢɨɦɟɥɚɧɨɤɨɪɬɢɧɚ ɭ ACTH ɨɞ ɫɬɪɚɧɟ ɬɭɦɨɪɚ, ɫɚ ɩɨɫɥɟɞɢɱɧɨɦ ɩɨɜɟʄɚɧɨɦ ɫɟɤɪɟɰɢʁɨɦ ɤɨɪɬɢɡɨɥɚ ɢ ɞɢɮɭɡɧɨɦ ɯɢɩɟɪɩɥɚɡɢʁɨɦ ɧɚɞɛɭɛɪɟɠɧɢɯ ɠɥɟɡɞɚ. Ɇɚɧɢɮɟɫɬɚɰɢʁɟ ɨɜɨɝ ɫɢɧɞɪɨɦɚ ɫɟ ɩɨɜɥɚɱɟ ɧɚɤɨɧ ɧɟɮɪɟɤɬɨɦɢʁɟ ɢ ɩɚɪɰɢʁɚɥɧɟ ɚɞɪɟɧɚɥɟɤɬɨɦɢʁɟ, ɚ ɩɨɧɨɜɧɢ ɩɨɪɚɫɬ ACTH ɦɨɠɟ ɭɤɚɡɢɜɚɬɢ ɧɚ ɩɪɨɝɪɟɫɢʁɭ ɛɨɥɟɫɬɢ101. Ƚɚɥɚɤɬɨɪɟɚ ɢ ɩɨɜɢɲɟɧɟ ɜɪɟɞɧɨɫɬɢ ɫɟɪɭɦɫɤɨɝ ɩɪɨɥɚɤɬɢɧɚ ɨɩɢɫɚɧɢ ɫɭ ɤɨɞ ɞɜɚ ɩɚɰɢʁɟɧɬɚ ɨɛɨɥɟɥɚ ɨɞ ɄȻ. ɂɦɭɧɨɥɨɲɤɢɦ ɢɫɩɢɬɢɜɚʃɢɦɚ ɧɚ ɬɭɦɨɪɫɤɢɦ ʄɟɥɢʁɚɦɚ ɢɧɞɟɧɬɢɮɢɤɨɜɚɧɚ ʁɟ ɫɭɩɫɬɚɧɰɚ ɤɨʁɚ ɩɨɤɚɡɭʁɟ ɭɤɪɲɬɟɧɭ ɪɟɚɤɰɢʁɭ ɫɚ ɚɧɬɢɩɪɨɥɚɤɬɢɧɫɤɢɦ ɚɧɬɢɬɟɥɢɦɚ102. 1.5.2. ɇɟɟɧɞɨɤɪɢɧɟ ɦɚɧɢɮɟɫɬɚɰɢʁɟ ɩɚɪɚɧɟɨɩɥɚɫɬɢɱɧɨɝ ɫɢɧɞɪɨɦɚ ɇɟɤɟ ɧɟɟɧɞɨɤɪɢɧɟ ɦɚɧɢɮɟɫɬɚɰɢʁɟ ɉɇɋ ɤɚɨ ɲɬɨ ɫɭ ɚɦɢɥɨɢɞɨɡɚ, ɧɟɭɪɨɦɢɨɩɚɬɢʁɚ, ɤɨɚɝɭɥɨɩɚɬɢʁɚ, ɜɚɫɤɭɥɨɩɚɬɢʁɚ ɢɥɢ ɧɟɮɪɨɩɚɬɢʁɚ ɤɨʁɚ ʁɟ ɢɡɚɡɜɚɧɚ ɬɚɥɨɠɟʃɟɦ ɥɚɤɢɯ ɥɚɧɚɰɚ, ʁɚɜʂɚʁɭ ɫɟ ɪɟɬɤɨ ɤɨɞ ɨɛɨɥɟɥɢɯ ɨɞ ɫɄȻ. ɇɟɭɪɨɦɢɨɩɚɬɢʁɚ ʁɟ ɨɩɢɫɚɧɚ ɤɨɞ ɧɟɦɟɬɚɫɬɚɬɫɤɢɯ ɍȼɈȾ 13 ɬɭɦɨɪɚ. Ʉɥɢɧɢɱɤɢ ɫɟ ɦɨɠɟ ɦɚɧɢɮɟɫɬɨɜɚɬɢ ɧɟɫɩɟɰɢɮɢɱɧɢɦ ɦɢɚɥɝɢʁɚɦɚ ɞɨ ɛɢɥɚɬɟɪɚɥɧɟ ɩɚɪɚɥɢɡɟ ɮɪɟɧɢɱɤɨɝ ɧɟɪɜɚ, ɚ ɨɩɢɫɚɧ ʁɟ ɢ ɫɥɭɱɚʁ ɪɚɡɜɨʁɚ ɚɦɢɨɬɪɨɮɢɱɤɟ ɥɚɬɟɪɚɥɧɟ ɫɤɥɟɪɨɡɟ103. Ⱥɦɢɥɨɢɞɨɡɚ ɫɟ ʁɚʂɚ ɤɨɞ 3% ɞɨ 8% ɨɛɨɥɟɥɢɯ. ɋɦɚɬɪɚ ɫɟ ɞɚ ʁɟ ɩɨɫɥɟɞɢɰɚ ɩɪɨɞɭɠɟɧɟ ɫɬɢɦɭɥɚɰɢʁɟ ɢɦɭɧɫɤɨɝ ɫɢɫɬɟɦɚ ɢɡɚɡɜɚɧɟ ɪɚɫɬɨɦ ɬɭɦɨɪɚ ɢɥɢ ɬɭɦɨɪɫɤɨɦ ɧɟɤɪɨɡɨɦ. Ɇɚɧɢɮɟɫɬɭʁɟ ɫɟ ɧɟɫɩɟɰɢɮɢɱɧɢɦ ɫɢɦɩɬɨɦɢɦɚ ɤɚɨ ɲɬɨ ɫɭ ɫɥɚɛɨɫɬ, ɝɭɛɢɬɚɤ ɬɟɥɟɫɧɟ ɦɚɫɟ ɢ ɩɨʁɚɜɚ ɫɢɧɤɨɩɟ, ɚ ɫɩɟɰɢɮɢɱɧɢ ɡɧɚɰɢ ɡɚɜɢɫɟ ɨɞ ɡɚɯɜɚɬɚʃɚ ɨɞɪɟђɟɧɢɯ ɨɪɝɚɧɚ, ɤɚɨ ɲɬɨ ɫɭ ɫɪɰɟ, ɛɭɛɪɟɝ, ɝɚɫɬɪɨɢɧɬɟɫɬɢɧɚɥɧɢ ɬɪɚɤɬ104. Ⱥɧɟɦɢʁɚ ɫɟ ɱɟɲʄɟ ʁɚɜʂɚ ɤɨɞ ɨɜɢɯ ɩɚɰɢʁɟɧɚɬɚ ɢ ɦɨɠɟ ɫɟ ɢɫɩɨʂɢɬɢ ɧɟɤɨɥɢɤɨ ɦɟɫɟɰɢ ɩɪɟ ɞɢʁɚɝɧɨɡɟ ɫɄȻ. ɍɱɟɫɬɚɥɨɫɬ ɩɨʁɚɜɟ ɚɧɟɦɢʁɟ ɢɡɧɨɫɢ ɨɞ 29% ɩɚ ɞɨ 88% ɤɨɞ ɭɡɧɚɩɪɟɞɨɜɚɥɨɝ ɫɬɚɞɢʁɭɦɚ ɛɨɥɟɫɬɢ. ɑɟɫɬɨ ʁɟ ɞɢɫɩɪɨɩɨɪɰɢɨɧɚɥɧɚ ɭ ɨɞɧɨɫɭ ɧɚ ɫɬɚɞɢʁɭɦ ɛɨɥɟɫɬɢ, ɧɨɪɦɨɰɢɬɧɚ ɢɥɢ ɦɢɤɪɨɰɢɬɧɚ, ɱɟɫɬɨ ɩɨɜɟɡɚɧɚ ɫɚ ɫɧɢɠɟɧɨɦ ɫɟɪɭɦɫɤɨɦ ɤɨɧɰɟɧɬɪɚɰɢʁɨɦ ɝɜɨɠђɚ, ɢɧɮɥɚɦɚɰɢʁɨɦ, ɬɭɦɨɪ-ɢɧɞɭɤɨɜɚɧɨɦ ɟɪɢɬɪɨɩɨɟɬɢɧɫɤɨɦ ɢɧɚɤɬɢɜɧɨɲʄɭ ɢ ɫɦɚʃɟɧɢɦ ɨɞɝɨɜɨɪɨɦ ɧɚ ɟɪɢɬɪɨɩɨɟɬɢɧ. Ɉɡɧɚɱɚɜɚ ɫɟ ɤɚɨ ɚɧɟɦɢʁɚ ɯɪɨɧɢɱɧɟ ɛɨɥɟɫɬɢ. Ɉɫɬɚɥɢ ɫɢɦɩɬɨɦɢ ɢ ɡɧɚɰɢ ɩɨɫɥɟɞɢɰɚ ɫɭ ɢɧɜɚɡɢʁɟ ɫɭɫɟɞɧɢɯ ɫɬɪɭɤɬɭɪɚ ɢɥɢ ɩɨɫɬɨʁɚʃɚ ɭɞɚʂɟɧɢɯ ɦɟɬɚɫɬɚɡɚ. ɏɟɦɚɬɭɪɢʁɚ ɫɟ ʁɚɜʂɚ ɭ ɫɥɭɱɚʁɟɜɢɦɚ ɬɭɦɨɪɫɤɟ ɢɧɜɚɡɢʁɟ ɫɚɛɢɪɧɨɝ ɫɢɫɬɟɦɚ ɛɭɛɪɟɝɚ. Ɋɚɡɜɨʁ ɜɚɪɢɤɨɰɟɥɟ ɤɨɞ ɩɚɰɢʁɟɧɚɬɚ ɦɭɲɤɨɝ ɩɨɥɚ, ɱɟɲʄɟ ɥɟɜɨɫɬɪɚɧɨ, ɩɨɫɥɟɞɢɰɚ ʁɟ ɩɪɢɫɭɫɬɜɚ ɬɭɦɨɪɫɤɨɝ ɬɪɨɦɛɚ ɭ ɥɟɜɨʁ ɪɟɧɚɥɧɨʁ ɜɟɧɢ ɢɥɢ ɞɨʃɨʁ ɲɭɩʂɨʁ ɜɟɧɢ ɢɥɢ ʃɢɯɨɜɟ ɫɩɨʂɧɟ ɤɨɦɩɪɟɫɢʁɟ ɨɞ ɫɬɪɚɧɟ ɬɭɦɨɪɚ, ɫɚ ɩɨɫɥɟɞɢɱɧɢɦ ɩɨɪɟɦɟʄɚʁɟɦ ɜɪɚʄɚʃɚ ɤɪɜɢ ɢɡ ɝɨɧɚɞɚɥɧɢɯ ɜɟɧɚ. Ɂɚɯɜɚɬɚʃɟ ɞɨʃɟ ɲɭɩʂɟ ɜɟɧɟ ɦɨɠɟ ɭɡɪɨɤɨɜɚɬɢ ɪɚɡɜɨʁ ɪɚɡɥɢɱɢɬɢɯ ɤɥɢɧɢɱɤɢɯ ɦɚɧɢɮɟɫɬɚɰɢʁɚɤɚɨɲɬɨɫɭ: ɨɬɨɤ ɞɨʃɢɯ ɟɤɫɬɪɟɦɢɬɟɬɚ, ɚɫɰɢɬɟɫ, ʁɟɬɪɟɧɚ ɞɢɫɮɭɧɤɰɢʁɚ ɢ ɩɥɭʄɧɚ ɬɪɨɦɛɨɟɦɛɨɥɢʁɚ83. ɉɨɡɧɚɬɨ ʁɟ ɞɚ ɩɨɫɬɨʁɢ ɭɫɤɚ ɩɨɜɟɡɚɧɨɫɬ ɢɡɦɟђɭ ɢɧɮɥɚɦɚɰɢʁɟ ɢ ɤɚɪɰɢɧɨɦɚ. ɂɧɞɭɤɰɢʁɚ ɩɟɪɢɬɭɦɨɪɫɤɟ ɢɧɮɥɚɦɚɰɢʁɟ ɪɟɡɭɥɬɭʁɟ ɭ ɩɨɜɟʄɚɧɨʁ ɫɢɧɬɟɡɢ ɪɟɚɤɬɚɧɬɚ ɚɤɭɬɧɟ ɮɚɡɟ ɭɩɚɥɟ, C ɪɟɚɤɬɢɜɧɨɝ ɩɪɨɬɟɢɧɚ (CRP) ɨɞ ɫɬɪɚɧɟ ɯɟɩɚɬɨɰɢɬɚ.ɋɢɫɬɟɦɫɤɢ ɢɦɭɧɢ ɨɞɝɨɜɨɪ ɞɨɦɚʄɢɧɚ ɧɚ ɬɭɦɨɪ, ɥɨɤɚɥɧɚ ɬɤɢɜɧɚ ɢɧɮɥɚɦɚɰɢʁɚ ɢɥɢ ɩɪɨɞɭɤɰɢʁɚ ɩɪɨɢɧɮɥɚɦɚɬɨɪɧɢɯ ɩɪɨɬɟɢɧɚ ɨɞ ɫɬɪɚɧɟ ɬɭɦɨɪɫɤɢɯ ʄɟɥɢʁɚ ɫɭ ɧɟɤɢ ɨɞ ɦɨɝɭʄɢɯ ɨɛʁɚɲʃɟʃɚ ɡɚ ɜɢɫɨɤɭ ɜɪɟɞɧɨɫɬ CRP-ɚ ɤɨɞ ɩɚɰɢʁɟɧɚɬɚ ɫɚ ɜɢɲɢɦ ɫɬɚɞɢʁɭɦɨɦ ɫɄȻ105. ȼɟɥɢɤɢ ɛɪɨʁ ɫɬɭɞɢʁɚ ʁɟ ɩɨɬɜɪɞɢɨ ɧɟɡɚɜɢɫɧɢ ɩɪɨɝɧɨɫɬɢɱɤɢ ɡɧɚɱɚʁ ɜɪɟɞɧɨɫɬɢ CRP-ɚ ɩɪɟ ɯɢɪɭɪɲɤɨɝ ɥɟɱɟʃɚ, ɤɚɨ ɢ ɨɩɫɟɝ ɤɨɧɰɟɧɬɪɚɰɢʁɚ ɨɞ 0,4 ɞɨ 2,3 mg/dl, ɚɥɢ ɧɢʁɟɞɧɚ ɫɬɭɞɢʁɚ ɧɢʁɟ ɨɞɪɟɞɢɥɚ ɩɨɬɟɧɰɢʁɚɥɧɨ ɧɚʁɛɨʂɢ ɩɪɚɝ ɜɪɟɞɧɨɫɬɢ ɨɜɨɝ ɦɚɪɤɟɪɚ. Ɍɪɨɦɛɨɰɢɬɨɡɚ ɫɟ ɪɟɬɤɨ ʁɚɜʂɚ ɢ ɩɪɟɞɫɬɚɜʂɚ ɥɨɲ ɩɪɨɝɧɨɫɬɢɱɤɢ ɡɧɚɤ. ɋɦɚɬɪɚ ɫɟ ɞɚ ʁɟ ɩɨɫɥɟɞɢɰɚ ɩɨɜɟʄɚɧɟ ɬɭɦɨɪɫɤɟ ɩɪɨɞɭɤɰɢʁɟ IL-6106,107. ɋɢɧɞɪɨɦ ɧɚɥɢɤ ɩɨɥɢɦɢʁɚɥɝɢʁɢ ɪɟɭɦɚɬɢɰɢ ɦɨɠɟ ɫɟ ʁɚɜɢɬɢ ɤɨɞ ɨɛɨɥɟɥɢɯ ɨɞ ɫɄȻ. Ʉɥɢɧɢɱɤɢ ɫɟ ɢɫɩɨʂɚɜɚ ʁɭɬɚɪʃɨɦ ɭɤɨɱɟɧɨɲʄɭ ɢ ɛɨɥɨɦ ɭ ɪɚɦɟɧɢɦ ɡɝɥɨɛɨɜɢɦɚ, ɤɭɤɨɜɢɦɚ, ɜɪɚɬɧɨʁ ɤɢɱɦɢ ɢ ɦɢɲɢʄɧɨɦ ɫɥɚɛɨɲʄɭ. Ɂɚ ɪɚɡɥɢɤɭ ɨɞ ɢɞɢɨɩɚɬɫɤɟ ɮɨɪɦɟ ɛɨɥɟɫɬɢ, ɧɟ ɞɨɥɚɡɢ ɞɨ ɩɨɛɨʂɲɚʃɚ ɫɢɦɩɬɨɦɚ ɧɚ ɩɪɢɦɟɧɭ ɤɨɪɬɢɤɨɫɬɟɪɨɢɞɧɟ ɬɟɪɚɩɢʁɟ ɚɥɢ ɫɟ ɨɧɢ ɱɟɫɬɨ ɝɭɛɟ ɧɚɤɨɧ ɧɟɮɪɟɤɬɨɦɢʁɟ108. ɍȼɈȾ 14 1.6.ȾɂȳȺȽɇɈɁȺ ɇɚʁɜɟʄɢ ɛɪɨʁ ɬɭɦɨɪɚ ɛɭɛɪɟɝɚ ɨɬɤɪɢɜɚ ɫɟ ɬɨɤɨɦ ɭɥɬɪɚɫɨɧɨɝɪɚɮɢʁɟ (ɍɋ) ɢɥɢ ɤɨɦɩʁɭɬɟɪɢɡɨɜɚɧɟ ɬɨɦɨɝɪɚɮɢʁɟ (ɄɌ) ɚɛɞɨɦɟɧɚ ɢɡ ɞɪɭɝɢɯ ɦɟɞɢɰɢɧɫɤɢɯ ɪɚɡɥɨɝɚ. Ɍɭɦɨɪɫɤɚ ɩɪɨɦɟɧɚ ɧɚ ɛɭɛɪɟɝɭ ɫɟ ɨɬɤɪɢʁɟ ɬɨɤɨɦ 13 ɞɨ 27% ɪɚɞɢɨɥɨɲɤɢɯ ɩɪɟɝɥɟɞɚ ɚɛɞɨɦɟɧɚ109. ȼɟʄɢɧɚ ɨɜɢɯ ɩɪɨɦɟɧɚ ɫɭ ɦɚɥɟ, ɨɛɢɱɧɟ ɰɢɫɬɟ ɤɨʁɟ ɧɟ ɩɨɤɚɡɭʁɭ ɩɨʁɚɱɚʃɟ ɧɚɤɨɧ ɩɪɢɦɟɧɟ ɤɨɧɬɪɚɫɬɧɨɝ ɫɪɟɞɫɬɜɚ, ɞɨɤ ɫɟ ɭ ɦɚʃɟɦ ɛɪɨʁɭ ɫɥɭɱɚʁɟɜɚ ɪɚɞɢ ɨ ɩɨɫɬɨʁɚʃɭ ɫɨɥɢɞɧɢɯ ɢɥɢ ɤɨɦɩɥɟɤɫɧɢɯ ɰɢɫɬɢɱɧɢɯ ɩɪɨɦɟɧɚ. ɉɨɜɟʄɚʃɟ ɞɟɧɡɢɬɟɬɚ ɡɚ ɜɢɲɟ ɨɞ 15 HU (HU-ɟɧɝɥ. ɫɤɪ. Hounsfield units) ɧɚɤɨɧ ɩɪɢɦɟɧɟ ɤɨɧɬɪɚɫɬɚ ɭɤɚɡɭʁɟ ɧɚ ɩɨɫɬɨʁɚʃɟ ɫɨɥɢɞɧɟ ɬɭɦɨɪɫɤɟ ɩɪɨɦɟɧɟ110. Ʉɨɦɩʁɭɬɟɪɢɡɨɜɚɧɨɦ ɬɨɦɨɝɪɚɮɢʁɨɦ ɚɛɞɨɦɟɧɚ ɞɨɛɢʁɚʁɭ ɫɟ ɢɧɮɨɪɦɚɰɢʁɟɨ: ɮɭɧɤɰɢʁɢ ɢ ɦɨɪɮɨɥɨɝɢʁɢ ɤɨɧɬɪɚɥɚɬɟɪɚɥɧɨɝ ɛɭɛɪɟɝɚ, ɟɤɫɬɪɚɪɟɧɚɥɧɨɦ ɲɢɪɟʃɭ ɩɪɢɦɚɪɧɨɝ ɬɭɦɨɪɚ, ɭɜɟʄɚʃɭ ɥɨɤɨɪɟɝɢɨɧɚɥɧɢɯ ɥɢɦɮɧɢɯ ɠɥɟɡɞɚ, ɡɚɯɜɚɬɚʃɭ ɜɟɧɫɤɢɯ ɤɪɜɧɢɯ ɫɭɞɨɜɚ ɢ ɫɬɚʃɭ ɧɚɞɛɭɛɪɟɠɧɢɯ ɠɥɟɡɞɚ ɢ ʁɟɬɪɟ111. ɍɤɨɥɢɤɨ ɫɭ ɩɚɰɢʁɟɧɬɢ ɚɥɟɪɝɢɱɧɢ ɧɚ ɤɨɧɬɪɚɫɬɧɨ ɫɪɟɞɫɬɜɨ, ɢɦɚʁɭ ɛɭɛɪɟɠɧɭ ɫɥɚɛɨɫɬ ɢɥɢ ɫɟ ɪɚɞɢ ɨ ɬɪɭɞɧɢɰɚɦɚ, ɢɧɞɢɤɨɜɚɧ ʁɟ ɩɪɟɝɥɟɞ ɚɛɞɨɦɟɧɚ ɦɚɝɧɟɬɧɨɦ ɪɟɡɨɧɚɧɰɨɦ (ɆɊ)112. Ɉɜɢɦ ɩɪɟɝɥɟɞɨɦ ɫɟ ɦɨɝɭ ɞɨɛɢɬɢ ɞɨɞɚɬɧɟ ɢɧɮɨɪɦɚɰɢʁɟ ɨ ɩɪɢɪɨɞɢ ɫɨɥɢɞɧɢɯ ɧɨɞɭɥɚɪɧɢɯ ɩɪɨɦɟɧɚ ɭ ɤɨɦɩɥɟɤɫɧɢɦ ɰɢɫɬɚɦɚ,ɥɨɤɚɥɧɨ ɭɡɧɚɩɪɟɞɨɜɚɥɨʁ ɛɨɥɟɫɬɢ ɢ ɡɚɯɜɚɬɚʃɭ ɜɟɧɫɤɢɯ ɤɪɜɧɢɯ ɫɭɞɨɜɚ, ɲɢɪɟʃɟ ɬɭɦɨɪɚ ɭ ɞɨʃɭ ɲɭɩʂɭ ɜɟɧɭ ɢ ɫɬɜɚɪɚʃɟ ɦɚɥɢɝɧɨɝ ɬɪɨɦɛɚ113,114. ɄɌ ɩɪɟɝɥɟɞ ɝɪɭɞɧɨɝ ɤɨɲɚ ɩɪɟɞɫɬɚɜʂɚ ɧɚʁɩɪɟɰɢɡɧɢʁɢ ɦɟɬɨɞ ɡɚ ɭɬɜɪђɢɜɚʃɟ ɫɬɚɞɢʁɭɦɚ ɛɨɥɟɫɬɢ ɢ ɩɪɢɫɭɫɬɜɨ ɦɟɬɚɫɬɚɬɫɤɢɯ ɩɪɨɦɟɧɚ ɭ ɩɥɭʄɢɦɚ115. ɋɰɢɧɬɢɝɪɚɮɢʁɭ ɫɤɟɥɟɬɚ, ɤɚɨ ɢ ɄɌ ɢɥɢ ɆɊ ɩɪɟɝɥɟɞ ɝɥɚɜɟ, ɧɟ ɬɪɟɛɚ ɪɚɞɢɬɢ ɭɤɨɥɢɤɨ ɧɟ ɩɨɫɬɨʁɟ ɫɩɟɰɢɮɢɱɧɢ ɤɥɢɧɢɱɤɢ ɢɥɢ ɥɚɛɨɪɚɬɨɪɢʁɫɤɢ ɡɧɚɰɢ ɡɚ ʃɢɯɨɜɨ ɩɨɫɬɨʁɚʃɟ116. ɉɟɪɤɭɬɚɧɚ ɢɝɥɟɧɚ ɛɢɨɩɫɢʁɚ ɬɭɦɨɪɫɤɟ ɩɪɨɦɟɧɟ ɧɚ ɛɭɛɪɟɝɭ ɤɨɪɢɫɬɢ ɫɟ ɭ ɫɥɟɞɟʄɢɦ ɢɧɞɢɤɚɰɢʁɚɦɚ: ɩɨɫɬɚɜʂɚʃɟ ɞɢʁɚɝɧɨɡɟ ɪɚɞɢɨɥɨɲɤɢ ɧɟɞɨɜɨʂɧɨ ɞɟɮɢɧɢɫɚɧɟ ɬɭɦɨɪɫɤɟ ɩɪɨɦɟɧɟ, ɯɢɫɬɨɥɨɲɤɟ ɞɢʁɚɝɧɨɡɟ ɫɥɭɱɚʁɧɨ ɨɬɤɪɢɜɟɧɢɯ ɩɪɨɦɟɧɚ ɧɚ ɛɭɛɪɟɝɭ ɤɨɞ ɩɚɰɢʁɟɧɚɬɚ ɤɨʁɢ ɧɢɫɭ ɤɚɧɞɢɞɚɬɢ ɡɚ ɯɢɪɭɪɲɤɨ ɥɟɱɟʃɟ, ɜɟʄ ɡɚ ɚɤɬɢɜɧɨ ɩɪɚʄɟʃɟ ɢɥɢ ɚɛɥɚɬɢɜɧɭ ɬɟɪɚɩɢʁɭ ɢ ɪɚɞɢ ɭɬɜɪђɢɜɚʃɚ ɨɩɬɢɦɚɥɧɟ ɰɢʂɧɟ ɬɟɪɚɩɢʁɟ ɡɚ ɦɟɬɚɫɬɚɬɫɤɢ ɄȻ. Ɉɜɚ ɞɢʁɚɝɧɨɫɬɢɱɤɚ ɩɪɨɰɟɞɭɪɚ ɩɪɚʄɟɧɚ ʁɟ ɦɢɧɢɦɚɥɧɢɦ ɪɢɡɢɤɨɦ ɨɞ ɤɨɦɩɥɢɤɚɰɢʁɚ, ɚ ɢɦɚ ɜɢɫɨɤɭ ɫɟɧɡɢɬɢɜɧɨɫɬ (80-92%) ɢ ɫɩɟɰɢɮɢɱɧɨɫɬ (83-100%) ɡɚ ɞɟɬɟɤɰɢʁɭ ɄȻ117,118. ɍɩɪɤɨɫ ɩɪɢɦɟɧɢ ɫɚɜɪɟɦɟɧɢɯ ɞɢʁɚɝɧɨɫɬɢɱɤɢɯ ɩɪɨɰɟɞɭɪɚ,ʁɟɞɧɚ ɬɪɟʄɢɧɚ ɩɚɰɢʁɟɧɚɬɚ ɭ ɜɪɟɦɟ ɞɢʁɚɝɧɨɡɟ ɢɦɚ ɦɟɬɚɫɬɚɬɫɤɭ ɛɨɥɟɫɬ. ɋ ɨɛɡɢɪɨɦ ɞɚ ɫɄȻ ɩɪɟɞɫɬɚɜʂɚ ɧɚʁɱɟɲʄɭ ɦɟɬɚɫɬɚɬɫɤɭ ɢ ɚɝɪɟɫɢɜɧɭ ɮɨɪɦɭ ɤɚɪɰɢɧɨɦɚ ɛɭɛɪɟɝɚ,ɧɟɨɩɯɨɞɧɢ ɫɭ ɧɨɜɢ ɢ ɩɨɭɡɞɚɧɢ ɞɢʁɚɝɧɨɫɬɢɱɤɢ ɬɟɫɬɨɜɢ ɡɚ ɨɬɤɪɢɜɚʃɟ ɛɨɥɟɫɬɢ ɭ ɩɪɟɦɟɬɚɫɬɚɬɫɤɨɦ ɩɟɪɢɨɞɭ. Ɋɚɧɚ ɞɢʁɚɝɧɨɡɚ ɭ ɮɚɡɢ ɨɪɝɚɧ-ɨɝɪɚɧɢɱɟɧɟ ɛɨɥɟɫɬɢ ɭɞɪɭɠɟɧɚ ʁɟ ɫɚ ɞɨɛɪɨɦ ɩɪɨɝɧɨɡɨɦ, ɚɥɢ ɫɟ ɨɜɚʁ ɬɢɩ ɤɚɪɰɢɧɨɦɚ ɤɚɪɚɤɬɟɪɢɲɟ ɨɞɫɭɫɬɜɨɦ ɪɚɧɢɯ ɫɢɦɩɬɨɦɚ ɢ ɡɧɚɤɨɜɚ ɛɨɥɟɫɬɢ, ɤɚɨ ɢ ɥɚɛɨɪɚɬɨɪɢʁɫɤɢɯ ɚɛɧɨɪɦɚɥɧɨɫɬɢ.Ɉɝɪɚɧɢɱɟɧɟ ɦɨɝɭʄɧɨɫɬɢ ɡɚ ɪɚɧɭ ɞɢʁɚɝɧɨɡɭ ɬɭɦɨɪɚ ɛɭɛɪɟɝɚ ɭɤɚɡɚɥɟ ɫɭ ɧɚ ɧɟɨɩɯɨɞɧɨɫɬ ɪɚɡɜɨʁɚ ɫɟɧɡɢɬɢɜɧɢɯ ɛɢɨɦɚɪɤɟɪɚ ɡɚ ɫɤɪɢɧɢɧɝ ɢ ɩɪɚʄɟʃɟ ɬɭɦɨɪɫɤɢɯ ɩɪɨɦɟɧɚ ɭ ɛɭɛɪɟɝɭ, ɚ ɤɨʁɢ ɛɢ ɦɨɝɥɢ ɞɚ ɭɤɚɠɭ ɧɚ ɩɪɢɪɨɞɭ ɩɪɨɦɟɧɟ ɢ ɧɚɱɢɧ ʃɟɧɨɝ ɥɟɱɟʃɚ.Ȼɢɨɦɚɪɤɟɪɢ ɩɨ ɞɟɮɢɧɢɰɢʁɢ ɩɪɟɞɫɬɚɜʂɚʁɭ ɥɚɤɨ ɦɟɪʂɢɜɟ ɫɭɩɫɬɚɧɰɟ ɤɨʁɟ ɫɟ ɦɨɝɭ ɤɨɪɢɫɬɢɬɢ ɡɚ ɩɪɚʄɟʃɟ ɤɚɤɨ ɧɨɪɦɚɥɧɢɯ, ɬɚɤɨ ɢ ɚɛɧɨɪɦɚɥɧɢɯ ɛɢɨɥɨɲɤɢɯ ɮɭɧɤɰɢʁɚ ɨɪɝɚɧɢɡɦɚ. ɇɚɠɚɥɨɫɬ, ʁɨɲ ɭɜɟɤ ɍȼɈȾ 15 ɧɟ ɩɨɫɬɨʁɢ ɢɞɟɚɥɚɧ ɛɢɨɦɚɪɤɟɪ ɡɚ ɞɢʁɚɝɧɨɡɭ ɤɚɪɰɢɧɨɦɚ ɛɭɛɪɟɝɚ, ɧɢɬɢ ɧɚɱɢɧ ɡɚ ɩɨɩɭɥɚɰɢɨɧɢ ɫɤɪɢɧɢɧɝ ɨɜɟ ɛɨɥɟɫɬɢ119. ɉɨɭɡɞɚɧ ɭɪɢɧɚɪɧɢ ɬɟɫɬ ɡɚ ɤɚɪɰɢɧɨɦ ɛɭɛɪɟɝɚ ɦɨɝɚɨ ɛɢ ɞɚ ɢɦɚ ɡɧɚɱɚʁ ɭ ɫɤɪɢɧɢɧɝɭ ɩɚɰɢʁɟɧɚɬɚ ɫɚ ɜɢɫɨɤɢɦ ɪɢɡɢɤɨɦ ɡɚ ɨɛɨʂɟɜɚʃɟ ɨɞ ɨɜɟ ɜɪɫɬɟ ɬɭɦɨɪɚ ɢ ɩɨɬɟɧɰɢʁɚɥɧɨ ɤɚɨ ɞɨɞɚɬɧɢ ɦɚɪɤɟɪ ɡɚ ɨɞɝɨɜɨɪ ɧɚ ɬɟɪɚɩɢʁɭ ɢ ɩɨɫɬ-ɬɟɪɚɩɢʁɫɤɨ ɩɪɚʄɟʃɟ120. ɉɨɤɚɡɚɧɨ ʁɟ ɞɚ ɭ ɬɭɦɨɪɫɤɨɦ ɬɤɢɜɭ ɫɄȻ ɩɨɫɬɨʁɢ ɩɨɜɟʄɚɧɚ ɟɤɫɩɪɟɫɢʁɚ ɨɞɪɟђɟɧɢɯ ɩɪɨɬɟɢɧɚ. ɇɚ ɨɫɧɨɜɭ ɩɨɬɟɧɰɢʁɚɥɚ ɡɚ ɭɪɢɧɚɪɧɭ ɟɤɫɤɪɟɰɢʁɭ ɨɜɢɯ ɭɫɯɨɞɧɨ ɪɟɝɭɥɢɫɚɧɢɯ ɩɪɨɬɟɢɧɚ, ɢɫɩɢɬɢɜɚɧɨ ʁɟ ɧɟɤɨɥɢɤɨ ɩɨɬɟɧɰɢʁɚɥɧɢɯ ɛɢɨɦɚɪɤɟɪɚ ɨɞ ɡɧɚɱɚʁɚ ɡɚ ɞɢʁɚɝɧɨɡɭ ɫɄȻ: NGAL, KIM-1, AQP-1, ɚɞɢɩɨɮɢɥɢɧ (ADPF). Ɇɟђɭ ɧɚɜɟɞɟɧɢɦ ɛɢɨɦɚɪɤɟɪɢɦɚ ɫɭ ɫɟ ɩɨ ɫɜɨʁɨʁ ɫɟɧɡɢɬɢɜɧɨɫɬɢ ɢ ɫɩɟɰɢɮɢɱɧɨɫɬɢ ɡɚ ɞɢʁɚɝɧɨɡɭ ɫɄȻ ɢɡɞɜɨʁɢɥɢ KIM-1 ɢ AQP-1121. 1.7. Ɇɨɥɟɤɭɥɚɪɧɢ ɦɚɪɤɟɪɢ ɡɧɚɱɚʁɧɢ ɡɚ ɞɢʁɚɝɧɨɡɭ ɤɚɪɰɢɧɨɦɚ ɫɜɟɬɥɢɯ ʄɟɥɢʁɚ ɛɭɛɪɟɝɚ 1.7.1. ɉɪɨɬɟɢɧ-1 ɨɲɬɟʄɟʃɚ ɛɭɛɪɟɝɚ ɉɪɨɬɟɢɧ-1 ɨɲɬɟʄɟʃɚ ɛɭɛɪɟɝɚ (ɟɧɝɥ. ɫɤɪ. KIM-1–kidney injury molecule-1) ʁɟ ɬɢɩ 1 ɬɪɚɧɫɦɟɦɛɪɚɧɫɤɨɝ ɩɪɨɬɟɢɧɚ, ɤɨʁɢ ʁɟ ɩɪɜɢ ɩɭɬ ɢɡɨɥɨɜɚɨ ɢ ɨɩɢɫɚɨ Ischimura ɢ ɫɚɪ. 1998. ɝɨɞɢɧɟ122. Ɉɡɧɚɱɚɜɚ ɫɟ ʁɨɲ ɢ ɤɚɨ HAVCR-1 (ɟɧɝɥ. ɫɤɪ. Hepatitis A Virus Cellular Receptor–1), ʁɟɪ ɫɟ ɟɤɫɩɪɢɦɢɪɚ ɧɚ ɯɟɩɚɬɨɰɢɬɢɦɚ, ɨɥɚɤɲɚɜɚʁɭʄɢ ɭɥɚɡ ɜɢɪɭɫɚ ɭ ʄɟɥɢʁɭ ɢ ɤɚɨ TIM-1(ɟɧɝɥ. ɫɤɪ.T cell immunoglobulin mucin domains-1) ʁɟɪ ɫɟ ɟɤɫɩɪɢɦɢɪɚ ɭ ɧɢɫɤɨɦ ɧɢɜɨɭ ɢ ɧɚ ɫɭɛɩɨɩɭɥɚɰɢʁɢ ɚɤɬɢɜɢɪɚɧɢɯ Ɍ ʄɟɥɢʁɚ. Ƚɟɧ ɡɚ KIM-1 ʁɟ ɥɨɰɢɪɚɧ ɧɚ ɯɪɨɦɨɡɨɦɭ 5q ɢ ɤɨɞɢɪɚ ɬɢɩ 1 ʄɟɥɢʁɫɤɨɝ ɦɟɦɛɪɚɧɫɤɨɝ ɝɥɢɤɨɩɪɨɬɟɢɧɚ, ɤɨɝɚ ɱɢɧɟ ɟɤɬɪɚɰɟɥɭɥɚɪɧɢ ɢɥɢ ɟɤɬɨɞɨɦɟɧ, ɬɪɚɧɫɦɟɦɛɪɚɧɫɤɢ ɞɨɦɟɧ ɢ ɰɢɬɨɩɥɚɡɦɚɬɫɤɢ ɞɨɦɟɧ, ɱɢʁɚ ɦɨɥɟɤɭɥɫɤɚ ɬɟɠɢɧɚɢɡɧɨɫɢ 104 kDa. ɉɨɞ ɞɟʁɫɬɜɨɦ ɟɧɡɢɦɚ ɦɟɬɚɥɨɩɪɨɬɟɢɧɚɡɟ ɞɨɥɚɡɢ ɞɨ ɰɟɩɚʃɚ ʃɟɝɨɜɨɝ ɟɤɫɬɪɚɰɟɥɭɥɚɪɧɨɝ ɞɨɦɟɧɚ ɢ ɫɟɤɪɟɰɢʁɟ ɭ ɭɪɢɧ, ɝɞɟ ɫɟ ɦɨɠɟ ɞɟɬɟɤɬɨɜɚɬɢ ɤɚɨ 90 kDa ɬɟɠɚɤ ɫɨɥɭɛɢɥɧɢ ɩɪɨɬɟɢɧ, ɨɡɧɚɱɟɧ ɤɚɨ ɭɪɢɧɚɪɧɢ KIM-1 (uKIM-1)123. KIM-1 ɫɟ ɧɟ ɟɤɫɩɪɢɦɢɪɚ ɭ ɡɞɪɚɜɨɦ ɛɭɛɪɟɠɧɨɦ ɬɤɢɜɭ. ɍ ɫɬɚʃɢɦɚ ɢɫɯɟɦɢʁɫɤɨɝ ɢɥɢ ɬɨɤɫɢɱɧɨɝ ɛɭɛɪɟɠɧɨɝ ɨɲɬɟʄɟʃɚ ɞɨɥɚɡɢ ɞɨ ʃɟɝɨɜɟ ɪɚɩɢɞɧɟ ɟɤɫɩɪɟɫɢʁɟ ɧɚ ɚɩɢɤɚɥɧɨʁ ɦɟɦɛɪɚɧɢ ɩɪɨɤɫɢɦɚɥɧɢɯ ɬɭɛɭɥɚ. ɋɟɥɟɤɬɢɜɧɚ ɟɤɫɩɪɟɫɢʁɚ KIM-1 ɧɚ ɨɲɬɟʄɟɧɢɦ ɬɭɛɭɥɫɤɢɦ ɟɩɢɬɟɥɧɢɦ ʄɟɥɢʁɚɦɚ ɩɪɟɞɫɬɚɜʂɚ ɫɢɝɭɪɚɧ ɩɨɞɫɬɢɰɚʁ ɡɚ ɭɩɨɬɪɟɛɭ KIM-1 ɤɚɨ ɦɚɪɤɟɪɚ ɛɭɛɪɟɠɧɨɝ ɨɲɬɟʄɟʃɚ, ɩɪɢ ɱɟɦɭ ɧɢɜɨ uKIM-1 ɫɬɪɨɝɨ ɤɨɪɟɥɢɪɚ ɫɚ ʃɟɝɨɜɨɦ ɟɤɫɩɪɟɫɢʁɨɦ ɭ ɛɭɛɪɟɠɧɨɦ ɬɤɢɜɭ124. ɉɨɫɬɨʁɢ ɧɟɤɨɥɢɤɨ ɤɚɪɚɤɬɟɪɢɫɬɢɤɚ KIM-1 ɡɛɨɝ ɱɟɝɚ ɫɟ ɜɟɪɭʁɟ ɞɚ ɛɢ ɨɜɚʁ ɩɪɨɬɟɢɧ ɦɨɝɚɨ ɛɢɬɢ ɢɞɟɚɥɧɢ ɛɢɨɦɚɪɤɟɪ ɛɭɛɪɟɠɧɨɝ ɨɲɬɟʄɟʃɚ:ɨɞɫɭɫɬɜɨ ɟɤɫɩɪɟɫɢʁɟ KIM-1 ɭ ɡɞɪɚɜɨɦ ɛɭɛɪɟɝɭ, ʃɟɝɨɜɚ ɡɧɚɱɚʁɧɚ ɭɫɯɨɞɧɚ ɪɟɝɭɥɚɰɢʁɚ ɢ ɜɟɡɢɜɚʃɟ ɧɚ ɚɩɢɤɚɥɧɨʁ ɦɟɦɛɪɚɧɢ ɩɪɨɤɫɢɦɚɥɧɨɝ ɬɭɛɭɥɚ, ɩɟɪɡɢɫɬɢɪɚʃɟ ɧɚ ɟɩɢɬɟɥɧɢɦ ʄɟɥɢʁɚɦɚ ɞɨ ʃɢɯɨɜɨɝ ɤɨɦɩɥɟɬɧɨɝ ɨɩɨɪɚɜɤɚ, ɪɚɩɢɞɧɨ ɢ ɡɧɚɱɚʁɧɨ ɰɟɩɚʃɟ ɟɤɬɨɞɨɦɟɧɚ ɢ ʃɟɝɨɜɚ ɫɬɚɛɢɥɧɨɫɬ ex vivo ɧɚ ɫɨɛɧɨʁ ɬɟɦɩɟɪɚɬɭɪɢ ɢ ɱɢʃɟɧɢɰɚ ɞɚɧɢ ʁɟɞɚɧ ɞɪɭɝɢ ɨɪɝɚɧ ɧɟ ɟɤɫɩɪɢɦɢɪɚ KIM-1 ɭ ɦɟɪɢ ɤɨʁɚ ɛɢ ɦɨɝɥɚ ɞɚ ɭɬɢɱɟ ɧɚ ʃɟɝɨɜɭ ɛɭɛɪɟɠɧɭ ɟɤɫɤɪɟɰɢʁɭ125,126. Ʉɨɧɰɟɧɬɪɚɰɢʁɚ KIM-1 ɭ ɭɪɢɧɭ ɨɞɪɟђɭʁɟ ɫɟ ɢɡ ɫɜɟɠɟɝ ɭɡɨɪɤɚ ɭɪɢɧɚ ɢɥɢ ɭɡɨɪɤɚ ɡɚɦɪɡɧɭɬɨɝ ɧɚ -80̊C, ɦɚɤɫɢɦɚɥɧɨ 4 ɱɚɫɚ ɧɚɤɨɧ ɭɡɨɪɤɨɜɚʃɚ. Ⱦɨɞɚɬɚɤ ɢɧɯɢɛɢɬɨɪɚ ɩɪɨɬɟɚɡɟ ɢɥɢ ɰɟɧɬɪɢɮɭɝɢɪɚʃɟ ɧɢɫɭ ɧɟɨɩɯɨɞɧɢ. ȳɟɞɧɨɦ ɡɚɦɪɡɧɭɬ ɭɡɨɪɚɤ ɦɨɠɟ ɫɟ ɱɭɜɚɬɢ ɧɚʁɦɚʃɟ 1,5 ɍȼɈȾ 16 ɝɨɞɢɧɭ ɛɟɡ ɭɬɢɰɚʁɚ ɧɚ ɫɦɚʃɟʃɟ ɤɨɧɰɟɧɬɪɚɰɢʁɟ KIM-1 ɭ ʃɟɦɭ127. Ⱦɨɛɢʁɟɧɚ ɤɨɧɰɟɧɬɪɚɰɢʁɚ ɫɟ ɢɡɪɚɠɚɜɚ ɭ ng/ml ɤɚɨ ɚɩɫɨɥɭɬɧɚ ɜɪɟɞɧɨɫɬ ɢ ɤɚɨ ɤɨɪɢɝɨɜɚɧɚ ɜɪɟɞɧɨɫɬ ɩɪɟɦɚ ɤɨɧɰɟɧɬɪɚɰɢʁɢ ɤɪɟɚɬɢɧɢɧɚ ɭ ɭɡɨɪɤɭ ɭɪɢɧɚ ɢ ɢɡɪɚɠɚɜɚ ɭ ng/mg ɤɪɟɚɬɢɧɢɧɚ. ɇɨɪɦɚɥɢɡɚɰɢʁɚ ɜɪɟɞɧɨɫɬɢ ɫɟ ɜɪɲɢ ɭ ɰɢʂɭ ɤɨɪɟɤɰɢʁɟ ɩɪɟɦɚ ɤɥɢɪɟɧɫɭ ɤɪɟɚɬɢɧɢɧɚ ɢ ɜɨɥɭɦɟɧɭ ɢɡɥɭɱɟɧɨɝ ɭɪɢɧɚ128. Ɉɞɪɟђɢɜɚʃɟ ɤɨɧɰɟɧɬɪɚɰɢʁɟ uKIM-1 ɩɪɟɞɫɬɚɜʂɚ ɧɟɢɧɜɚɡɢɜɧɢ ɢ ɫɟɧɡɢɬɢɜɧɢ ɦɟɬɨɞ ɡɚ ɩɪɨɰɟɧɭ ɛɭɛɪɟɠɧɨɝ ɨɲɬɟʄɟʃɚ ɢ ɡɚ ɩɪɚʄɟʃɟ ɬɟɪɚɩɢʁɫɤɢɯ ɟɮɟɤɚɬɚ. ɍ ɫɬɭɞɢʁɢ ɢɫɩɢɬɢɜɚʃɚ ɧɟɮɪɨɬɨɤɫɢɱɧɨɫɬɢ,ɧɢɜɨ uKIM-1 ʁɟ ɡɧɚɱɚʁɧɨ ɪɚɧɢʁɟ ɪɚɫɬɚɨ ɭ ɩɨɪɟђɟʃɭ ɫɚ ɫɟɪɭɦɫɤɢɦ ɤɨɧɰɟɧɬɪɚɰɢʁɚɦɚ ɭɪɟɟ ɢ ɤɪɟɚɬɢɧɢɧɚ. ɋɥɢɱɧɢ ɪɟɡɭɥɬɚɬɢ ɫɭ ɞɨɛɢʁɟɧɢ ɭ ɦɨɞɟɥɭ ɢɫɯɟɦɢʁɫɤɨ/ɪɟɩɟɪɮɭɡɢɨɧɨɝ ɨɲɬɟʄɟʃɚ, ɩɪɢ ɱɟɦɭ 10-ɦɢɧɭɬɧɨ ɢɡɥɚɝɚʃɟ ɢɫɯɟɦɢʁɢ ɢɡɚɡɢɜɚ ɫɢɝɧɢɮɢɤɚɧɬɚɧ ɩɨɪɚɫɬ uKIM-1, ɛɟɡ ɩɪɨɦɟɧɟ ɭ ɤɨɧɰɟɧɬɪɚɰɢʁɢ ɫɟɪɭɦɫɤɨɝ ɤɪɟɚɬɢɧɢɧɚ, ɤɥɢɪɟɧɫɤɚ ɤɪɟɚɬɢɧɢɧɚ ɢ ɩɪɨɬɟɢɧɭɪɢʁɟ129. ɍ ɟɤɩɟɪɢɦɟɧɬɢɦɚ ɧɚ ɠɢɜɨɬɢʃɚɦɚ ɩɨɜɟʄɚɧɚ ɟɤɫɩɪɟɫɢʁɚ KIM-1 ɧɚ ɩɪɨɤɫɢɦɚɥɧɢɦ ɬɭɛɭɥɢɦɚ ɧɚђɟɧɚ ʁɟ ɧɚɤɨɧ ɢɫɯɟɦɢʁɫɤɨ-ɪɟɩɟɪɮɭɡɢɨɧɨɝ ɨɲɬɟʄɟʃɚ, ɢɡɥɚɝɚʃɚ ɬɨɤɫɢɱɧɨɦ ɞɟʁɫɬɜɭ ʁɨɞɧɢɯ ɤɨɧɬɪɚɫɬɧɢɯ ɫɪɟɞɫɬɚɜɚ, ɤɚɞɦɢʁɭɦɚ, ɰɢɫɩɥɚɬɢɧɟ, ɜɚɧɤɨɦɢɰɢɧɚ, ɝɟɧɬɚɦɢɰɢɧɚ, ɠɢɜɟ ɢ ɨɥɨɜɚ, ɤɨɞ ɩɨɥɢɰɢɫɬɢɱɧɟ ɛɨɥɟɫɬɢ ɛɭɛɪɟɝɚ, ɩɪɨɬɟɢɧɭɪɢʁɟ ɩɪɟɥɢɜɚʃɚ130,131,132.ɍ ɯɭɦɚɧɨʁ ɩɨɩɭɥɚɰɢʁɢ ɭɫɯɨɞɧɚ ɪɟɝɭɥɚɰɢʁɚ KIM-1, ɡɚ ɤɨɝɚ ɫɟ ɩɪɟɬɩɨɫɬɚɜʂɚ ɞɚ ɛɢ ɦɨɝɚɨ ɛɢɬɢ ɚɞɯɟɡɢɨɧɢ ɦɨɥɟɤɭɥ ɟɩɢɬɟɥɧɢɯ ʄɟɥɢʁɚ, ɧɚђɟɧɚ ʁɟ ɤɨɞ ɩɚɰɢʁɟɧɚɬɚ ɫɚ: ɤɚɪɰɢɧɨɦɨɦ ɛɭɛɪɟɝɚ, IgA ɧɟɮɪɨɩɚɬɢʁɨɦ, ɭɪɚɬɧɨɦ ɧɟɮɪɨɩɚɬɢʁɨɦ, ɚɤɭɬɧɨɦ ɢ ɯɪɨɧɢɱɧɨɦ ɛɭɛɪɟɠɧɨɦ ɢɧɫɭɮɢɰɢʁɟɧɰɢʁɨɦ, ɚɤɭɬɧɢɦ ɢ ɯɪɨɧɢɱɧɢɦ ɬɭɛɭɥɫɤɢɦ ɨɲɬɟʄɟʃɢɦɚ, ɚɥɨɝɪɚɮɬ ɧɟɮɪɨɩɚɬɢʁɨɦ133,134. 1.7.1.1. KIM-1 ɢ ɚɤɭɬɧɨ ɛɭɛɪɟɠɧɨ ɨɲɬɟʄɟʃɟ Ɇɚɞɚ ɫɟɪɭɦɫɤɢ ɤɪɟɬɢɧɢɧ ɩɪɟɞɫɬɚɜʂɚ ɫɬɚɧɞɚɪɞɧɢ ɦɚɪɤɟɪ ɡɚ ɞɟɬɟɤɰɢʁɭ ɛɭɛɪɟɠɧɨɝ ɨɲɬɟʄɟʃɚ, ɩɨɤɚɡɚɥɨ ɫɟ ɞɚ ʁɟ ɨɧ ɧɟɞɨɜɨʂɧɨ ɫɟɧɡɢɬɢɜɚɧ ɡɚ ʃɟɝɨɜɭ ɪɚɧɭ ɞɢʁɚɝɧɨɡɭ. Ɋɟɡɭɥɬɚɬɢ ɫɬɭɞɢʁɚ ɫɭ ɩɨɤɚɡɚɥɢ ɞɚ ɧɟɤɨɥɢɤɨ ɩɪɨɬɟɢɧɚ ɢɡ ɭɪɢɧɚ, ɭɤʂɭɱɭʁɭʄɢ ɢ KIM-1, ɦɨɝɭ ɩɪɞɫɬɚɜʂɚɬɢ ɪɚɧɟ ɦɚɪɤɟɪɟ ɚɤɭɬɧɨɝ ɨɲɬɟʄɟʃɚ ɛɭɛɪɟɝɚ135.ɍ ɫɬɭɞɢʁɢ Liangos ɢ ɫɚɪ. ɞɨɤɚɡɚɧɨ ʁɟ ɞɚ ɫɭ ɩɚɰɢʁɟɧɬɢ ɫɚ ɚɤɭɬɧɢɦ ɛɭɛɪɟɠɧɢɦ ɨɲɬɟʄɟʃɟɦ ɢ ɧɚʁɜɢɲɨɦ ɜɪɟɞɧɨɲʄɭKIM-1 ɭ ɭɪɢɧɭ, ɢɦɚɥɢ 3,2 ɩɭɬɚ ɜɟʄɭ ɫɬɨɩɭ ɪɚɡɜɨʁɚ ɫɦɪɬɧɨɝ ɢɫɯɨɞɚ ɢɥɢ ɩɨɬɪɟɛɟ ɡɚ ɥɟɱɟʃɟɦ ɞɢʁɚɥɢɡɨɦ ɭ ɨɞɧɨɫɭ ɧɚ ɩɚɰɢʁɟɧɬɟ ɫɚ ɧɚʁɧɢɠɨɦ ɤɨɧɰɟɧɬɪɚɰɢʁɨɦ KIM-1 ɭ ɭɪɢɧɭ136. In situɯɢɛɪɢɞɢɡɚɰɢʁɨɦ ɢ ɢɦɭɧɨɯɢɫɬɨɯɟɦɢʁɫɤɢɦ ɢɫɩɢɬɢɜɚʃɢɦɚ, ɩɨɤɚɡɚɧɨ ʁɟ ɞɚ ɫɟ KIM-1 ɟɤɫɩɪɢɦɢɪɚ ɧɚ ɞɟɞɢɮɟɪɟɧɰɢɪɚɧɢɦ ɢ ɪɟɝɟɧɟɪɢɫɚɧɢɦ ɩɪɨɤɫɢɦɚɥɧɢɦ ɬɭɛɭɥɚɪɧɢɦ ɟɩɢɬɟɥɧɢɦ ʄɟɥɢʁɚɦɚ ɧɚɤɨɧ ɢɫɯɟɦɢʁɫɤɨɝ ɢɥɢ ɬɨɤɫɢɱɧɨɝ ɨɲɬɟʄɟʃɚ. ɉɨɤɚɡɚɧɨ ʁɟ ɞɚ ɫɟ KIM-1 ɟɤɫɩɪɢɦɢɪɚ ɡɚʁɟɞɧɨ ɫɚ ɛɪɨɦɨɞɟɨɤɫɢɭɪɢɞɢɧɨɦ, ɦɚɪɤɟɪɨɦ ɩɪɨɥɢɮɟɪɚɰɢʁɟ ɢ ɟɥɚɫɬɢɧɨɦ, ɦɚɪɤɟɪɨɦ ɞɟɞɢɮɟɪɟɧɰɢʁɚɰɢʁɟ, ɡɛɨɝ ɱɟɝɚ ɦɨɠɟ ɢɦɚɬɢ ɭɥɨɝɭ ɭ ɩɪɨɰɟɫɭ ɪɟɝɟɧɟɪɚɰɢʁɟ ɬɭɛɭɥɫɤɢɯ ɟɩɢɬɟɥɧɢɯ ʄɟɥɢʁɚ. ɋɬɪɭɤɬɭɪɧɨ, KIM-1 ɩɪɟɞɫɬɚɜʂɚ ɚɞɯɟɡɢɨɧɢ ɦɨɥɟɤɭɥ ɤɨʁɢ ɭɱɟɫɬɜɭʁɟ ɭ ʄɟɥɢʁɫɤɨɦ ɤɪɟɬɚʃɭ, ɩɪɨɥɢɮɟɪɚɰɢʁɢ ɢ ɞɟɞɢɮɟɪɟɧɰɢʁɚɰɢʁɢ, ɩɪɢ ɱɟɦɭ ʁɟ ɫɜɚɤɚ ɬɪɚɧɡɢɰɢʁɚ ɧɨɪɦɚɥɧɢɯ ɟɩɢɬɟɥɧɢɯ ʄɟɥɢʁɚ ɭ ɞɟɞɢɮɟɪɟɧɰɢɪɚɧɟ ɭɞɪɭɠɟɧɚ ɫɚ ɡɧɚɱɚʁɧɨɦ ɭɫɯɨɞɧɨɦ ɟɤɫɩɪɟɫɢʁɨɦ KIM-1137. ɇɟɞɚɜɧɚ ɨɬɤɪɢʄɚ Ichimura ɢ ɫɚɪ. ɭɤɚɡɭʁɭ ɞɚ KIM-1 ɩɪɟɞɫɬɚɜʂɚ ɪɟɰɟɩɬɨɪ ɡɚ ɮɨɫɮɚɬɢɞɢɥɫɟɪɢɧ, ɲɬɨ ɟɩɢɬɟɥɧɢɦ ʄɟɥɢʁɚɦɚ ɞɚʁɟ ɤɚɪɚɤɬɟɪɢɫɬɢɤɟ ɮɚɝɨɰɢɬɧɢɯ ʄɟɥɢʁɚ. Ɏɭɧɤɰɢɨɧɚɥɧɨ, KIM-1 ʁɟ ɫɩɨɫɨɛɚɧ ɞɚ ɮɚɝɨɰɢɬɭʁɟ ɚɩɨɩɬɨɬɢɱɧɟ ɢ ɧɟɤɪɨɬɢɱɧɟ ʄɟɥɢʁɟ ɍȼɈȾ 17 ɢɡ ɥɭɦɟɧɚ ɬɭɛɭɥɚ, ɱɢɦɟ ɫɭɩɪɢɦɢɪɚ ɚɭɬɨɢɦɭɧɢ ɨɞɝɨɜɨɪ ɢ ɩɪɨɞɭɤɰɢʁɭ ɩɪɨɢɧɮɥɚɦɚɬɨɪɧɢɯ ɰɢɬɨɤɢɧɚ. ɋɦɚɬɪɚ ɫɟ ɞɚ ɧɚ ɬɚʁ ɧɚɱɢɧ KIM-1 ɭɱɟɫɬɜɭʁɟ ɭ ɩɪɨɰɟɫɢɦɚ ɨɩɨɪɚɜɤɚ ɢ ɡɚɦɟɧɟ ɟɩɢɬɟɥɚ138. 1.7.1.2.KIM-1 ɢ ɯɪɨɧɢɱɧɚ ɛɭɛɪɟɠɧɚ ɛɨɥɟɫɬ Ɂɚ ɪɚɡɥɢɤɭ ɨɞ ɞɨɤɚɡɚɧɟ ɩɪɨɬɟɤɬɢɜɧɟ ɮɭɧɤɰɢʁɟ KIM-1 ɤɨɞ ɚɤɭɬɧɨɝ ɛɭɛɪɟɠɧɨɝ ɨɲɬɟʄɟʃɚ, ɩɨɫɬɨʁɟ ɛɪɨʁɧɢ ɞɨɤɚɡɢ ɨ ʃɟɝɨɜɨʁ ɭɥɨɡɢ ɭ ɯɪɨɧɢɱɧɨɦ ɨɲɬɟʄɟʃɭ ɤɨɞ ɯɪɨɧɢɱɧɟ ɛɭɛɪɟɠɧɟ ɛɨɥɟɫɬɢ (ɏȻȻ). KIM-1 ɫɟ ɟɤɫɩɪɢɦɢɪɚ ɧɚ ɞɟɞɢɮɟɪɟɧɬɨɜɚɧɢɦ ɬɭɛɭɥɚɪɧɢɦ ɟɩɢɬɟɥɧɢɦ ʄɟɥɢʁɚɦɚ ɤɚɨ ɢ ɭ ɚɤɭɬɧɨɦ ɛɭɛɪɟɠɧɨɦ ɨɲɬɟʄɟʃɭ, ɭɤɚɡɭʁɭʄɢ ɧɚ ʃɟɝɨɜɭ ɭɥɨɝɭ ɭ ɬɭɛɭɥɫɤɨʁ ɮɢɛɪɨɡɢ. ɉɨɤɚɡɚɧɨ ʁɟ ɞɚ ʃɟɝɨɜɚ ɟɤɫɩɪɟɫɢʁɚ ɤɨɪɟɥɢɪɚ ɫɚ ɧɢɜɨɨɦ ɬɤɢɜɧɨɝ ɨɫɬɟɨɩɨɧɬɢɧɚ ɢ α- ɝɥɚɬɤɨɦɢɲɢʄɧɨɝ ɚɤɬɢɧɚ, ɤɨʁɢ ɩɪɟɞɫɬɚɜʂɚʁɭ ɦɚɪɤɟɪɟ ɬɭɛɭɥɨɢɧɬɟɪɫɬɢɰɢʁɫɤɨɝ ɨɲɬɟʄɟʃɚ139. ɍ ɫɬɭɞɢʁɢ VanTimmeren ɢ ɫɚɪ. ɩɨɤɚɡɚɧɚ ʁɟ ɩɨɡɢɬɢɜɧɨɫɬ ɧɚ KIM-1 ɧɚ ɞɟɞɢɮɟɪɟɧɬɨɜɚɧɢɦ ɩɪɨɤɫɢɦɚɥɧɢɦ ɬɭɛɭɥɫɤɢɦ ʄɟɥɢʁɚɦɚ, ɲɬɨ ʁɟ ɤɨɪɟɥɢɪɚɥɨ ɫɚ ɬɭɛɭɥɨ-ɢɧɬɟɪɫɬɢɰɢʁɫɤɨɦ ɮɢɛɪɨɡɨɦ ɢ ɢɧɮɥɚɦɚɰɢʁɨɦ. Ʉɨɧɰɟɧɬɪɚɰɢʁɚ KIM-1 ɭ ɭɪɢɧɭ ʁɟ ɤɨɪɟɥɢɪɚɥɚ ɫɚ ʃɟɝɨɜɨɦ ɬɤɢɜɧɨɦ ɟɤɫɩɪɟɫɢʁɨɦ140. Ⱥɧɚɥɢɡɨɦ ɩɚɰɢʁɟɧɚɬɚ ɫɚ ɧɟɞɢʁɚɛɟɬɟɫɧɨɦ ɛɭɛɪɟɠɧɨɦ ɛɨɥɟɫɬɢ, ɩɨɤɚɡɚɧɨ ʁɟ ɞɚ ɧɢɜɨ uKIM-1 ɪɚɫɬɟ ɫɚ ɩɪɨɬɟɢɧɭɪɢʁɨɦ ɚ ɫɦɚʃɭʁɟ ɫɟ ɧɚ ɩɪɢɦɟɧɭ ɚɧɬɢɩɪɨɬɟɢɧɭɪɢɱɤɟ ɬɟɪɚɩɢʁɟ, ɲɬɨ ɭɤɚɡɭʁɟ ɧɚ ɩɨɜɟɡɚɧɨɫɬ ɩɪɨɬɟɢɧɭɪɢʁɟ ɫɚ ɩɪɨɤɫɢɦɚɥɧɢɦ ɬɭɛɭɥɫɤɢɦ ɨɲɬɟʄɟʃɟɦ, ɲɬɨ ʁɟ ɤɜɚɧɬɢɮɢɤɨɜɚɧɨ ɨɞɪɟђɢɜɚʃɟɦ ɤɨɧɰɟɧɬɪɚɰɢʁɟ KIM-1 ɭ ɭɪɢɧɭ141. 1.7.1.3. KIM-1 ɢ ɬɪɚɧɫɩɥɚɧɬɢɪɚɧ ɛɭɛɪɟɝ ɂɫɯɟɦɢʁɫɤɨ/ɪɟɩɟɪɮɭɡɢɨɧɨ ɨɲɬɟʄɟʃɟ ʁɟ ɧɟɢɡɛɟɠɚɧ ɞɨɝɚђɚʁ ɭ ɬɪɚɧɫɩɥɚɧɬɢɪɚɧɨɦ ɛɭɛɪɟɝɭ ɢ ɩɪɚʄɟɧ ʁɟ ɬɭɛɭɥɫɤɢɦ ɨɲɬɟʄɟʃɟɦ ɢ ɩɨɜɟʄɚɧɢɦ ɪɢɡɢɤɨɦ ɨɞ ɚɤɭɬɧɨɝ ɨɞɛɚɰɢɜɚʃɚ. ȿɤɫɩɪɟɫɢʁɚ KIM-1 ɭ ɬɤɢɜɭ ɛɭɛɪɟɠɧɨɝ ɚɥɨɝɪɚɮɬɚ ʁɟ ɫɟɧɡɢɬɢɜɧɢʁɢ ɦɚɪɤɟɪ ɡɚ ɞɟɬɟɤɰɢʁɭ ɪɚɧɨɝ ɬɭɛɭɥɫɤɨɝ ɨɲɬɟʄɟʃɚ ɭ ɩɨɪɟђɟʃɭ ɫɚ ɯɢɫɬɨɥɨɲɤɢɦ ɧɚɥɚɡɨɦ. ɉɨɡɢɬɢɜɧɨɫɬ ɧɚ KIM-1 ɭ ɩɪɨɤɫɢɦɚɥɧɢɦ ɬɭɛɭɥɢɦɚ ɤɨɪɟɥɢɪɚ ɫɚ ɫɬɟɩɟɧɨɦ ɨɲɬɟʄɟʃɚ ɢ ɩɪɟɞɫɬɚɜʂɚ ɦɟɪɭ ɝɭɛɢɬɤɚ ɮɭɧɤɰɢʁɟ ɚɥɨɝɪɚɮɬɚ. ɇɢɜɨ ɟɤɫɩɪɟɫɢʁɟ KIM-1 ɭ ɛɢɨɩɬɢɪɚɧɨɦ ɬɤɢɜɭ ɚɥɨɝɪɚɮɬɚ ɦɨɠɟ ɭɤɚɡɢɜɚɬɢ ɧɚ ɩɨɬɟɧɰɢʁɚɥ ɡɚ ɨɩɨɪɚɜɚɤ ɛɭɛɪɟɠɧɟ ɮɭɧɤɰɢʁɟ ɭ ɩɪɜɢɯ 18 ɦɟɫɟɰɢ ɧɚɤɨɧ ɬɪɚɧɫɩɥɚɧɬɚɰɢʁɟ. Ɇɟђɭɬɢɦ, ɞɭɝɨɪɨɱɧɢɦ ɩɪɚʄɟʃɟɦ ɨɜɢɯ ɛɨɥɟɫɧɢɤɚ ɞɨɤɚɡɚɧɨ ʁɟ ɞɚ ʁɟ ɜɢɫɨɤɚ ɭɪɢɧɚɪɧɚ ɤɨɧɰɟɧɬɪɚɰɢʁɚKIM-1 ɛɢɥɚ ɭɞɪɭɠɟɧɚ ɫɚ ɧɢɠɢɦ ɤɥɢɪɟɧɫɨɦ ɤɪɟɚɬɢɧɢɧɚ, ɜɟʄɨɦ ɩɪɨɬɟɢɧɭɪɢʁɨɦ ɢ ɫɬɚɪɢʁɨɦ ɠɢɜɨɬɧɨɦ ɞɨɛɢ ɞɨɧɨɪɚ ɢ ɞɚ ɩɪɟɞɫɬɚɜʂɚ ɧɟɡɚɜɢɫɧɢ ɩɪɟɞɢɤɬɨɪ ɥɨɲɟ ɩɪɨɝɧɨɡɟ ɢ ɝɭɛɢɬɤɚ ɝɪɚɮɬɚ142. Zhang ɫɚ ɫɚɪ. ʁɟ ɩɨɤɚɡɚɨ ɞɚ ɩɪɢ ɩɪɨɬɨɤɨɥɚɪɧɢɦ ɛɢɨɩɫɢʁɚɦɚ ɭ 28% ɫɥɭɱɚʁɟɜɚ ɧɚђɟɧɚ ʁɟ ɮɨɤɚɥɧɚ ɩɨɡɢɬɢɜɧɨɫɬ ɧɚ KIM-1, ɛɟɡ ɯɢɫɬɨɥɨɲɤɢɯ ɩɨɤɚɡɚɬɟʂɚ ɬɭɛɭɥɫɤɨɝ ɨɲɬɟʄɟʃɚ, ɚ ɭ 100% ɛɢɨɩɫɢʁɚ ɛɭɛɪɟɠɧɨɝ ɝɪɚɮɬɚ ɩɚɰɢʁɟɧɚɬɚ ɫɚ ɫɧɢɠɟɧɨɦ ɛɭɛɪɟɠɧɨɦ ɮɭɧɤɰɢʁɨɦ ɢ ɯɢɫɬɨɥɨɲɤɢɦ ɩɪɨɦɟɧɚɦɚ ɤɨʁɟ ɭɤɚɡɭʁɭ ɧɚ ɬɭɛɭɥɫɤɨ ɨɲɬɟʄɟʃɟ. KIM-1 ɟɤɫɩɪɟɫɢʁɚ ʁɟ ɛɢɥɚ ʁɟ ɭ ɞɢɪɟɤɬɧɨʁ ɤɨɪɟɥɚɰɢʁɢ ɫɚ ɧɢɜɨɢɦɚ ɫɟɪɭɦɫɤɟ ɭɪɟɟ ɢ ɤɪɟɚɬɢɧɢɧɚ, ɚ ɭ ɢɧɜɟɪɡɧɨʁ ɤɨɪɟɥɚɰɢʁɢ ɫɚ ɫɬɨɩɨɦ ɝɥɨɦɟɪɭɥɫɤɟ ɮɢɥɬɪɚɰɢʁɟ143. ɍȼɈȾ 18 1.7.1.4.KIM-1 ɢ ɤɚɪɰɢɧɨɦ ɛɭɛɪɟɝɚ ɋɜɟɬɥɨʄɟɥɢʁɫɤɢ ɤɚɪɰɢɧɨɦ ɛɭɛɪɟɝɚ ʁɟ ɭɞɪɭɠɟɧ ɫɚ ɩɪɨɤɫɢɦɚɥɧɨɦ ɬɭɛɭɥɫɤɨɦ ʄɟɥɢʁɫɤɨɦ ɞɟɞɢɮɟɪɟɧɰɢʁɚɰɢʁɨɦ ɢ ɜɢɫɨɤɨɦ ɟɤɫɩɪɟɫɢʁɨɦ KIM-1. ɂ ɭ ɫɥɭɱɚʁɟɜɢɦɚ ɤɚɞɚ ɫɭ ɬɭɦɨɪɫɤɟ ʄɟɥɢʁɟ ɧɟɝɚɬɢɜɧɟ ɧɚ KIM-1, ɫɭɫɟɞɧɟ ɬɭɛɭɥɫɤɟ ʄɟɥɢʁɟ ɦɨɝɭ ɩɨɤɚɡɢɜɚɬɢ ʃɟɝɨɜɭ ɟɤɫɩɪɟɫɢʁɭ. ɋɦɚɬɪɚ ɫɟ ɞɚ ɨɜɟ ʄɟɥɢʁɟ ɦɨɝɭ ɛɢɬɢ ɤɨɦɩɪɢɦɨɜɚɧɟ ɨɞ ɫɬɪɚɧɟ ɬɭɦɨɪɫɤɢɯ ʄɟɥɢʁɚ ɢ ɩɨɫɥɟɞɢɱɧɨ ɩɨɩɪɢɦɢɬɢ ɞɟɞɢɮɟɪɟɧɬɨɜɚɧ ɮɟɧɨɬɢɩ ɢɥɢ ɦɨɝɭ ɩɨɫɬɚɬɢ ɢɫɯɟɦɢɱɧɟ. ɋ ɨɛɡɢɪɨɦ ɞɚ ʁɟ KIM-1 ɭɤʂɭɱɟɧ ɭ ɢɦɭɧɫɤɢ ɨɞɝɨɜɨɪ, ɚ ɞɚ ʁɟ ɄȻɭ ɨɫɧɨɜɢ ɢɦɭɧɨɝɟɧɢ ɬɭɦɨɪ, ɦɨɝɭʄɟ ʁɟ ɞɚ KIM-1 ɢɦɚ ɭɥɨɝɭ ɭ ɦɨɞɭɥɚɰɢʁɢ ɬɭɦɨɪɫɤɟ ɢɦɭɧɨɝɟɧɨɫɬɢ144. Ⱦɨ ɫɚɞɚ ɫɭ ɨɛʁɚɜʂɟɧɢ ɪɟɡɭɥɬɚɬɢ ɧɟɤɨɥɢɤɨ ɩɪɨɫɩɟɤɬɢɜɧɢɯ ɫɬɭɞɢʁɚ ɨ ɭɥɨɡɢ ɢ ɡɧɚɱɚʁɭKIM-1 ɡɚ ɞɢʁɚɝɧɨɡɭ ɫɄȻ. ɉɪɜɚ ɬɚɤɜɚ ɫɬɭɞɢʁɚ Han ɢ ɫɚɪ. ɨɛʁɚɜʂɟɧɚ ʁɟ 2005. ɝɨɞɢɧɟ. ɋɬɭɞɢʁɚ ʁɟ ɫɩɪɨɜɟɞɟɧɚ ɧɚ 42 ɩɚɰɢʁɟɧɬɚ ɫɚ ɩɪɢɦɚɪɧɢɦ ɬɭɦɨɪɨɦ ɛɭɛɪɟɝɚ ɤɨɞ ɤɨʁɢɯ ʁɟ ɧɚɤɨɧ ɨɩɟɪɚɬɢɜɧɨɝ ɥɟɱɟʃɚ ɩɚɬɨɯɢɫɬɨɥɨɲɤɨɦ ɚɧɚɥɢɡɨɦ ɩɨɬɜɪђɟɧɚ ɞɢʁɚɝɧɨɡɚ ɤɚɪɰɢɧɨɦɚ ɛɭɛɪɟɝɚ. ɂɫɬɨɜɪɟɦɟɧɨ ʁɟ ɤɨɞ ɫɜɢɯ ɛɨɥɟɫɧɢɤɚ ɭɡɟɬ ɭɡɨɪɚɤ ɭɪɢɧɚ ɡɚ ɨɞɪɟђɢɜɚʃɟ ɭɪɢɧɚɪɧɟ ɤɨɧɰɟɧɬɪɚɰɢʁɟ KIM-1 ɢ ɬɨ ɩɪɟ ɨɩɟɪɚɰɢʁɟ, ɩɨɫɬɨɩɟɪɚɬɢɜɧɨ ɢ 4 ɞɨ 6 ɧɟɞɟʂɚ ɧɚɤɨɧ ɨɩɟɪɚɬɢɜɧɨɝ ɥɟɱɟʃɚ. Ʉɨɧɬɪɨɥɧɭ ɝɪɭɩɭ ɱɢɧɢɥɨ ʁɟ 30 ɡɞɪɚɜɢɯ ɢɫɩɢɬɚɧɢɤɚ ɫɚ ɧɨɪɦɚɥɧɨɦ ɛɭɛɪɟɠɧɨɦ ɮɭɧɤɰɢʁɨɦ ɢ ɛɟɡ ɪɚɧɢʁɢɯ ɛɭɛɪɟɠɧɢɯ ɛɨɥɟɫɬɢ. ɂɡɜɪɲɟɧɨ ʁɟ ɢɦɭɧɨɯɢɫɬɨɯɟɦɢʁɫɤɨ ɛɨʁɟʃɟ ɧɚ ɩɪɢɫɭɫɬɜɨ ɯɭɦɚɧɨɝ KIM-1 (hKIM-1) ɤɨɞ 40 ɭɡɨɪɚɤɚ ɬɤɢɜɚ ɛɭɛɪɟɠɧɨɝ ɤɚɪɰɢɧɨɦɚ, ɞɨɤ ʁɟ ɤɨɧɬɪɨɥɧɭ ɝɪɭɩɭ ɱɢɧɢɥɨ 484 ɬɤɢɜɧɚ ɭɡɨɪɤɚ ɧɟɪɟɧɚɥɧɢɯ ɬɭɦɨɪɚ. ȿɤɫɩɪɟɫɢʁɚ KIM-1 ʁɟ ɞɨɤɚɡɚɧɚ ɭ 91% ɫɥɭɱɚʁɟɜɚ ɫɄȻ. ɂ ɭ ɫɥɭɱɚʁɟɜɢɦɚ ɤɚɞɚ ɬɭɦɨɪɫɤɟ ʄɟɥɢʁɟ ɧɢɫɭ ɩɨɤɚɡɢɜɚɥɟ ɩɨɡɢɬɢɜɧɨɫɬ ɧɚ KIM-1 ɚɧɬɢɬɟɥɨ, ɫɭɫɟɞɧɟ ɬɭɛɭɥɫɤɟ ʄɟɥɢʁɟ ɫɭ ɨɛɢɱɧɨ ɛɢɥɟ ɩɨɡɢɬɢɜɧɟ. ɇɚђɟɧɚ ʁɟ ɟɤɫɩɪɟɫɢʁɚ KIM-1 ɭ ɦɟɬɚɫɬɚɡɢ ɬɭɦɨɪɚ ɭ ɥɢɦɮɧɨɦ ɱɜɨɪɭ ɤɨɞ 2 ɩɚɰɢʁɟɧɬɚ. ɉɪɢɫɭɫɬɜɨ KIM-1 ɧɢʁɟ ɞɨɤɚɡɚɧɨ ɭ ɝɥɨɦɟɪɭɥɢɦɚ, ɤɚɨ ɧɢ ɭ ɧɟɤɚɧɰɟɪɫɤɨɦ ɬɭɛɭɥɨɢɧɬɟɪɫɬɢɰɢʁɫɤɨɦ ɬɤɢɜɭ. ɍ ɤɨɧɬɪɨɥɧɨʁ ɝɪɭɩɢ ɧɟɪɟɧɚɥɧɢɯ ɬɭɦɨɪɚ, ɩɨɡɢɬɢɜɧɨɫɬ ɧɚ KIM-1 ɧɚђɟɧɚ ʁɟ ɫɚɦɨ ɤɨɞ ʁɟɞɧɨɝ ɨɞ ɞɜɚ ɭɡɨɪɤɚ ɯɟɩɚɬɨɰɟɥɭɥɚɪɧɨɝ ɤɚɪɰɢɧɨɦɚ. ELISA ɦɟɬɨɞɨɦ ɨɞɪɟђɟɧɚ ʁɟ ɤɨɧɰɟɧɬɪɚɰɢʁɚ KIM-1 ɭ ɭɪɢɧɭ ɢ ɞɨɤɚɡɚɧɚ ɫɬɚɬɢɫɬɢɱɤɢ ɡɧɚɱɚʁɧɨ ɜɢɲɚ ɤɨɧɰɟɧɬɪɚɰɢʁɚ ɤɨɞ ɩɚɰɢʁɟɧɚɬɚ ɫɚɫɄȻ ɭ ɩɨɪɟђɟʃɭ ɫɚ ɨɫɬɚɥɢɦ ɬɢɩɨɜɢɦɚ ɪɟɧɚɥɧɨɝ ɤɚɪɰɢɧɨɦɚ, ɤɚɨ ɢ ɭ ɤɨɧɬɪɨɥɧɨʁ ɝɪɭɩɢ ɡɞɪɚɜɢɯ. ɉɨɫɬɨʁɚɥɚ ʁɟ ʁɚɤɚ ɩɨɡɢɬɢɜɧɚ ɤɨɪɟɥɚɰɢʁɚ ɢɡɦɟђɭ ɜɟɥɢɱɢɧɟ ɬɭɦɨɪɚ ɢ ɤɨɧɰɟɧɬɪɚɰɢʁɟ uKIM-1145. Morrissey ɢ ɫɚɪ.ɫɭ 2011. ɨɛʁɚɜɢɥɢ ɪɟɡɭɥɬɚɬɟ ɩɪɨɫɩɟɤɬɢɜɧɟ ɫɬɭɞɢʁɟ ɤɨʁɚ ʁɟ ɢɫɩɢɬɢɜɚɥɚ ɫɟɧɡɢɬɢɜɧɨɫɬ ɢ ɫɩɟɰɢɮɢɱɧɨɫɬ 2 ɭɪɢɧɚɪɧɚ ɛɢɨɦɚɪɤɟɪɚɡɚ ɞɢʁɚɝɧɨɡɭ ɤɚɪɰɢɧɨɦɚ ɛɭɛɪɟɝɚ, uKIM-1 ɢ ɡɚ ɠɟɥɚɬɢɧɚɡɭ ɧɟɭɬɪɨɮɢɥɚ ɜɟɡɚɧ ɥɢɩɨɤɚɥɢɧ (uNGAL). ɂɫɩɢɬɢɜɚʃɟ ʁɟ ɫɩɪɨɜɟɞɟɧɨ ɧɚ 54 ɩɚɰɢʁɟɧɬɚ ɫɚ ɯɢɫɬɨɥɨɲɤɢ ɞɨɤɚɡɚɧɢɦ ɫɄȻ ɢ 13 ɩɚɰɢʁɟɧɚɬɚ ɫɚ ɩɄȻ. ɍɡɨɪɰɢ ɭɪɢɧɚ ɫɭ ɭɡɟɬɢ ɩɪɟ ɧɟɮɪɟɤɬɨɦɢʁɟ ɢ ɩɪɢ ɤɨɧɬɪɨɥɧɨɦ ɩɪɟɝɥɟɞɭ 1-3 ɦɟɫɟɰɚ ɧɚɤɨɧ ɨɩɟɪɚɬɢɜɧɨɝ ɥɟɱɟʃɚ. Ʉɨɧɬɪɨɥɧɭ ɝɪɭɩɭ ɱɢɧɢɥɨ ʁɟ 55 ɩɚɰɢʁɟɧɚɬɚ ɤɨɞ ɤɨʁɢɯ ɫɭ ɫɩɪɨɜɟɞɟɧɟ ɨɪɬɨɩɟɞɫɤɟ ɨɩɟɪɚɰɢʁɟ, ɚ ɭɡɨɪɰɢ ɭɪɢɧɚ ɫɭ ɭɡɟɬɢ ɩɪɟɨɩɟɪɚɬɢɜɧɨ ɢ 1-3 ɦɟɫɟɰɚ ɧɚɤɨɧ ɨɩɟɪɚɬɢɜɧɨɝ ɥɟɱɟʃɚ. Ʉɨɧɰɟɧɬɪɚɰɢʁɚ uNGAL-ɚ ɤɨɞ 67 ɩɚɰɢʁɟɧɚɬɚ ɫɚ ɤɚɪɰɢɧɨɦɨɦ ɛɭɛɪɟɝɚ ɛɢɥɚ ʁɟ ɫɢɝɧɢɮɢɤɚɧɬɧɨ ɜɢɲɚ ɭ ɩɨɪɟђɟʃɭ ɫɚ ɤɨɧɬɪɨɥɧɨɦ ɝɪɭɩɨɦ. ɇɢʁɟ ɧɚђɟɧɚ ɫɢɝɧɢɮɢɤɚɧɬɧɚ ɤɨɪɟɥɚɰɢʁɚ ɢɡɦɟђɭ ɤɨɧɰɟɧɬɪɚɰɢʁɟ uNGAL-ɚ ɢ ɜɟɥɢɱɢɧɟ ɬɭɦɨɪɚ. Ɂɚ ɪɚɡɥɢɤɭ ɨɞ NGAL-ɚ, ɩɨɫɬɨʁɚɥɚ ʁɟ ɩɨɡɢɬɢɜɧɚ ɤɨɪɟɥɚɰɢʁɚ ɢɡɦɟђɭ ɤɨɧɰɟɧɬɪɚɰɢʁɟ uKIM-1 ɢ ɫɬɚɞɢʁɭɦɚ ɛɨɥɟɫɬɢ ɢ ɜɟɥɢɱɢɧɟ ɬɭɦɨɪɚ, ɤɚɨ ɢ ɫɢɝɧɢɮɢɤɚɧɬɧɨ ɜɢɲɚ ɤɨɧɰɟɧɬɪɚɰɢʁɚ ɨɜɨɝ ɛɢɨɦɚɪɤɟɪɚ ɭ ɩɨɪɟђɟʃɭ ɫɚ ɤɨɧɬɪɨɥɧɨɦ ɝɪɭɩɨɦ. ɍȼɈȾ 19 ɋɟɧɡɢɬɢɜɧɨɫɬ ɢ ɫɩɟɰɢɮɢɱɧɨɫɬ uKIM-1 ɢɡɧɨɫɢɥɚ ʁɟ 0,75 ɢɡɪɚɠɟɧɨ ɩɪɟɤɨ ROCɤɪɢɜɟ.Ɂɚɤʂɭɱɟɧɨ ʁɟ ɞɚ ɫɭ ɤɨɧɰɟɧɬɪɚɰɢʁɟ uKIM-1 ɚɥɢ ɧɟ ɢ uNGAL, ɛɢɥɟ ɫɬɚɬɢɫɬɢɱɤɢ ɡɧɚɱɚʁɧɨ ɜɢɲɟ ɤɨɞ ɩɚɰɢʁɟɧɚɬɚ ɫɚ ɫɄȻ ɢ ɩɄȻ ɭ ɩɨɪɟђɟʃɭ ɫɚ ɤɨɧɬɪɨɥɧɨɦ ɝɪɭɩɨɦ146. ɋɬɭɞɢʁɚ Shalabi ɢ ɫɚɪ. ɨɛɭɯɜɚɬɢɥɚ ʁɟ ɢɫɩɢɬɢɜɚʃɟ 46 ɩɚɰɢʁɟɧɚɬɚ ɤɨɞ ɤɨʁɢɯ ʁɟ ɭɱɢʃɟɧɚ ɧɟɮɪɟɤɬɨɦɢʁɚ, ɨɞ ɤɨʁɢɯ 39 ɫɚ ɩɪɢɦɚɪɧɢɦ ɬɭɦɨɪɨɦ ɛɭɛɪɟɝɚ ɢ 9 ɫɚ ɚɮɭɧɤɰɢɨɧɚɥɧɢɦ ɛɭɛɪɟɝɨɦ. Ʉɨɞ ɫɜɢɯ ɩɚɰɢʁɟɧɚɬɚ ɩɪɟ ɨɩɟɪɚɰɢʁɟ ʁɟ ɭɡɟɬ ɭɡɨɪɚɤ ɭɪɢɧɚ ɡɚ ɨɞɪɟђɢɜɚʃɟ uKIM-1 ɢ uNGAL. ɇɚɤɨɧ ɨɩɟɪɚɬɢɜɧɨɝ ɥɟɱɟʃɚ ɩɚɰɢʁɟɧɬɢ ɫɭ ɫɜɪɫɬɚɧɢ ɭ ɝɪɭɩɭ ɫɚ ɯɢɫɬɨɥɨɲɤɢ ɞɨɤɚɡɚɧɢɦ ɤɚɪɰɢɧɨɦɨɦ ɛɭɛɪɟɝɚ (31 ɢɫɩɢɬɚɧɢɤ), ɞɨɤ ɫɭ ɤɨɧɬɪɨɥɧɭ ɝɪɭɩɭ ɱɢɧɢɥɢ ɩɚɰɢʁɟɧɬɢ ɫɚ ɛɟɧɢɝɧɢɦ ɬɭɦɨɪɫɤɢɦ ɥɟɡɢʁɚɦɚ ɢ ɚɮɭɧɤɰɢɨɧɚɥɧɢɦ ɛɭɛɪɟɝɨɦ (15 ɢɫɩɢɬɚɧɢɤɚ). ɉɚɰɢʁɟɧɬɢ ɫɚ ɤɚɪɰɢɧɨɦɨɦ ɛɭɛɪɟɝɚ ɫɭ ɩɨɞɟʂɟɧɢ ɭ 3 ɝɪɭɩɟ ɩɪɟɦɚ ɯɢɫɬɨɥɨɲɤɨɦ ɬɢɩɭ:ɫɄȻ-14 ɩɚɰɢʁɟɧɚɬɚ, ɯɄȻ-3 ɢ ɩɄȻ-4 ɩɚɰɢʁɟɧɬɚ. ɐɢʂ ɫɬɭɞɢʁɟ ʁɟ ɛɢɨ ɞɚ ɫɟ ɢɫɩɢɬɚ ɩɨɜɟɡɚɧɨɫɬ ɤɨɧɰɟɧɬɪɚɰɢʁɚ uKIM-1 ɢ uNGAL ɤɚɨ ɛɢɨɦɚɪɤɟɪɚ ɡɚ ɨɞɪɟђɢɜɚʃɟ ɯɢɫɬɨɥɨɲɤɢɯ ɤɚɪɚɤɬɟɪɢɫɬɢɤɚ ɪɚɞɢɨɝɪɚɮɫɤɢ ɨɬɤɪɢɜɟɧɢɯ ɬɭɦɨɪɫɤɢɯ ɩɪɨɦɟɧɚ. Ʉɨɧɰɟɧɬɪɚɰɢʁɚ uNGAL ɭ ɝɪɭɩɢ ɫɚ ɤɚɪɰɢɧɨɦɨɦ ɛɭɛɪɟɝɚ ɧɢʁɟ ɛɢɥɚ ɫɢɝɧɢɮɢɤɚɧɬɧɨ ɪɚɡɥɢɱɢɬɚ ɭ ɩɨɪɟђɟʃɭ ɫɚ ɤɨɧɬɪɨɥɧɨɦ, ɩɪɢ ɱɟɦɭ ʁɟ ɧɚʁɜɢɲɚ ɤɨɧɰɟɧɬɪɚɰɢʁɚ ɧɚђɟɧɚ ɭ ɝɪɭɩɢ ɫɚ ɩɚɩɢɥɚɪɧɢɦ ɤɚɪɰɢɧɨɦɨɦ. Ʉɨɧɰɟɧɬɪɚɰɢʁɚ uKIM-1, ɬɚɤɨђɟ ɫɟ ɧɢʁɟ ɡɧɚɱɚʁɧɨ ɪɚɡɥɢɤɨɜɚɥɚ ɢɡɦɟђɭ ɞɜɟ ɝɪɭɩɟ. ɇɚʁɜɢɲɚ ɤɨɧɰɟɧɬɪɚɰɢʁɚ uKIM-1 ɞɨɛɢʁɟɧɚ ʁɟ ɭ ɝɪɭɩɢ ɩɚɰɢʁɟɧɚɬɚ ɫɚ ɫɄȻ ɭ ɩɨɪɟђɟʃɭ ɫɚ ɨɫɬɚɥɢɦ ɯɢɫɬɨɥɨɲɤɢɦ ɩɨɞɬɢɩɨɜɢɦɚ, ɲɬɨ ʁɟ ɞɨɤɚɡɚɧɨ ɢ ɭ ɫɬɭɞɢʁɚɦɚ Han ɢ Morrissey. Ɉɜɚ ɫɬɭɞɢʁɚ ɧɢʁɟ ɩɨɤɚɡɚɥɚ ɤɨɪɟɥɚɰɢʁɭ ɤɨɧɰɟɧɬɪɚɰɢʁɟ uKIM-1 ɫɚ ɜɟɥɢɱɢɧɨɦ ɬɭɦɨɪɚ ɢ ɯɢɫɬɨɥɨɲɤɢɦ ɝɪɚɞɭɫɨɦ, ɲɬɨ ʁɟ ɨɛʁɚɲʃɟɧɨ ɱɢʃɟɧɢɰɨɦ ɞɚ ʁɟ ɭ ɨɜɨʁ ɫɬɭɞɢʁɢ ɜɟʄɢɧɚ ɩɚɰɢʁɟɧɚɬɚ ɢɦɚɥɚ ɦɚʃɟ ɬɭɦɨɪɫɤɟ ɩɪɨɦɟɧɟ (4.57± 0.37cm)147. Zhang ɢ ɫɚɪ. ɫɭ ɭ ɫɜɨʁɨʁ ɫɬɭɞɢʁɢ ɚɧɚɥɢɡɢɪɚɥɢ 19 ɩɚɰɢʁɟɧɚɬɚ, ɤɨʁɟ ɫɭ ɩɪɟɦɚ ɢɦɭɧɨɯɢɫɬɨɯɟɦɢʁɫɤɨʁ ɩɨɡɢɬɢɜɧɨɫɬɢ ɧɚ KIM-1 ɩɨɞɟɥɢɥɢ ɭ ɞɜɟ ɝɪɭɩɟ: KIM-1 ɩɨɡɢɬɢɜɧɚ ɝɪɭɩɚ ɭ ɤɨʁɨʁ ʁɟ ɛɢɥɨ 12 ɩɚɰɢʁɟɧɚɬɚ (8 ɫɚ ɞɢʁɚɝɧɨɡɨɦ ɫɄȻ ɢ 4 ɫɚ ɞɢʁɚɝɧɨɡɨɦ ɩɄȻ) ɢ KIM-1 ɧɟɝɚɬɢɜɧɚ ɝɪɭɩɚ ɭ ɤɨʁɨʁ ʁɟ ɛɢɥɨ 7 ɩɚɰɢʁɟɧɚɬɚ (2 ɫɚ ɞɢʁɚɝɧɨɡɨɦ ɯɄȻ ɢ 5 ɫɚ ɛɟɧɢɝɧɢɦ ɪɟɧɚɥɧɢɦ ɥɟɡɢʁɚɦɚ). ɉɨɪɟђɟʃɟɦ ɨɜɟ ɞɜɟ ɝɪɭɩɟ ɢɫɩɢɬɚɧɢɤɚ ɞɨɛɢʁɟɧɨ ʁɟ ɡɧɚɱɚʁɧɨ ɫɧɢɠɟʃɟ uKIM1 ɧɚɤɨɧ ɨɩɟɪɚɰɢʁɟ ɭ ɩɨɪɟђɟʃɭ ɫɚ ɩɪɟɨɩɟɪɚɬɢɜɧɢɦ ɜɪɟɞɧɨɫɬɢɦɚ ɫɚɦɨ ɭ KIM-1 ɩɨɡɢɬɢɜɧɨʁ ɝɪɭɩɢ. Ɋɟɡɭɥɬɚɬ ɨɜɟ ɫɬɭɞɢʁɟ ʁɟ ɩɨɤɚɡɚɨ ɞɚ uKIM-1 ɦɨɠɟ ɛɢɬɢ ɞɨɞɚɬɧɢ ɦɚɪɤɟɪ ɡɚ ɞɢʁɚɝɧɨɡɭ ɫɄȻ, ɱɢɦɟ ɫɟ ɫɦɚʃɭʁɟ ɢɡɥɚɝɚʃɟ ɨɜɢɯ ɩɚɰɢʁɟɧɚɬɚ ɡɪɚɱɟʃɭ ɩɪɢɥɢɤɨɦ ɩɨɧɚɜʂɚɧɢɯ ɪɚɞɢɨɥɨɲɤɢɯ ɢɫɩɢɬɢɜɚʃɚ, ɫɦɚʃɭʁɟ ɩɫɢɯɨɥɨɲɤɢ ɫɬɪɟɫ ɢ ɩɪɟɜɟɧɢɪɚ ɤɚɫɧɚ ɞɟɬɟɤɰɢʁɚ ɩɪɨɝɪɟɫɢʁɟ ɛɨɥɟɫɬɢ148. ɇɚ ɨɫɧɨɜɭ ɪɟɡɭɥɚɬɚɬɚ ɧɚɜɟɞɟɧɢɯ ɫɬɭɞɢʁɚ, ɦɨɠɟ ɫɟ ɡɚɤʂɭɱɢɬɢ ɞɚ ɨɞɪɟђɢɜɚʃɟ ɭɪɢɧɚɪɧɟ ɤɨɧɰɟɧɬɪɚɰɢʁɟ KIM-1 ɩɪɟɞɫɬɚɜʂɚ ɫɟɧɡɢɬɢɜɚɧ ɦɚɪɤɟɪ ɡɚ ɞɢʁɚɝɧɨɡɭ ɫɄȻ, ɩɪɢ ɱɟɦɭ ʁɟ ʃɟɝɨɜ ɡɧɚɱɚʁ ɩɨɤɚɡɚɧ ɭ ɦɚʃɟɦ ɛɪɨʁɭ ɩɪɨɫɩɟɤɬɢɜɧɢɯ ɫɬɭɞɢʁɚ ɢ ɧɚ ɪɟɥɚɬɢɜɧɨ ɦɚɥɨɦ ɛɪɨʁɭ ɢɫɩɢɬɚɧɢɤɚ. ɍȼɈȾ 20 1.7.2. Ⱥɤɜɚɩɨɪɢɧ 1 (AQP-1) Ⱥɤɜɚɩɨɪɢɧɢ (AQP) ɫɭ ɮɚɦɢɥɢʁɚ ɦɚɥɢɯ ɦɟɦɛɪɚɧɫɤɢɯ ɬɪɚɧɫɩɨɪɬɧɢɯ ɩɪɨɬɟɢɧɚ, ɬɟɠɢɧɟ ɩɪɢɛɥɢɠɧɨ 30 kDa/ɦɨɧɨɦɟɪɭ, ɤɨʁɢ ɫɟ ɧɚɥɚɡɟ ɧɚ ʄɟɥɢʁɫɤɢɦ ɦɟɦɛɪɚɧɚɦɚ ɭ ɮɨɪɦɢ ɬɟɬɪɚɦɟɪɚ ɢ ɢɦɚʁɭ ɭɥɨɝɭ ɩɨɪɚ ɫɟɥɟɤɬɢɜɧɢɯ ɡɚ ɜɨɞɭ, ɜɪɲɟʄɢ ɨɫɦɨɬɫɤɢ ɬɪɚɧɫɩɨɪɬ ɜɨɞɟ ɤɪɨɡ ɦɟɦɛɪɚɧɭ. Ⱦɨ ɫɚɞɚ ʁɟ ɨɬɤɪɢɜɟɧɨ 13 ɬɢɩɨɜɚ ɚɤɜɚɩɨɪɢɧɚɤɨʁɢ ɫɭ ɫɧɚɠɧɨ ɟɤɫɩɪɢɦɢɪɚɧɢ ɢ ɮɭɧɤɰɢɨɧɚɥɧɨ ɡɧɚɱɚʁɧɢ ɭ ɛɭɛɪɟɝɭ, ɰɟɧɬɪɚɥɧɨɦ ɧɟɪɜɧɨɦ ɫɢɫɬɟɦɭ, ɨɤɭ, ɤɨɠɢ ɢ ɟɝɡɨɤɪɢɧɢɦ ɠɥɟɡɞɚɦɚ149. ɍ ɛɭɛɪɟɝɭ ɫɟ ɟɤɫɩɪɢɦɢɪɚ 7 ɬɢɩɨɜɚ ɚɤɜɚɩɨɪɢɧɚ: AQP-1, AQP-2, AQP-3, AQP-4, AQP-6, AQP-7 ɢ AQP-11. AQP-1 ɫɟ ɟɤɫɩɪɢɦɢɪɚ ɧɚ ʄɟɥɢʁɚɦɚ ɩɪɨɤɫɢɦɚɥɧɢɯ ɬɭɛɭɥɚ, ɬɚɧɤɨɦ ɞɟɫɰɟɞɟɧɬɧɨɦ ɤɪɚɤɭ ɏɟɧɥɟɨɜɟ ɩɟɬʂɟ ɢ ɟɧɞɨɬɟɥɧɢɦ ʄɟɥɢʁɚɦɚ vasa rectɚ, AQP-2 ɧɚ ɚɩɢɤɚɥɧɨʁ ɦɟɦɛɪɚɧɢ ɫɚɛɢɪɧɢɯ ɤɚɧɚɥɢʄɚ, ɞɨɤ ɫɟ AQP-3 ɢ AQP-4 ɟɤɫɩɪɢɦɢɪɚʁɭ ɧɚ ɛɚɡɨɥɚɬɟɪɚɥɧɨʁ ɦɟɦɛɪɚɧɢ ɟɩɢɬɟɥɧɢɯ ʄɟɥɢʁɚ ɫɚɛɢɪɧɢɯ ɤɚɧɚɥɢʄɚ. ɇɚɜɟɞɟɧɢ ɬɢɩɨɜɢ ɚɤɜɚɩɨɪɢɧɚ ɢɦɚʁɭ ɰɟɧɬɪɚɥɧɭ ɭɥɨɝɭ ɭ ɛɭɛɪɟɠɧɨʁ ɪɟɝɭɥɚɰɢʁɢ ɟɤɫɤɪɟɰɢʁɟ ɫɨɥɢ ɢ ɜɨɞɟ ɩɭɬɟɦ ɭɪɢɧɚ. Ⱦɟɮɢɰɢʁɟɧɰɢʁɚ ɮɭɧɤɰɢʁɟ AQP-1 ɢɦɚ ɡɚ ɩɨɫɥɟɞɢɰɭ ɨɲɬɟʄɟɧɭ ɚɩɫɨɪɩɰɢʁɭ ɢɡɨɨɫɦɨɥɚɪɧɟ ɬɟɱɧɨɫɬɢ ɢɡ ɩɪɨɤɫɢɦɚɥɧɨɝ ɬɭɛɭɥɚ, ɞɨɤ ɞɟɮɢɰɢʁɟɧɰɢʁɚ AQP-2, AQP-3 ɢ AQP-4 ɞɨɜɨɞɢ ɞɨ ɨɲɟɬɟʄɟʃɚ ɜɚɡɨɩɪɟɫɢɧɨɦ ɩɨɫɪɟɞɨɜɚɧɟ ɪɟɝɭɥɚɰɢʁɟ ɩɪɨɩɭɫɬʂɢɜɨɫɬɢ ɜɨɞɟ ɭ ɫɚɛɢɪɧɢɦ ɤɚɧɚɥɢʄɢɦɚ. ɋɦɚʃɟɧɚ ɟɤɫɩɪɟɫɢʁɚ AQP-2 ɢɦɚ ɡɚ ɩɨɫɥɟɞɢɰɭ ɪɚɡɜɨʁ ɫɬɟɱɟɧɟ ɮɨɪɦɟ ɧɟɮɪɨɝɟɧɨɝ ɢɧɫɢɩɢɞɧɨɝ ɞɢʁɚɛɟɬɟɫɚ.AQP-7 ʁɟ ɥɨɤɚɥɢɡɨɜɚɧ ɧɚ ɚɩɢɤɚɥɧɨʁ ɦɟɦɛɪɚɧɢ S3 ɫɟɝɦɟɧɬɚ ɩɪɨɤɫɢɦɚɥɧɢɯ ɬɭɛɭɥɚ ɢ ɭɱɟɫɬɜɭʁɟ ɭ ɬɪɚɧɫɩɨɪɬɭ ɜɨɞɟ ɢ ɝɥɢɰɟɪɨɥɚ. AQP-6 ɢ AQP-11 ɫɟ ɧɚɥɚɡɟ ɢɧɬɪɚɰɟɥɭɥɚɪɧɨ, ɩɪɢ ɱɟɦɭ AQP-6 ɢɦɚ ɩɪɢɦɚɪɧɭ ɭɥɨɝɭ ɭ ɚɧʁɨɧɫɤɨɦ ɬɪɚɧɫɩɨɪɬɭ, ɞɨɤ AQP- 11 ɭɱɟɫɬɜɭʁɟ ɭ ɬɪɚɧɫɩɨɪɬɭ ɜɨɞɟ. ɇɟɞɨɫɬɚɬɚɤ AQP-11 ɩɨɜɟɡɚɧ ʁɟ ɫɚ ɪɚɡɜɨʁɟɦ ɩɨɥɢɰɢɫɬɢɱɧɟ ɛɨɥɟɫɬɢ ɛɭɛɪɟɝɚ150,151,152. Ɉɬɤɪɢʄɟ ɨ ɭɱɟɲʄɭ AQP ɭ ɩɪɨɰɟɫɭ ɬɭɦɨɪɫɤɟ ʄɟɥɢʁɫɤɟ ɩɪɨɥɢɮɟɪɚɰɢʁɟ ɢ ɦɢɝɪɚɰɢʁɟ, ɭɤɚɡɭʁɟ ɞɚ ɚɤɜɚɩɨɪɢɧɢ ɢɦɚʁɭ ɡɧɚɱɚʁɧɭ ɭɥɨɝɭ ɭ ɛɢɨɥɨɝɢʁɢ ɬɭɦɨɪɚ. ɉɨɫɬɨʁɟ ɞɜɚ ɦɟɯɚɧɢɡɦɚ ɤɨʁɢɦɚ ɫɟ ɦɨɠɟ ɨɛʁɚɫɧɢɬɢ ɧɚɱɢɧ ɧɚ ɤɨʁɢ AQP ɭɛɪɡɚɜɚʁɭ ʄɟɥɢʁɫɤɭ ɦɢɝɪɚɰɢʁɭ. ɉɪɟɦɚ ɩɪɜɨʁ ɬɟɨɪɢʁɢ, ɚɤɜɚɩɨɪɢɧɢ ɨɦɨɝɭʄɚɜɚʁɭ ɪɚɩɢɞɧɢ ɩɪɨɥɚɡ ɜɨɞɟ ɤɪɨɡ ɩɥɚɡɦɚ ɦɟɦɛɪɚɧɭ. Ɉɜɚʁ ɪɚɩɢɞɧɢ ɬɪɚɧɫɦɟɦɛɪɚɧɫɤɢ ɬɪɚɧɫɩɨɪɬ ɩɨɫɥɟɞɢɰɚ ʁɟ ɩɪɨɦɟɧɟ ɭ ɨɫɦɨɥɚɥɧɨɫɬɢ ɧɚɫɬɚɥɟ ɡɛɨɝ ɢɧɮɥɭɤɫɚ ʁɨɧɚ ɢ ɞɟɩɨɥɢɦɟɪɢɡɚɰɢʁɟ ɚɤɬɢɧɚ. ɉɪɟɦɚ ɞɪɭɝɨʁ ɬɟɨɪɢʁɢ, ɞɨɥɚɡɢ ɞɨ ɩɪɨɬɪɭɡɢʁɟ ɦɟɦɛɪɚɧɟ ɢ ɫɬɜɚɪɚʃɚ ɬɡɜ. ɥɚɦɟɥɢɩɨɞɢɚ ɤɚɨ ɩɨɫɥɟɞɢɰɚ ɩɨɜɟʄɚɧɨɝ ɯɢɞɪɨɫɬɚɬɫɤɨɝ ɩɪɢɬɢɫɤɚ ɡɛɨɝ ɪɚɩɢɞɧɨɝ ɬɪɚɧɫɦɟɦɛɪɚɧɫɤɨɝ ɭɥɚɫɤɚ ɜɨɞɟ. ɍɛɪɡɚɧɨ ʄɟɥɢʁɫɤɨ ɤɪɟɬɚʃɟ ɩɨɫɥɟɞɢɰɚ ʁɟ ɫɬɜɚɪɚʃɚ ɨɜɢɯ ɢɪɟɝɭɥɚɪɧɨ ɨɛɥɢɤɨɜɚɧɢɯ ɟɤɫɬɪɚɰɟɥɭɥɚɪɧɢɯ ɧɚɫɬɚɜɚɤɚ. ȿɤɫɩɪɟɫɢʁɚ AQP ɞɨɜɨɞɢ ɞɨ ɩɨɜɟʄɚʃɚ ɛɪɨʁɚ ɢ ɨɛɥɢɤɚ ɥɚɦɟɥɢɩɨɞɢɚ153. Ⱥɤɜɚɩɨɪɢɧ 1(AQP-1) ʁɟ ɨɬɤɪɢɜɟɧ 1985. ɝɨɞɢɧɟ ɧɚ ɦɟɦɛɪɚɧɢ ɟɪɢɬɪɨɰɢɬɚ ɨɞ ɫɬɪɚɧɟ Beng ɢ ɫɚɪ. ɢ ɩɪɟɞɫɬɚɜʂɚ ɩɪɜɢ ɢɧɞɟɧɬɢɮɢɤɨɜɚɧɢ ɦɟɦɛɪɚɧɫɤɢ ɬɪɚɧɫɩɨɪɬɧɢ ɩɪɨɬɟɢɧ ɡɚ ɜɨɞɭ. Ƚɟɧ ɡɚ AQP-1 ɫɟ ɧɚɥɚɡɢ ɧɚ ɤɪɚɬɤɨɦ ɤɪɚɤɭ ɯɪɨɦɨɡɨɦɚ 7 (7p14). AQP-1 ʁɟ ɥɨɤɚɥɢɡɨɜɚɧ ɧɚ ɚɩɢɤɚɥɧɨʁ ɢ ɛɚɡɨɥɚɬɟɪɚɥɧɨʁ ɦɟɦɛɪɚɧɢ ɩɪɨɤɫɢɦɚɥɧɨɝ ɬɭɛɭɥɚ ɢ ɬɚɧɤɨɦ ɧɢɫɯɨɞɧɨɦ ɤɪɚɤɭ ɏɟɧɥɟɨɜɟ ɩɟɬʂɟ ɢ ɨɞɝɨɜɨɪɚɧ ʁɟ ɡɚ ɪɟɚɩɫɨɪɩɰɢʁɭ 75% ɜɨɞɟ ɢɡ ɝɥɨɦɟɪɭɥɚɪɧɨɝ ɮɢɥɬɪɚɬɚ, ɱɢɦɟ ɩɪɟɞɫɬɚɜʂɚ ɝɥɚɜɧɢ ɱɢɧɢɥɚɰ ɭ ɦɟɯɚɧɢɡɦɭ ɤɨɧɰɟɧɬɪɚɰɢʁɟ ɭɪɢɧɚ. ȿɤɫɩɪɟɫɢʁɚ AQP-1 ɧɚ ɝɥɨɦɟɪɭɥɚɪɧɢɦ ɟɧɞɨɬɟɥɧɢɦ ʄɟɥɢʁɚɦɚ ʁɟ ɡɧɚɱɚʁɧɨ ɩɨɜɟʄɚɧɚ ɭ ɦɧɨɝɢɦ ɝɥɨɦɟɪɭɥɫɤɢɦ ɍȼɈȾ 21 ɛɨɥɟɫɬɢɦɚ ɤɚɨ ɲɬɨ ɫɭ:ɛɨɥɟɫɬ ɦɢɧɢɦɚɥɧɢɯ ɩɪɨɦɟɧɚ, ɯɪɨɧɢɱɧɢ ɦɟɡɚɧɝɢɨɩɪɨɥɢɮɟɪɚɬɢɜɧɢ ɝɥɨɦɟɪɭɥɨɧɟɮɪɢɬɢɫ, ɪɚɩɢɞɧɨ-ɩɪɨɝɪɟɫɢɜɧɢ ɝɥɨɦɟɪɭɥɨɧɟɮɪɢɬɢɫ, ɥɭɩɭɫ ɧɟɮɪɢɬɢɫ, ɬɭɛɭɥɨɢɧɬɟɪɫɬɢɰɢʁɫɤɢ ɧɟɮɪɢɬɢɫ ɢ ɧɟɮɪɨɫɤɥɟɪɨɡɚ154. ɉɚɬɨɯɢɫɬɨɥɨɲɤɚ ɫɬɭɞɢʁɚ Huang ɢ ɫɚɪ. ɩɨɤɚɡɚɥɚ ʁɟ ɜɢɫɨɤɭ ɟɤɫɩɪɟɫɢʁɭ AQP-1 ɤɨɞ ɫɄȻ ɢ ɩɄȻ, ɨɛɚ ɩɨɪɟɤɥɚ ɩɪɨɤɫɢɦɚɥɧɨɝ ɬɭɛɭɥɚ. ɇɚђɟɧɚ ʁɟ ɡɧɚɱɚʁɧɨ ɜɟʄɚ ɟɤɫɩɪɟɫɢʁɚ AQP-1 ɤɨɞ ɩɚɰɢʁɟɧɚɬɚ ɫɚ ɬɭɦɨɪɢɦɚ ɦɚʃɢɯ ɞɢɦɟɧɡɢʁɚ, ɧɢɠɟɝ ɫɬɚɞɢʁɭɦɚ ɛɨɥɟɫɬɢ ɢ ɯɢɫɬɨɥɨɲɤɨɝ ɝɪɚɞɭɫɚ, ɛɟɡ ɦɢɤɪɨɜɚɫɤɭɥɚɪɧɟ ɢɧɜɚɡɢʁɟ ɬɭɦɨɪɫɤɢɦ ʄɟɥɢʁɚɦɚ. Ɉɜɢ ɩɚɰɢʁɟɧɬɢ ɫɭ ɢɦɚɥɢ ɡɧɚɱɚʁɧɨ ɛɨʂɭ ɫɬɨɩɭ ɩɪɟɠɢɜʂɚɜɚʃɚ ɭ ɩɨɪɟђɟʃɭ ɫɚ ɨɧɢɦ ɤɨʁɢ ɫɭ ɢɦɚɥɢ ɧɢɫɤɭ ɟɤɫɩɪɟɫɢʁɭ ɨɜɨɝ ɛɢɨɦɚɪɤɟɪɚ. Ɉɜɢ ɩɨɞɚɰɢ ɭɤɚɡɭʁɭ ɞɚ ɛɢ AQP-1 ɤɚɨ ɦɚɪɤɟɪ ɬɭɦɨɪɫɤɟ ɟɤɫɩɪɟɫɢʁɟ, ɦɨɝɚɨ ɛɢɬɢ ɩɨɪɟɞ ɞɢʁɚɝɧɨɫɬɢɱɤɨɝ ɢ ɤɨɪɢɫɬɚɧ ɩɪɨɝɧɨɫɬɢɱɤɢ ɦɚɪɤɟɪ ɤɨɞ ɩɚɰɢʁɟɧɚɬɚ ɫɚ ɫɄȻ155. ɂ ɞɪɭɝɟ ɩɚɬɨɯɢɫɬɨɥɨɲɤɟ ɫɬɭɞɢʁɟ ɫɭ ɩɨɤɚɡɚɥɟ ɨɛɪɧɭɬɭ ɩɨɜɟɡɚɧɨɫɬ ɢɡɦɟђɭ ɬɤɢɜɧɟ ɟɤɫɩɪɟɫɢʁɟ AQP-1 ɢ ɝɪɚɞɭɫɚ ɫɄȻ156,157. ɉɨɞɚɬɚɤ ɞɚ ɫɟ ɚɤɜɚɩɨɪɢɧɢ ɦɨɝɭ ɫɟɤɪɟɬɨɜɚɬɢ ɭ ɭɪɢɧ, ɤɚɨ ɲɬɨ ʁɟ ɫɥɭɱɚʁ ɫɚ AQP-1 ɭ ɫɥɭɱɚʁɭ ɨɲɬɟʄɟʃɚ ɩɪɨɤɫɢɦɚɥɧɨɝ ɬɭɛɭɥɚ, ɚ ɭɡɢɦɚʁɭʄɢ ɭ ɨɛɡɢɪ ɞɚ ɫɄȻ ɧɚɫɬɚʁɟ ɞɟɞɢɮɟɪɟɧɰɢʁɚɰɢʁɨɦ ɟɩɢɬɟɥɧɢɯ ʄɟɥɢʁɚ ɩɪɨɤɫɢɦɚɥɧɨɝ ɬɭɛɭɥɚ, ɩɨɫɥɭɠɢɥɨ ʁɟ ɢɫɬɪɚɠɢɜɚɱɢɦɚ ɞɚ ɢɫɩɢɬɚʁɭ ʃɟɝɨɜ ɡɧɚɱɚʁ ɤɚɨ ɭɪɢɧɚɪɧɨɝ ɛɢɨɦɚɪɤɟɪɚ ɡɚ ɫɄȻ158. Ⱦɨ ɫɚɞɚ ɫɭ ɨɛʁɚɜʂɟɧɢ ɪɟɡɭɥɬɚɬɢ4 ɫɬɭɞɢʁɟ ɤɨʁɟ ɫɭ ɩɨɤɚɡɚɥɟ ɫɬɚɬɢɫɬɢɱɤɢ ɡɧɚɱɚʁɧɨ ɜɢɲɭ ɤɨɧɰɟɧɬɪɚɰɢʁɭ AQP-1 ɭ ɭɪɢɧɭ ɩɚɰɢʁɟɧɚɬɚ ɨɛɨɥɟɥɢɯ ɨɞ ɫɄȻ ɩɪɟ ɨɩɟɪɚɰɢʁɟ ɭ ɩɨɪɟђɟʃɭ ɫɚ ɤɨɧɰɟɧɬɪɚɰɢʁɨɦ ɨɜɨɝ ɛɢɨɦɚɪɤɟɪɚ ɭ ɭɪɢɧɭ ɡɞɪɚɜɢɯ ɢɫɩɢɬɚɧɢɤɚ. ɉɨɫɬɨɩɟɪɚɬɢɜɧɨ ʁɟ ɞɨɲɥɨ ɞɨ ɫɬɚɬɢɫɬɢɱɤɢ ɡɧɚɱɚʁɧɨɝ ɫɧɢɠɟʃɚ ʃɟɝɨɜɟ ɤɨɧɰɟɧɬɪɚɰɢʁɟ ɭ ɩɨɪɟђɟʃɭ ɫɚ ɩɪɟɨɩɟɪɚɬɢɜɧɢɦ ɜɪɟɞɧɨɫɬɢɦɚ, ɱɢɦɟ ʁɟ ɩɨɬɜɪђɟɧɨ ɬɭɦɨɪɫɤɨ ɩɨɪɟɤɥɨ ɩɪɨɬɟɢɧɚ121,159,160,161. Ⱦɨɤɚɡɚɧɚ ʁɟ ɩɨɜɟɡɚɧɨɫɬ ɢɡɦɟђɭ ɤɨɧɰɟɧɬɪɚɰɢʁɟ ɨɜɨɝ ɛɢɨɦɚɪɤɟɪɚ ɭ ɭɪɢɧɭ ɢ ɜɟɥɢɱɢɧɟ ɢ ɯɢɫɬɨɥɨɲɤɨɝ ɫɬɚɞɢʁɭɦɚ ɬɭɦɨɪɚ, ɚɥɢ ɧɟ ɢ ɝɪɚɞɭɫɚ ɬɭɦɨɪɚ. ɍ ɫɜɢɦ ɫɬɭɞɢʁɚɦɚ ɤɨɧɰɟɧɬɪɚɰɢʁɚ AQP-1 ɭ ɭɪɢɧɭ ɨɞɪɟђɟɧɚ ʁɟɫɩɟɰɢɮɢɱɧɢɦ Western blot ɬɟɫɬɨɦ, ɭɡ ɡɚɤʂɭɱɚɤ ɚɭɬɨɪɚ ɞɚ ʁɟ ɬɟɫɬ ɝɥɨɦɚɡɚɧ, ɡɛɨɝ ɱɟɝɚ ʁɟ ɧɟɨɩɯɨɞɧɨ ɨɞɪɟђɢɜɚʃɟ AQP-1 ɭ ɭɪɢɧɭ ɩɪɢɦɟɧɨɦ ɫɟɧɡɢɬɢɜɧɨɝ ɢ ɫɩɟɰɢɮɢɱɧɨɝ ELISA ɬɟɫɬɚ. ɇɚ ɬɚʁ ɧɚɱɢɧ ɨɦɨɝɭʄɢɥɨ ɛɢ ɫɟ ɛɨʂɟ ɤɜɚɧɬɢɬɚɬɢɜɧɨ ɨɞɪɟђɢɜɚʃɟ ɨɜɨɝ ɭɪɢɧɚɪɧɨɝ ɛɢɨɦɚɪɤɟɪɚ. 1.8. Ʌȿɑȿȵȿ Ɍɟɪɚɩɢʁɫɤɢ ɩɪɢɫɬɭɩɢ ɭ ɥɟɱɟʃɭ ɤɚɪɰɢɧɨɦɚ ɛɭɛɪɟɝɚ ɪɚɡɥɢɤɭʁɭ ɫɟ ɭ ɡɚɜɢɫɧɨɫɬɢ ɨɞ ɬɨɝɚ ɞɚ ɥɢ ʁɟ ɛɨɥɟɫɬ ɨɪɝɚɧ-ɨɝɪɚɧɢɱɟɧɚ ɬʁ. ɥɨɤɚɥɢɡɨɜɚɧɚ ɢɥɢ ɦɟɬɚɫɬɚɬɫɤɚ. 1.8.1. Ɍɟɪɚɩɢʁɫɤɢ ɩɪɢɫɬɭɩɢ ɭ ɥɟɱɟʃɭ ɥɨɤɚɥɢɡɨɜɚɧɟ ɛɨɥɟɫɬɢ Ɍɟɪɚɩɢʁɫɤɢ ɩɪɢɫɬɭɩɢ ɭ ɥɟɱɟʃɭ ɥɨɤɚɥɢɡɨɜɚɧɨɝ ɄȻ ɦɨɝɭ ɛɢɬɢ: ɚɤɬɢɜɧɨ ɩɪɚʄɟʃɟ, ɩɚɪɰɢʁɚɥɧɚ ɧɟɮɪɟɤɬɨɦɢʁɚ (ɉɇ) ɢ ɪɚɞɢɤɚɥɧɚ ɧɟɮɪɟɤɬɨɦɢʁɚ (Ɋɇ). Ⱥɤɬɢɜɧɨ ɩɪɚʄɟʃɟ ɫɟ ɞɟɮɢɧɢɲɟ ɤɚɨ ɩɪɚʄɟʃɟ ɜɟɥɢɱɢɧɟ ɬɭɦɨɪɚ ɛɭɛɪɟɝɚ ɩɪɢɦɟɧɨɦ ɪɚɡɥɢɱɢɬɢɯ ɪɚɞɢɨɥɨɲɤɢɯ ɬɟɯɧɢɤɚ ɡɚ ɩɪɟɝɥɟɞ ɚɛɞɨɦɟɧɚ (ɍɋ, ɄɌ ɢɥɢ ɆɊ), ɫɚ ɨɞɥɚɝɚʃɟɦ ɥɟɱɟʃɚ ɞɨ ɬɪɟɧɭɬɤɚ ɤɚɞɚ ɬɭɦɨɪ ɩɨɤɚɠɟ ɤɥɢɧɢɱɤɭ ɩɪɨɝɪɟɫɢʁɭ. ɉɪɢɦɟʃɭʁɟ ɫɟ ɤɨɞ ɫɬɚɪɢʁɢɯ ɩɚɰɢʁɟɧɚɬɚ ɫɚ ɛɪɨʁɧɢɦ ɤɨɦɨɪɛɢɞɧɢɦ ɫɬɚʃɢɦɚ ɢ ɜɢɫɨɤɢɦ ɨɩɟɪɚɬɢɜɧɢɦ ɪɢɡɢɤɨɦ162,163. ɍȼɈȾ 22 Ⱦɟɰɟɧɢʁɚɦɚ ʁɟ Ɋɇ ɛɢɥɚ ɡɥɚɬɧɢ ɫɬɚɧɞɚɪɞ ɭ ɨɩɟɪɚɬɢɜɧɨɦ ɥɟɱɟʃɭ ɬɭɦɨɪɚ ɛɭɛɪɟɝɚ. Ɉɫɚɦɞɟɫɟɬɢɯ ɝɨɞɢɧɚ ɩɪɨɲɥɨɝ ɜɟɤɚ ɨɜɚʁ ɩɪɢɫɬɭɩ ʁɟ ɢɡɦɟʃɟɧ ɩɪɢɦɟɧɨɦ ɉɇ ɤɨɞ ɩɚɰɢʁɟɧɚɬɚ ɫɚ ɫɨɥɢɬɚɪɧɢɦ ɛɭɛɪɟɝɨɦ, ɚ ɩɨɫɥɟɞʃɢɯ 10-ɬɚɤ ɝɨɞɢɧɚ ɨɧɚ ɩɨɫɬɚʁɟ ɫɬɚɧɞɚɪɞ ɭ ɥɟɱɟʃɭ ɦɚɥɢɯ ɬɭɦɨɪɫɤɢɯ ɩɪɨɦɟɧɚ. ȼɟɥɢɱɢɧɚ ɬɭɦɨɪɚ ɫɟ ɜɢɲɟ ɧɟ ɫɦɚɬɪɚ ɨɝɪɚɧɢɱɚɜɚʁɭʄɢɦ ɮɚɤɬɨɪɨɦ ɡɚ ɉɇ, ɬɟ ɫɟ ɨɜɚʁ ɜɢɞ ɯɢɪɭɪɲɤɨɝ ɥɟɱɟʃɚ ɩɪɟɞɥɚɠɟ ɤɚɞɝɨɞ ʁɟ ɬɨ ɦɨɝɭʄɟ ɢ ɢɡɜɨɞʂɢɜɨ164. ɉɪɟɦɚ ɩɪɟɩɨɪɭɤɚɦɚ ȼɨɞɢɱɚ ɡɚ ɤɚɪɰɢɧɨɦɚ ɛɭɛɪɟɝɚ ȿɜɪɨɩɫɤɨɝ ɭɞɪɭɠɟʃɚ ɭɪɨɥɨɝɚ, ɉɇ ʁɟ ɢɧɞɢɤɨɜɚɧɚ: ɤɨɞ ɩɚɰɢʁɟɧɚɬɚ ɫɚ ɧɢɫɤɢɦ ɫɬɚɞɢʁɭɦɨɦ ɛɨɥɟɫɬɢ (Ɍ1ɚ) ɢ ɤɨɞ ɫɨɥɢɬɚɪɧɢɯ ɬɭɦɨɪɚ ɛɭɛɪɟɝɚ ɞɢʁɚɦɟɬɪɚ ɞɨ 7 cm, ɤɚɞ ɝɨɞ ʁɟ ɬɨ ɬɟɯɧɢɱɤɢ ɦɨɝɭʄɟ49. Ɉɩɟɪɚɬɢɜɧɟ ɬɟɯɧɢɤɟ ɉɇ ɦɨɝɭ ɛɢɬɢ: ɨɬɜɨɪɟɧɚ ɉɇ, ɥɚɩɚɪɨɫɤɨɩɫɤɚ ɉɇ ɢ ɪɨɛɨɬ-ɚɫɢɫɬɢɪɚɧɚ ɉɇ165,166. Ɋɚɞɢɤɚɥɧɚ ɧɟɮɪɟɤɬɨɦɢʁɚ ʁɟ ɫɬɚɧɞɚɪɞɧɚ ɯɢɪɭɪɲɤɚ ɩɪɨɰɟɞɭɪɚ ɡɚ ɥɟɱɟʃɟ ɩɚɰɢʁɟɧɚɬɚ ɫɚ ɬɭɦɨɪɨɦ ɛɭɛɪɟɝɚ ɭ Ɍ2 ɫɬɚɞɢʁɭɦɭ ɛɨɥɟɫɬɢ, ɤɚɨ ɢ ɨɧɢɯ ɬɭɦɨɪɫɤɢɯ ɩɪɨɦɟɧɚ ɤɨʁɟ ɫɟ ɧɟ ɦɨɝɭ ɥɟɱɢɬɢ ɩɪɢɦɟɧɨɦ ɉɇ49. Ɉɩɟɪɚɬɢɜɧɟ ɬɟɯɧɢɤɟ Ɋɇ ɦɨɝɭ ɛɢɬɢ: ɨɬɜɨɪɟɧɚ Ɋɇ, ɫɬɚɧɞɚɪɞɧɚ ɥɚɩɚɪɨɫɤɨɩɫɤɚ Ɋɇ, ɪɭɱɧɨ-ɚɫɢɫɬɢɪɚɧɚ ɥɚɩɚɪɨɫɤɨɩɫɤɚ Ɋɇ ɢ ɪɨɛɨɬ-ɚɫɢɫɬɢɪɚɧɚ ɥɚɩɚɪɨɫɤɨɩɫɤɚ Ɋɇ167. 1.8.2. Ɍɟɪɚɩɢʁɫɤɢ ɩɪɢɫɬɭɩɢ ɭ ɥɟɱɟʃɭ ɦɟɬɚɫɬɚɬɫɤɟ ɛɨɥɟɫɬɢ ɏɢɪɭɪɲɤɨ ɥɟɱɟʃɟ ɦɟɬɚɫɬɚɬɫɤɨɝ ɄȻ ɍ ɯɢɪɭɪɲɤɨɦ ɥɟɱɟʃɭ ɦɟɬɚɫɬɚɬɫɤɨɝ ɄȻ ɩɪɢɦɟʃɭʁɭ ɫɟ: ɬɭɦɨɪ ɢɥɢ ɰɢɬɨɪɟɞɭɤɬɢɜɧɚ ɧɟɮɪɟɤɬɨɦɢʁɚ ɢ ɦɟɬɚɫɬɚɡɟɤɬɨɦɢʁɚ. Ɂɚ ɜɟʄɢɧɭ ɩɚɰɢʁɟɧɚɬɚ ɫɚ ɦɟɬɚɫɬɚɬɫɤɨɦ ɛɨɥɟɲʄɭ, ɰɢɬɨɪɟɞɭɤɬɢɜɧɚ ɧɟɮɪɟɤɬɨɦɢʁɚ ʁɟ ɩɚɥɢʁɚɬɢɜɧɚ ɦɟɬɨɞɚ ɥɟɱɟʃɚ, ɭɡ ɧɟɨɩɯɨɞɧɭ ɩɪɢɦɟɧɭ ɫɢɫɬɟɦɫɤɟ ɬɟɪɚɩɢʁɟ168. Ɇɟɬɚɫɬɚɡɟɤɬɨɦɢʁɚ ɦɨɠɟ ɛɢɬɢ ɤɨɦɩɥɟɬɧɚ ɢ ɩɚɪɰɢʁɚɥɧɚ169,170. ɉɪɢɦɟʃɭʁɟ ɫɟ ɤɚɞɚ ɫɭ: ɩɪɨɦɟɧɟ ɪɟɫɟɤɬɚɛɢɥɧɟ, ɚ ɩɚɰɢʁɟɧɬ ɢɦɚ ɞɨɛɚɪ ɨɩɲɬɢ ɫɬɚɬɭɫ ɢ ɤɨɞ ɩɚɰɢʁɟɧɚɬɚ ɫɚ ɡɚɨɫɬɚɥɢɦ ɢ ɪɟɫɟɤɬɚɛɢɥɧɢɦ ɦɟɬɚɫɬɚɬɫɤɢɦ ɩɪɨɦɟɧɚɦɚ, ɧɚɤɨɧ ɩɪɢɦɟɧɟ ɢɦɭɧɨɬɟɪɚɩɢʁɟ ɢ/ɢɥɢ ɞɪɭɝɟ ɫɢɫɬɟɦɫɤɟ ɬɟɪɚɩɢʁɟ49. ɋɢɫɬɟɦɫɤɚ ɬɟɪɚɩɢʁɚ ɦɟɬɚɫɬɚɬɫɤɨɝ ɄȻ Ɍɟɪɚɩɢʁɚ ɦɟɬɚɫɬɚɬɫɤɨɝ ɤɚɪɰɢɧɨɦɚ ɛɭɛɪɟɝɚ (ɦɄȻ) ʁɟ ɡɧɚɱɚʁɧɨ ɧɚɩɪɟɞɨɜɚɥɚ, ɩɪɟɬɜɚɪɚʁɭʄɢ ɩɨɬɟɧɰɢʁɚɥɧɨ ɫɦɪɬɨɧɨɫɧɨ ɫɬɚʃɟ ɭ ɯɪɨɧɢɱɧɭ ɛɨɥɟɫɬ. Ⱦɨ ɫɪɟɞɢɧɟ ɩɪɨɲɥɟ ɞɟɰɟɧɢʁɟ, ɢɦɭɧɨɬɟɪɚɩɢʁɚ ɫɚ ɢɧɬɟɪɥɟɭɤɢɧɨɦ-2 (IL-2) ɢɥɢ ɢɧɬɟɪɮɟɪɨɧɨɦ-ɚɥɮɚ (IFN-α) ɛɢɥɚ ʁɟ ɫɬɚɧɞɚɪɞɧɚ ɬɟɪɚɩɢʁɚ ɭ ɥɟɱɟʃɭ ɩɚɰɢʁɟɧɚɬɚ ɫɚ ɦɄȻ171,172. Ɂɧɚɱɚʁɚɧ ɧɚɩɪɟɞɚɤ ɭ ɬɟɪɚɩɢʁɢ ɦɄȻ ɩɨɫɬɢɝɧɭɬ ʁɟ ɧɚɤɨɧ ɪɚɫɜɟɬʂɚɜɚʃɚ ɦɨɥɟɤɭɥɚɪɧɟ ɛɢɨɥɨɝɢʁɟ ɄȻ, ɲɬɨ ʁɟ ɞɨɜɟɥɨ ɞɨ ɩɪɢɦɟɧɟ ɰɢʂɧɟ ɬɟɪɚɩɢʁɟ. Ⱦɜɟ ɨɫɧɨɜɧɟ ɝɪɭɩɟ ɥɟɤɨɜɚ ɤɨʁɢ ɫɟ ɩɪɢɦɟʃɭʁɭ ɭ ɰɢʂɧɨʁ ɬɟɪɚɩɢʁɢ ɦɄȻ ɫɭ: ɢɧɯɢɛɢɬɨɪɢ ɬɢɪɨɡɢɧ ɤɢɧɚɡɚ ɢ mTOR (ɟɧɝɥ. ɫɤɪ. mammalian target of rapamycin) ɢɧɯɢɛɢɬɨɪɢ. ɋɥɟɞɟʄɢ ɰɢʂɧɢ ɥɟɤɨɜɢ ɢɡ ɝɪɭɩɟ ɬɢɪɨɡɢɧ ɤɢɧɚɡɚ ɨɞɨɛɪɟɧɢ ɫɭ ɭ ȿɜɪɨɩɢ ɢ ɋȺȾ ɡɚ ɥɟɱɟʃɟ ɦɄȻ: ɋɨɪɚɮɟɧɢɛ, ɋɭɧɢɬɢɧɢɛ, ɉɚɡɨɩɚɧɢɛ, Ⱥɤɫɢɬɢɧɢɛ ɢ Ȼɟɜɚɰɢɡɭɦɚɛ173,174,175,176. ɂɡɭɡɟɜ Ȼɟɜɚɰɢɡɭɦɚɛ-ɚ ɤɨʁɢ ʁɟ ɦɨɧɨɤɥɨɧɫɤɨ ɚɧɬɢ-VEGF ɚɧɬɢɬɟɥɨ, ɨɫɬɚɥɢ ɥɟɤɨɜɢ ɫɭ ɢɧɯɢɛɢɬɨɪɢ ɪɚɡɥɢɱɢɬɢɯ ɬɢɪɨɡɢɧ ɤɢɧɚɡɚ ɢ ɩɪɢɦɟʃɭʁɭ ɫɟ ɭ ɩɟɪɨɪɚɥɧɨɦ ɨɛɥɢɤɭ. Ɉɞ mTOR ɢɧɯɢɛɢɬɨɪɚ ɭ ɩɪɢɦɟɧɢ ɫɭ ɞɜɚ, ɬɟɦɫɢɪɨɥɢɦɭɫ ɢ ɟɜɟɪɨɥɢɦɭɫ177,178. ɍȼɈȾ 23 ɍ ɬɚɛɟɥɢ ɛɪ. 3. ɞɚɬ ʁɟ ɚɥɝɨɪɢɬɚɦ ɩɪɢɦɟɧɟ ɬɟɪɚɩɢʁɟ ɤɨɞ ɩɚɰɢʁɟɧɚɬɚ ɫɚ ɦɄȻ179. Ɍɚɛɟɥɚ ɛɪ.3. Аɥɝɨɪɢɬɚɦ ɬɟɪɚɩɢʁɟ ɤɨɞ ɩɚɰɢʁɟɧɚɬɚ ɫɚ ɦɟɬɚɫɬɚɬɫɤɢɦ ɤɚɪɰɢɧɨɦɨɦ ɛɭɛɪɟɝɚ Ɍɟɪɚɩɢʁɚ ɋɬɚʃɟ ɇɢɜɨ ɞɨɤɚɡɚ I ɇɢɜɨ ɞɨɤɚɡɚ II Ⱦɨɛɪɚ ɩɪɨɝɧɨɡɚ Sunitinib Sorafenib ɉɪɜɚ ɥɢɧɢʁɚ ɬɟɪɚɩɢʁɚ ɍɦɟɪɟɧ ɪɢɡɢɤ Bevacizumab/Interferon Pazopanib ȼɢɫɨɤɟ ɞɨɡɟ IL-2 Ʌɨɲɚ ɩɪɨɝɧɨɡɚ Temsirolimus Sunitinib Sorafenib Ɋɟɮɪɚɤɬɟɪɧɨɫɬ ɧɚ ɰɢɬɨɤɢɧɫɤɭ ɬɟɪɚɩ. Sorafenib Pazopanib Sunitinib Ⱦɪɭɝɚ ɥɢɧɢʁɚ ɬɟɪɚɩɢʁɟ Ɋɟɡɢɫɬɟɧɰɢʁɚ ɧɚ ɌɄɂ Axitinib Everolimus Sorafenib ɉɪɟ mTor ɢɧɯɢɛɢɬɨɪɚ Sunitinib ɌɄɂ:ɢɧɯɢɛɢɬɨɪɢ ɬɢɪɨɡɢɧ ɤɢɧɚɡɟ 1.9. ɉɪɨɝɧɨɫɬɢɱɤɢ ɮɚɤɬɨɪɢ Ɏɚɤɬɨɪɢ ɤɨʁɢ ɭɬɢɱɭ ɧɚ ɩɪɨɝɧɨɡɭ ɩɚɰɢʁɟɧɚɬɚ ɨɛɨɥɟɥɢɯ ɨɞ ɄȻ ɦɨɝɭ ɫɟ ɩɨɞɟɥɢɬɢ ɧɚ: ɚɧɚɬɨɦɫɤɟ, ɯɢɫɬɨɥɨɲɤɟ, ɤɥɢɧɢɱɤɟ ɢ ɦɨɥɟɤɭɥɚɪɧɟ. 1.9.1. Ⱥɧɚɬɨɦɫɤɢ ɩɪɨɝɧɨɫɬɢɱɤɢ ɮɚɤɬɨɪɢ Ⱥɧɚɬɨɦɫɤɢ ɮɚɤɬɨɪɢ ɨɞɧɨɫɟ ɫɟ ɧɚ: ɜɟɥɢɱɧɭ ɬɭɦɨɪɚ, ɬɭɦɨɪɫɤɭ ɢɧɜɚɡɢʁɭ ɜɟɧɫɤɢɯ ɤɪɜɧɢɯ ɫɭɞɨɜɚ, ɛɭɛɪɟɠɧɟ ɤɚɩɫɭɥɟ, ɡɚɯɜɚɬɚʃɟ ɧɚɞɛɭɛɪɟɠɧɢɯ ɠɥɟɡɞɚ, ɥɢɦɮɧɢɯ ɱɜɨɪɨɜɚ ɢ ɩɨɫɬɨʁɚʃɟ ɭɞɚʂɟɧɢɯ ɦɟɬɚɫɬɚɡɚ. ɋɜɢ ɧɚɜɟɞɟɧɢ ɮɚɤɬɨɪɢ ɫɭ ɨɛʁɟɞɢʃɟɧɢ ɭ ʁɟɞɢɧɫɬɜɟɧɢ, ɧɚʁɲɢɪɟ ɤɨɪɢɲʄɟɧɢ, ɌNМ (ɟɧɝɥ. ɫɤɪ. Tumor-Node-Metastasis) ɤɥɚɫɢɮɢɤɚɰɢɨɧɢ ɫɢɫɬɟɦ. Ɉɞ 1.01.2010. ɭ ɭɩɨɬɪɟɛɢ ʁɟ ɫɟɞɦɚ ɌNМ ɤɥɚɫɢɮɢɤɚɰɢʁɟ ɡɚ ɄȻ180,181. (Ɍɚɛɟɥɚ ɛɪ. 4.) ɍȼɈȾ 24 Ɍɚɛɟɥɚ ɛɪ. 4. ɋɟɞɦɚ ɌNM ɤɥɚɫɢɮɢɤɚɰɢʁɚ ɤɚɪɰɢɧɨɦɚ ɛɭɛɪɟɝɚ Ɍ-ɩɪɢɦɚɪɧɢ ɬɭɦɨɪ Tx ɇɢʁɟ ɦɨɝɭʄɚ ɩɪɨɰɟɧɚ ɩɪɢɦɚɪɧɨɝ ɬɭɦɨɪɚ T0 ɇɟɦɚ ɡɧɚɤɨɜɚ ɩɪɢɦɚɪɧɨɝ ɬɭɦɨɪɚ Ɍ1 Ɍɭɦɨɪ < 7 ɰɦ ɭ ɧɚʁɜɟʄɟɦ ɩɪɨɦɟɪɭ, ɨɝɪɚɧɢɱɟɧ ɧɚ ɛɭɛɪɟɝ Ɍ1ɚ-Ɍɭɦɨɪ ≤ 4 ɰɦ ɭ ɧɚʁɜɟʄɟɦ ɩɪɨɦɟɪɭ, ɨɝɪɚɧɢɱɟɧ ɧɚ ɛɭɛɪɟɝ Ɍ1ɛ-Ɍɭɦɨɪ > 4 ɰɦ ɚɥɢ ≤ 7 ɰɦ ɭ ɧɚʁɜɟʄɟɦ ɩɪɨɦɟɪɭ Ɍ2 Ɍɭɦɨɪ > 7 ɰɦ ɭ ɧɚʁɜɟʄɟɦ ɩɪɨɦɟɪɭ, ɨɝɪɚɧɢɱɟɧ ɧɚ ɛɭɛɪɟɝ Ɍ2ɚ-Ɍɭɦɨɪ > 7 ɰɦ ɚɥɢ ≤ 10 ɰɦ ɭ ɧɚʁɜɟʄɟɦ ɩɪɨɦɟɪɭ Ɍ2ɛ-Ɍɭɦɨɪɢ > 10 ɰɦ, ɨɝɪɚɧɢɱɟɧɢ ɧɚ ɛɭɛɪɟɝ Ɍ3 Ɍɭɦɨɪ ɫɟ ɩɪɭɠɚ ɭ ɝɥɚɜɧɟ ɜɟɧɟ ɢɥɢ ɩɟɪɢɧɟɮɪɢɬɢɱɤɨ ɬɤɢɜɨ ɚɥɢ ɫɟ ɧɟ ɲɢɪɢ ɭ ɢɩɫɢɥɚɬɟɪɚɥɧɭ ɧɚɞɛɭɛɪɟɠɧɭ ɠɥɟɡɞɭ ɢ ɢɡɜɚɧ Ƚɟɪɨɬɚ ɮɚɫɰɢʁɟ Ɍ3ɚ-Ɍɭɦɨɪ ɫɟ ɲɢɪɢ ɭ ɪɟɧɚɥɧɭ ɜɟɧɭ ɢɥɢ ʃɟɧɟ ɫɟɝɦɟɧɬɧɟ, ɦɢɲɢʄɧɟ ɝɪɚɧɟ ɢɥɢ ɬɭɦɨɪ ɡɚɯɜɚɬɚ ɩɟɪɢɪɟɧɚɥɧɨ ɢ/ɢɥɢ ɦɚɫɧɨ ɬɤɢɜɨ ɛɭɛɪɟɠɧɨɝ ɫɢɧɭɫɚ ɚɥɢ ɧɟ ɢɡɜɚɧ Ƚɟɪɨɬɚ ɮɚɫɰɢʁɟ Ɍ3ɛ-Ɍɭɦɨɪ ʁɟ ɩɪɨɲɢɪɟɧ ɭ ɞɨʃɭ ɲɭɩʂɭ ɜɟɧɭ ɢɫɩɨɞ ɞɢʁɚɮɪɚɝɦɟ Ɍ3ɰ-Ɍɭɦɨɪ ʁɟ ɩɪɨɲɢɪɟɧ ɭ ɞɨʃɭ ɲɭɩʂɭ ɜɟɧɭ ɢɡɧɚɞ ɞɢʁɚɮɪɚɝɦɟ ɢɥɢ ɡɚɯɜɚɬɚ ɡɢɞ ɜɟɧɟ ɤɚɜɟ Ɍ4 Ɍɭɦɨɪ ɫɟ ɲɢɪɢ ɢɡɜɚɧ Ƚɟɪɨɬɚ ɮɚɫɰɢʁɟ (ɭɤʂɭɱɭʁɭʄɢ ɤɨɧɬɢɧɭɢɪɚɧɨ ɲɢɪɟʃɟ ɭ ɢɩɫɢɥɚɬɟɪɚɥɧɭ ɧɚɞɛɭɛɪɟɠɧɭ ɠɥɟɡɞɭ) N-ɪɟɝɢɨɧɚɥɧɢ ɥɢɦɮɧɢ ɱɜɨɪɨɜɢ NX ɪɟɝɢɨɧɚɥɧɢ ɥɢɦɮɧɢ ɱɜɨɪɨɜɢ ɧɢɫɭ ɞɨɫɬɭɩɧɢ ɡɚ ɚɧɚɥɢɡɭ N0 ɛɟɡ ɦɟɬɚɫɬɚɡɚ ɭ ɪɟɝɢɨɧɚɥɧɢɦ ɥɢɦɮɧɢɦ ɱɜɨɪɨɜɢɦɚ N1 ɦɟɬɚɫɬɚɡɚ ɭ ʁɟɞɧɨɦ ɪɟɝɢɨɧɚɥɧɨɦ ɥɢɦɮɧɨɦ ɱɜɨɪɭ N2 ɦɟɬɚɫɬɚɡɚ ɭ ɜɢɲɟ ɨɞ 1 ɥɢɦɮɧɨɝ ɱɜɨɪɚ Ɇ-ɭɞɚʂɟɧɟ ɦɟɬɚɫɬɚɡɟ Ɇ0 ɛɟɡ ɭɞɚʂɟɧɢɯ ɦɟɬɚɫɬɚɡɚ Ɇ1 ɭɞɚʂɟɧɟ ɦɟɬɚɫɬɚɡɟ TNMɫɬɚɞɢʁɭɦɢ ɋɬɚɞɢʁɭɦ I T1 N0 M0 ɋɬɚɞɢʁɭɦ II T2 N0 M0 ɋɬɚɞɢʁɭɦ III T1-2 N1 M0 Ɍ3 N0-1 M0 ɋɬɚɞɢʁɭɦ IV T4 N2 M0 T (ɛɢɥɨ ɤɨʁɢ) N (ɛɢɥɨ ɤɨʁɢ) M1 1.9.2. ɏɢɫɬɨɥɨɲɤɢ ɩɪɨɝɧɨɫɬɢɱɤɢ ɮɚɤɬɨɪɢ ɏɢɫɬɨɥɨɲɤɢ ɮɚɤɬɨɪɢ ɫɟ ɨɞɧɨɫɟ ɧɚ: Fuhrman-ɨɜ ɧɭɤɥɟɚɪɧɢ ɫɬɚɞɢʁɭɦ, ɯɢɫɬɨɥɨɲɤɢ ɩɨɞɬɢɩ, ɫɚɪɤɨɦɚɬɨɢɞɧɟ ɩɪɨɦɟɧɟ, ɦɢɤɪɨɜɚɫɤɭɥɚɪɧɭ ɢɧɜɚɡɢʁɭ, ɬɭɦɨɪɫɤɭ ɧɟɤɪɨɡɭ ɢ ɢɧɜɚɡɢʁɭ ɫɚɛɢɪɧɨɝ ɫɢɫɬɟɦɚ. Fuhrman-ɨɜ ɫɢɫɬɟɦ ɨɞɪɟђɢɜɚʃɚ ɫɬɚɞɢʁɭɦɚ ɤɚɪɰɢɧɨɦɚ ɛɭɛɪɟɝɚ ɧɚ ɨɫɧɨɜɭ ɜɟɥɢɱɢɧɟ ɢ ɢɡɝɥɟɞɚ ʁɟɞɪɚ ɬɭɦɨɪɫɤɢɯ ʄɟɥɢʁɚ ɢ ɢɡɪɚɠɚʁɧɨɫɬɢ ɧɭɤɥɟɨɥɭɫɚ, ɲɢɪɨɤɨ ʁɟ ɩɪɢɯɜɚʄɟɧ ɭ ɩɚɬɨɥɨɲɤɨʁ ɩɪɚɤɫɢ ɢ ɩɪɟɞɫɬɚɜʂɚ ɧɟɡɚɜɢɫɧɢ ɩɪɟɞɢɤɬɨɪ ɩɪɟɠɢɜʂɚɜɚʃɚ ɨɜɢɯ ɩɚɰɢʁɟɧɚɬɚ. ɍȼɈȾ 25 Ɉɩɢɫɚɧ ʁɟ ɩɪɜɢ ɩɭɬ 1982. ɨɞ ɫɬɪɚɧɟ Susan Fuhrman ɢ ɧɚɞɚʂɟ ɩɪɟɞɫɬɚɜʂɚ ɧɚʁɱɟɲʄɟ ɤɨɪɢɲʄɟɧ ɫɢɫɬɟɦ ɡɚ ɭɬɜɪђɢɜɚʃɟ ɝɪɚɞɭɫɚ ɤɚɪɰɢɧɨɦɚ ɛɭɛɪɟɝɚ182 (Ɍɚɛɟɥɚ ɛɪ. 5). ɇɚ ɨɫɧɨɜɭ ɧɚɜɟɞɟɧɢɯ ɤɪɢɬɟɪɢʁɭɦɚ ɤɚɪɰɢɧɨɦ ɛɭɛɪɟɝɚ ɫɟ ɞɟɥɢ ɭ 4 ɫɬɚɞɢʁɭɦɚ: Ɍɚɛɟɥɚ ɛɪ. 5. Хɢɫɬɨɥɨɲɤɢ ɧɭɤɥɟɚɪɧɢ ɫɬɚɞɢʁɭɦɢ ɩɨ Fuhrman-ɭ ɇɭɤɥɟɚɪɧɢ ɫɬɚɞɢʁɭɦɢ ɩɨ Fuhrman-ɭ ɂɡɝɥɟɞ ʁɟɞɚɪɚ ɦɚɥɢɝɧɢɯ ʄɟɥɢʁɚ Ƚɪɚɞɭɫ 1 (G1) ʁɟɞɪɚ ɬɭɦɨɪɫɤɢɯ ʄɟɥɢʁɚ ɫɭ ɦɚɥɚ (<10 µЦ), ɯɢɩɟɪɯɪɨɦɚɬɫɤɚ, ɭɧɢɮɨɪɦɧɚ, ɨɤɪɭɝɥɚ (ɩɨɞɫɟʄɚʁɭ ɧɚ ɡɪɟɥɟ ɥɢɦɮɨɰɢɬɟ), ɛɟɡ ɜɢɞʂɢɜɢɯ ɧɭɤɥɟɨɥɭɫɚ Ƚɪɚɞɭɫ 2 (G2) ʁɟɞɪɚ ɬɭɦɨɪɫɤɢɯ ʄɟɥɢʁɚ ɫɭ ɜɟʄɚ (15 µЦ), ɫɚ ɝɪɚɧɭɥɚɪɧɢɦ, ɫɥɨɛɨɞɧɢɦ ɯɪɨɦɚɬɢɧɨɦ ɢ ɦɚɥɢɦ, ɧɟɭɩɚɞʂɢɜɢɦ ɧɭɤɥɟɨɥɭɫɢɦɚ Ƚɪɚɞɭɫ 3 (G3) ʁɟɞɪɚ ɬɭɦɨɪɫɤɢɯ ʄɟɥɢʁɚ ɫɭ ɜɟʄɚ (20 µЦ), ɦɨɝɭ ɛɢɬɢ ɨɜɚɥɧɨɝ ɨɛɥɢɤɚ, ɫɚ ɝɪɭɛɨ ɝɪɚɧɭɥɚɪɧɢɦ ɯɪɨɦɚɬɢɧɨɦ ɢ ɥɚɤɨ ɭɨɱʂɢɜɢɦ, ɭɧɢɮɨɪɦɧɢɦ ɧɭɤɥɟɨɥɭɫɢɦɚ Ƚɪɚɞɭɫ 4 (G4) ɜɢɞʂɢɜɟ ɫɭ ɦɢɬɨɡɟ, ʁɟɞɪɚ ɫɭ ɛɢɡɚɪɧɚ, ɩɥɟɨɦɨɪɮɧɚ, ɫɚ ɫɥɨɛɨɞɧɢɦ ɯɪɨɦɚɬɢɧɨɦ ɢɥɢ ɯɢɩɟɪɯɪɨɦɚɬɫɤɚ, ɫɚ ʁɟɞɧɢɦ ɢɥɢ ɜɢɲɟ ɦɚɤɪɨɧɭɤɥɟɨɥɭɫɚ Ɋɟɡɭɥɬɚɬɢ ɧɟɞɚɜɧɨ ɫɩɪɨɜɟɞɟɧɢɯ ɫɬɭɞɢʁɚ ɫɭ ɩɨɤɚɡɚɥɢ ɞɚ ʁɟ ɤɥɚɫɢɱɚɧ Fuhrman-ɨɜ ɫɢɫɬɟɦ ɤɨɦɩɥɟɤɫɚɧ ɢ ɞɚ ɫɟ ɦɨɠɟ ɦɨɞɢɮɢɤɨɜɚɬɢ. Ɇɨɞɢɮɢɤɚɰɢʁɚ Fuhrman-ɨɜɨɝ ɫɢɫɬɟɦɚ ɩɨɞɪɚɡɭɦɟɜɚ ɞɚ ɫɟ ɫɬɚɞɢʁɭɦɢ 1 ɢ 2 ɡɛɨɝ ɦɚɥɢɯ ɪɚɡɥɢɤɚ ɢɡɪɚɠɚɜɚʁɭ ɤɚɨ ʁɟɞɚɧ ɫɬɚɞɢʁɭɦ, ɞɨɤ ɫɬɚɞɢʁɭɦɢ 3 ɢ 4 ɨɫɬɚʁɭ ɨɞɜɨʁɟɧɢ. ɍɬɜɪђɟɧɨ ʁɟ ɞɚ ɨɜɚɤɨ ɦɨɞɢɮɢɤɨɜɚɧ Fuhrman-ɨɜ ɫɢɫɬɟɦ ɩɪɟɞɫɬɚɜʂɚ ɧɟɡɚɜɢɫɧɢ ɩɪɟɞɢɤɬɨɪ ɩɪɟɠɢɜʂɚɜɚʃɚ ɢ ɩɨɡɢɬɢɜɧɨ ɤɨɪɟɥɢɪɚ ɫɚ ɪɟɤɭɪɟɧɰɢʁɨɦ ɛɨɥɟɫɬɢ. ɉɨɬɪɟɛɧɟ ɫɭ ɞɨɞɚɬɧɟ ɩɪɨɫɩɟɤɬɢɜɧɟ ɫɬɭɞɢʁɟ ɤɨʁɟ ɛɢ ɩɨɬɜɪɞɢɥɟ ɞɚɬɟ ɩɪɟɬɩɨɫɬɚɜɤɟ183. ɏɢɫɬɨɥɨɲɤɟ ɤɚɪɚɤɬɟɪɢɫɬɢɤɟ ɬɢɩɨɜɚ ɤɚɪɰɢɧɨɦɚ ɛɭɛɪɟɝɚ, ɞɢʁɚɝɧɨɫɬɢɱɤɢ ɤɪɢɬɟɪɢʁɭɦɢ ɢ ɩɪɨɝɧɨɡɚ, ɧɚɜɟɞɟɧɢ ɫɭ ɭ ɩɨɝɥɚɜʂɭ ɨ ɩɨɞɟɥɢ ɤɚɪɰɢɧɨɦɚ ɛɭɛɪɟɝɚ. 1.9.3. Ʉɥɢɧɢɱɤɢɩɪɨɝɧɨɫɬɢɱɤɢ ɮɚɤɬɨɪɢ Ʉɥɢɧɢɱɤɢ ɮɚɤɬɨɪɢ ɭɤʂɭɱɭʁɭ ɨɩɲɬɟ ɫɬɚʃɟ ɩɚɰɢʁɟɧɬɚ, ɥɨɤɚɥɧɟ ɫɢɦɩɬɨɦɟ, ɩɨɫɬɨʁɚʃɟ ɤɚɯɟɤɫɢʁɟ, ɚɧɟɦɢʁɭ ɢ ɛɪɨʁ ɬɪɨɦɛɨɰɢɬɚ. ɍ ɥɢɬɟɪɚɬɭɪɢ ɫɭ ɨɩɢɫɚɧɢ ɪɚɡɥɢɱɢɬɢ ɩɪɨɝɧɨɫɬɢɱɤɢ ɧɨɦɨɝɪɚɦɢ ɢɥɢ ɫɤɨɪɢɧɝ ɫɢɫɬɟɦɢ ɤɨʁɢ ɤɨɦɛɢɧɭʁɭ ɪɚɡɥɢɱɢɬɟ ɤɥɢɧɢɱɤɟ, ɩɚɬɨɥɨɲɤɟ ɢ ɦɨɥɟɤɭɥɚɪɧɟ ɦɚɪɤɟɪɟ ɭ ɰɢʂɭ ɭɬɜɪђɢɜɚʃɚ ɩɪɨɝɧɨɡɟ ɥɨɤɚɥɢɡɨɜɚɧɢɯ, ɥɨɤɚɥɧɨ ɭɡɧɚɩɪɟɞɨɜɚɥɢɯ ɢ ɦɟɬɚɫɬɚɬɫɤɢɯ ɤɚɪɰɢɧɨɦɚ ɛɭɛɪɟɝɚ. ɇɚʁɱɟɲʄɟ ɤɨɪɢɲʄɟɧɢ ɫɭ: ɢɧɬɟɝɪɢɫɚɧɢ ɫɬɚɞɢʁɭɦ ɫɢɫɬɟɦ ɍɧɢɜɟɪɡɢɬɟɬɚ ɭ Ʉɚɥɢɮɨɪɧɢʁɢ (ɟɧɝɥ. ɫɤɪ. UISS-University of California Integrated Staging System), ɫɬɚɞɢʁɭɦ, ɜɟɥɢɱɢɧɚ, ɝɪɚɞɭɫ ɢ ɧɟɤɪɨɡɚ ɫɤɨɪ Ɇɟʁɨ ɤɥɢɧɢɤɟ (ɟɧɝɥ.ɫɤɪ. SSIGN-the Mayo Clinic Stage, Size, Grade and Necrosis Score) ɢ Memorial Sloan- Kettering ɧɨɦɨɝɪɚɦ ɤɚɪɰɢɧɨɦɚ ɛɭɛɪɟɝɚ (ɟɧɝɥ. ɫɤɪ. MSKCC- Memorial Sloan-Kettering Renal Cell Carcinoma Nomogram)184.ɍ ɤɥɢɧɢɱɤɨʁ ɩɪɚɤɫɢ ɧɚʁɱɟɲʄɟ ʁɟ ɤɨɪɢɲʄɟɧ MSKCC ɧɨɦɨɝɪɚɦ ɤɨʁɢ ʁɟ ɭɫɬɚɧɨɜʂɟɧ ɨɞ ɫɬɪɚɧɟ Motzer ɢ ɫɚɪ. Ɉɧ ɭɤɥʂɭɱɭʁɟ ɩɟɬ ɮɚɤɬɨɪɚ ɪɢɡɢɤɚ: ɜɪɟɞɧɨɫɬ ɯɟɦɨɝɥɨɛɢɧɚ ɢɫɩɨɞ ɞɨʃɟ ɝɪɚɧɢɰɟ ɧɨɪɦɚɥɧɟ ɜɪɟɞɧɨɫɬɢ, ɤɨɪɢɝɨɜɚɧɚ ɜɪɟɞɧɨɫɬ ɫɟɪɭɦɫɤɨɝ ɤɚɥɰɢʁɭɦɚ ɜɢɲɚ ɨɞ 2,5mmol/l, ɜɪɟɞɧɨɫɬ ɥɚɤɬɚɬ ɞɟɯɢɞɪɨɝɟɧɚɡɟ ɩɨɜɢɲɟɧɚ 1,5 ɩɭɬ ɭ ɨɞɧɨɫɭ ɧɚ ɝɨɪʃɭ ɧɨɪɦɚɥɧɭ ɜɪɟɞɧɨɫɬ, Ʉɚɪɧɨɮɫɤɢ ɫɬɚɬɭɫ ɦɚʃɢ ɨɞ 80% ɢ ɜɪɟɦɟ ɨɞ ɞɢʁɚɝɧɨɡɟ ɞɨ ɍȼɈȾ 26 ɬɟɪɚɩɢʁɟ ɤɪɚʄɟ ɨɞ ʁɟɞɧɟ ɝɨɞɢɧɟ. ɇɚ ɨɫɧɨɜɭ ɡɛɢɪɚ ɧɚɜɟɞɟɧɢɯ ɮɚɤɬɨɪɚ ɪɢɡɢɤɚ ɩɚɰɢʁɟɧɬɢ ɨɛɨɥɟɥɢ ɨɞ ɄȻ ɦɨɝɭ ɫɟ ɩɨɞɟɥɢɬɢ ɭ ɝɪɭɩɟ ɫɚ: ɞɨɛɪɨɦ (ɧɢʁɟ ɩɪɢɫɭɬɚɧ ɧɢʁɟɞɚɧ ɨɞ ɮɚɤɬɨɪɚ ɪɢɡɢɤɚ), ɭɦɟɪɟɧɨ ɥɨɲɨɦ (ɩɪɢɫɭɬɧɚ ɫɭ 1 ɢɥɢ 2 ɮɚɤɬɨɪɚ ɪɢɡɢɤɚ) ɢ ɥɨɲɨɦ ɩɪɨɝɧɨɡɨɦ (ɩɪɢɫɭɬɧɚ ɫɭ 3 ɢɥɢ ɜɢɲɟ ɮɚɤɬɨɪɚ ɪɢɡɢɤɚ)185. 1.9.4. Ɇɨɥɟɤɭɥɚɪɧɢ ɩɪɨɝɧɨɫɬɢɱɤɢ ɦɚɪɤɟɪɢ Ȼɪɨʁɧɢ ɦɨɥɟɤɭɥɚɪɧɢ ɦɚɪɤɟɪɢ ɫɭ ɢɫɩɢɬɢɜɚɧɢ ɭ ɰɢʂɭ ɭɬɜɪђɢɜɚʃɚ ʃɢɯɨɜɨɝ ɡɧɚɱɚʁɚ ɡɚ ɩɪɨɝɧɨɡɭ ɨɛɨɥɟɥɢɯ ɨɞ ɄȻ, ɭɤʂɭɱɭʁɭʄɢ: ɭɝʂɟɧɭ ɚɧɯɢɞɪɚɡɭ IБ, VEGF, HIF, Ki-67, E- ɤɚɞɯɟɪɢɧ, CRP, ɚɞɯɟɡɢɨɧɢ ɦɨɥɟɤɭɥ CD44. Ɂɚ ɫɚɞɚ, ɧɢ ʁɟɞɚɧ ɢɫɩɢɬɢɜɚɧɢ ɦɨɥɟɤɭɥɚɪɧɢ ɦɚɪɤɟɪ ɧɢʁɟ ɩɨɤɚɡɚɨ ɩɪɟɞɢɤɬɢɜɧɭ ɜɪɟɞɧɨɫɬ ɡɚ ɩɪɨɝɧɨɡɭ ɨɛɨɥɟɥɢɯ ɨɞ ɄȻ, ɬɟ ɧɟ ɩɨɫɬɨʁɢ ɩɪɟɩɨɪɭɤɚ ɡɚ ʃɢɯɨɜɭ ɪɭɬɢɧɫɤɭ ɭɩɨɬɪɟɛɭ186. ɏɂɉɈɌȿɁȿ ɂ ɐɂȴȿȼɂ ɂɋɌɊȺɀɂȼȺȵȺ 27 2. ɏɂɉɈɌȿɁȿ ɂ ɐɂȴȿȼɂ ɂɋɌɊȺɀɂȼȺȵȺ ɇɚ ɨɫɧɨɜɭ ɩɨɞɚɬɚɤɚ ɢɡɧɟɬɢɯ ɭ ɭɜɨɞɭ, ɩɨɫɬɚɜʂɟɧɟ ɫɭ ɫɥɟɞɟʄɟ ɪɚɞɧɟ ɯɢɩɨɬɟɡɟ:  ɄɨɧɰɟɧɬɪɚɰɢʁɟKIM-1 ɢ AQP-1 ɭ ɭɪɢɧɭ ɩɚɰɢʁɟɧɚɬɚ ɫɚ ɤɚɪɰɢɧɨɦɨɦ ɫɜɟɬɥɢɯ ʄɟɥɢʁɚ ɛɭɛɪɟɝɚ ɫɭ ɡɧɚɱɚʁɧɨ ɜɢɲɟ ɩɪɟɨɩɟɪɚɬɢɜɧɨ ɭ ɨɞɧɨɫɭ ɧɚ ʃɢɯɨɜɟ ɤɨɧɰɟɧɬɪɚɰɢʁɟ ɩɨɫɥɟ ɨɩɟɪɚɰɢʁɟ  Ʉɨɧɰɟɧɬɪɚɰɢʁɟ KIM-1 ɢ AQP-1 ɭ ɭɪɢɧɭ ɩɚɰɢʁɟɧɚɬɚ ɫɚ ɤɚɪɰɢɧɨɦɨɦ ɫɜɟɬɥɢɯ ʄɟɥɢʁɚ ɛɭɛɪɟɝɚ ɫɭ ɡɧɚɱɚʁɧɨ ɜɢɲɟ ɭ ɩɨɪɟђɟʃɭ ɫɚ ʃɢɯɨɜɢɦ ɤɨɧɰɟɧɬɪɚɰɢʁɚɦɚ ɭ ɭɪɢɧɭ ɡɞɪɚɜɢɯ ɨɫɨɛɚ  Ʉɨɧɰɟɧɬɪɚɰɢʁɟ KIM-1 ɢ AQP-1 ɭ ɭɪɢɧɭ ɩɚɰɢʁɟɧɚɬɚ ɫɚ ɤɚɪɰɢɧɨɦɨɦ ɫɜɟɬɥɢɯ ʄɟɥɢʁɚ ɛɭɛɪɟɝɚ ɫɪɚɡɦɟɪɧɟ ɫɭ TNM ɫɬɚɞɢʁɭɦɭ ɛɨɥɟɫɬɢ ɢ Furhman-ɨɜɨɦ ɝɪɚɞɭɫɭ  Ʉɨɧɰɟɧɬɪɚɰɢʁɚ KIM-1ɭ ɭɪɢɧɭ ɩɚɰɢʁɟɧɚɬɚ ɫɚ ɤɚɪɰɢɧɨɦɨɦ ɫɜɟɬɥɢɯ ʄɟɥɢʁɚ ɛɭɛɪɟɝɚ ɫɪɚɡɦɟɪɧɚ ʁɟ ʃɟɝɨɜɨʁ ɟɤɫɩɪɟɫɢʁɢ ɭ ɬɭɦɨɪɫɤɨɦ ɬɤɢɜɭ  ɉɨɫɬɨɩɟɪɚɬɢɜɧɨ ɨɞɪɠɚɜɚʃɟ ɩɨɜɢɲɟɧɢɯ ɤɨɧɰɟɧɬɪɚɰɢʁɚ KIM-1 ɭ ɭɪɢɧɭ ɩɚɰɢʁɟɧɚɬɚ ɫɚ ɩɚɪɰɢʁɚɥɧɨɦ ɧɟɮɪɟɤɬɨɦɢʁɨɦ ʁɟ ɩɨɫɥɟɞɢɰɚ ɢɫɯɟɦɢʁɫɤɨɝ ɨɲɬɟʄɟʃɚ  ɈɞɪɟђɢɜɚʃɟɤɨɧɰɟɧɬɪɚɰɢʁɟKIM-1 ɭ ɭɪɢɧɭ ɩɚɰɢʁɟɧɚɬɚ ɫɚ ɤɚɪɰɢɧɨɦɨɦ ɫɜɟɬɥɢɯ ʄɟɥɢʁɚ ɛɭɛɪɟɝɚ ɩɪɟɞɫɬɚɜʂɚ ɫɟɧɡɢɬɢɜɚɧ ɚɥɢ ɧɟɞɨɜɨʂɧɨ ɫɩɟɰɢɮɢɱɚɧ ɛɢɨɦɚɪɤɟɪ ɡɚ ɞɢʁɚɝɧɨɡɭ ɛɨɥɟɫɬɢ  Ɉɞɪɟђɢɜɚʃɟɤɨɧɰɟɧɬɪɚɰɢʁɟ AQP-1 ɭ ɭɪɢɧɭ ɩɚɰɢʁɟɧɚɬɚ ɫɚ ɤɚɪɰɢɧɨɦɨɦ ɫɜɟɬɥɢɯ ʄɟɥɢʁɚ ɛɭɛɪɟɝɚ ɩɪɟɞɫɬɚɜʂɚ ɫɟɧɡɢɬɢɜɚɧ ɢ ɫɩɟɰɢɮɢɱɚɧ ɛɢɨɦɚɪɤɟɪ ɡɚ ɞɢʁɚɝɧɨɡɭ ɛɨɥɟɫɬɢ Ɋɚɞɢ ɩɪɨɜɟɪɟ ɪɚɞɧɟ ɯɢɩɨɬɟɡɟ, ɩɨɫɬɚɜɢɥɢ ɫɦɨ ɫɥɟɞɟʄɟ ɰɢʂɟɜɟ ɢɫɬɪɚɠɢɜɚʃɚ:  Ⱥɧɚɥɢɡɢɪɚɬɢɩɚɰɢʁɟɧɬɟ ɩɪɟɦɚ ɩɨɥɭ, ɝɨɞɢɧɚɦɚɠɢɜɨɬɚ, ɢɧɞɟɤɫɭ ɬɟɥɟɫɧɟ ɦɚɫɟ (ȻɆɂ), ɧɚɜɢɤɚɦɚ ɭ ɩɭɲɟʃɭ, ɛɭɛɪɟɠɧɨʁ ɮɭɧɤɰɢʁɢ ɢ ɩɪɢɫɭɫɬɜɭ ɫɢɦɩɬɨɦɚ ɩɚɪɚɧɟɨɩɥɚɫɬɢɱɧɨɝ ɫɢɧɞɪɨɦɚ  Ɉɞɪɟɞɢɬɢ ɤɨɧɰɟɧɬɪɚɰɢʁɟ KIM-1 ɢ AQP-1 ɭ ɭɪɢɧɭ ɩɚɰɢʁɟɧɚɬɚ ɫɚ ɤɚɪɰɢɧɨɦɨɦ ɫɜɟɬɥɢɯ ʄɟɥɢʁɚ ɛɭɛɪɟɝɚ ɧɚ ɞɚɧ ɨɩɟɪɚɬɢɜɧɨɝ ɥɟɱɟʃɚ, 7. ɢ 30. ɞɚɧɚɧɚɤɨɧ ɨɩɟɪɚɰɢʁɟ  Ʉɨɪɟɥɢɪɚɬɢ ɤɨɧɰɟɧɬɪɚɰɢʁɭ KIM-ɢ AQP-1 ɭ ɭɪɢɧɭ ɩɚɰɢʁɟɧɚɬɚ ɫɚ ɤɚɪɰɢɧɨɦɨɦ ɫɜɟɬɥɢɯ ʄɟɥɢʁɚ ɛɭɛɪɟɝɚ ɩɪɟ ɢ ɩɨɫɬɨɩɟɪɚɬɢɜɧɨ ɫɚ ʃɢɯɨɜɢɦ ɤɨɧɰɟɧɬɪɚɰɢʁɚɦɚ ɭ ɭɪɢɧɭ ɡɞɪɚɜɢɯ ɨɫɨɛɚ  Ʉɨɪɟɥɢɪɚɬɢ ɤɨɧɰɟɧɬɪɚɰɢʁɭ KIM-1 ɢ AQP-1 ɭ ɭɪɢɧɭ ɩɚɰɢʁɟɧɚɬɚ ɫɚ ɤɚɪɰɢɧɨɦɨɦ ɫɜɟɬɥɢɯ ʄɟɥɢʁɚ ɛɭɛɪɟɝɚ ɧɚ ɞɚɧ ɨɩɟɪɚɬɢɜɧɨɝ ɥɟɱɟʃɚ ɫɚ ɜɟɥɢɱɢɧɨɦ, ɝɪɚɞɭɫɨɦ, pT, TNM ɫɬɚɞɢʁɭɦɨɦ ɛɨɥɟɫɬɢ ɢ ɥɢɦɮɧɨ-ɜɚɫɤɭɥɚɪɧɨɦ ɢɧɜɚɡɢʁɨɦ  Ʉɨɪɟɥɢɪɚɬɢ ɩɪɟɨɩɟɪɚɬɢɜɧɟ ɢ ɩɨɫɬɨɩɟɪɚɬɢɜɧɟ ɤɨɧɰɟɧɬɪɚɰɢʁɟ KIM-1 ɢ AQP-1 ɭ ɭɪɢɧɭ ɩɚɰɢʁɟɧɚɬɚ ɫɚ ɤɚɪɰɢɧɨɦɨɦ ɫɜɟɬɥɢɯ ʄɟɥɢʁɚ ɛɭɛɪɟɝɚ ɭ ɡɚɜɢɫɧɨɫɬɢ ɨɞ ɬɢɩɚ ɨɩɟɪɚɬɢɜɧɨɝ ɥɟɱɟʃɚ, ɩɚɪɰɢʁɚɥɧɚ ɢɥɢ ɪɚɞɢɤɚɥɧɚ ɧɟɮɪɟɤɬɨɦɢʁɚ  Ʉɨɪɟɥɢɪɚɬɢ ɤɨɧɰɟɧɬɪɚɰɢʁɭ KIM-1 ɭ ɭɪɢɧɭ ɩɚɰɢʁɟɧɚɬɚ ɫɚ ɤɚɪɰɢɧɨɦɨɦ ɫɜɟɬɥɢɯ ʄɟɥɢʁɚ ɛɭɛɪɟɝɚ ɧɚ ɞɚɧ ɨɩɟɪɚɬɢɜɧɨɝ ɥɟɱɟʃɚ ɫɚ ɟɤɫɩɪɟɫɢʁɨɦ KIM-1 ɭ ɬɭɦɨɪɫɤɨɦ ɬɤɢɜɭ ɏɂɉɈɌȿɁȿ ɂ ɐɂȴȿȼɂ ɂɋɌɊȺɀɂȼȺȵȺ 28  Ʉɨɪɟɥɢɪɚɬɢ ɟɤɫɩɪɟɫɢʁɭ KIM-1 ɭ ɬɭɦɨɪɫɤɨɦ ɬɤɢɜɭ ɫɚ ɜɟɥɢɱɢɧɨɦ, ɝɪɚɞɭɫɨɦ, pT, TNM ɫɬɚɞɢʁɭɦɨɦ ɛɨɥɟɫɬɢ ɢ ɥɢɦɮɧɨ-ɜɚɫɤɭɥɚɪɧɨɦ ɢɧɜɚɡɢʁɨɦ  Ɉɞɪɟɞɢɬɢ ɞɢʁɚɝɧɨɫɬɢɱɤɢ ɩɨɬɟɧɰɢʁɚɥ ɭɪɢɧɚɪɧɟ ɤɨɧɰɟɧɬɪɚɰɢʁɟ KIM-1 ɢ AQP-1 ɡɚ ɞɢʁɚɝɧɨɡɭ ɤɚɪɰɢɧɨɦɚ ɫɜɟɬɥɢɯ ʄɟɥɢʁɚ ɛɭɛɪɟɝɚ ɆȺɌȿɊɂȳȺɅ ɂ ɆȿɌɈȾȿ 29 3. ɆȺɌȿɊɂȳȺɅ ɂ ɆȿɌɈȾȿ 3.1. ɉɨɞɚɰɢ ɨ ɢɫɩɢɬɚɧɢɰɢɦɚ ɢ ɚɧɚɥɢɡɢɪɚɧɢɦ ɭɡɨɪɰɢɦɚ 3.1.1. Ʉɥɢɧɢɱɤɟ ɤɚɪɚɤɬɟɪɢɫɬɢɤɟ ɝɪɭɩɟ ɨɛɨɥɟɥɢɯ ɂɫɬɪɚɠɢɜɚʃɟɦ ʁɟ ɨɛɭɯɜɚʄɟɧ 41 ɩɚɰɢʁɟɧɬ ɫɚ ɭɥɬɪɚɡɜɭɱɧɨ ɢ ɦɭɥɬɢɫɥɚʁɫɧɢɦ ɫɤɟɧɟɪɫɤɢɦ ɩɪɟɝɥɟɞɨɦ ɚɛɞɨɦɟɧɚ (MSCT) ɞɢʁɚɝɧɨɫɬɢɤɨɜɚɧɨɦ ɬɭɦɨɪɫɤɨɦ ɩɪɨɦɟɧɨɦ ɧɚ ɛɭɛɪɟɝɭ ɢ ɩɨɫɬɚɜʂɟɧɨɦ ɢɧɞɢɤɚɰɢʁɨɦ ɡɚ ɨɩɟɪɚɬɢɜɧɨ ɥɟɱɟʃɟ. ɋɜɢ ɩɚɰɢʁɟɧɝɬɢ ɫɭ ɨɩɟɪɚɬɢɜɧɨ ɥɟɱɟɧɢ ɩɪɢɦɟɧɨɦ ɨɬɜɨɪɟɧɟ ɬɪɚɧɫɥɭɦɛɚɥɧɟ ɪɚɞɢɤɚɥɧɟ ɢɥɢ ɩɚɪɰɢʁɚɥɧɟ ɧɟɮɪɟɤɬɨɦɢʁɟ ɭ Ʉɥɢɧɢɰɢ ɡɚ ɭɪɨɥɨɝɢʁɭ ȼɆȺ ɭ ɩɟɪɢɨɞɭ ɨɞ ɦɚʁɚ 2012. ɞɨ ɫɟɩɬɟɦɛɪɚ 2013. Ʉɨɞ ɫɜɢɯ ɩɚɰɢʁɟɧɚɬɚ ʁɟ ɭ ɂɧɫɬɢɬɭɬɭ ɡɚ ɩɚɬɨɥɨɝɢʁɭ ȼɆȺ ɩɚɬɨɯɢɫɬɨɥɨɲɤɨɦ ɚɧɚɥɢɡɨɦ ɨɞɫɬɪɚʃɟɧɨɝ ɬɭɦɨɪɫɤɨɝ ɬɤɢɜɚ ɞɢʁɚɝɧɨɫɬɢɤɨɜɚɧ ɤɚɪɰɢɧɨɦ ɫɜɟɬɥɢɯ ʄɟɥɢʁɚ ɛɭɛɪɟɝɚ ɢ ɨɞɪɟђɟɧ ɩɚɬɨɯɢɫɬɨɥɨɲɤɢ ɫɬɚɞɢʁɭɦ ɬɭɦɨɪɚ ɩɪɟɦɚ ɫɟɞɦɨʁ TNM ɦɟђɭɧɚɪɨɞɧɨʁ ɤɥɚɫɢɮɢɤɚɰɢʁɢ ɤɚɪɰɢɧɨɦɚ ɛɭɛɪɟɝɚ180. Ʉɨɧɬɪɨɥɧɭ ɝɪɭɩɭ ɱɢɧɢɥɨ ʁɟ 40 ɡɞɪɚɜɢɯ ɢɫɩɢɬɚɧɢɤɚ. ɇɢʁɟ ɛɢɥɨ ɫɬɚɬɢɫɬɢɱɤɢ ɡɧɚɱɚʁɧɟ ɪɚɡɥɢɤɟ ɢɡɦɟђɭ ɝɪɭɩɚ ɩɪɟɦɚ ɩɨɥɭ, ɝɨɞɢɧɚɦɚ ɠɢɜɨɬɚ ɢ ɛɭɛɪɟɠɧɨʁ ɮɭɧɤɰɢʁɢ. Ɍɨɤɨɦ ɢɫɬɪɚɠɢɜɚʃɚ ɤɨɞ ɫɜɢɯ ɢɫɩɢɬɚɧɢɤɚ ɭ ɝɪɭɩɢ ɨɛɨɥɟɥɢɯ ɨɞɪɟђɟɧɨ ʁɟ ɫɥɟɞɟʄɟ:  Ɉɫɧɨɜɧɢ ɩɨɞɚɰɢ ɨ ɩɚɰɢʁɟɧɬɢɦɚ: ɩɨɥ, ɠɢɜɨɬɧɚ ɞɨɛ, ɬɟɥɟɫɧɚ ɦɚɫɚ, ɬɟɥɟɫɧɚ ɜɢɫɢɧɚ ɢ ɢɧɞɟɤɫ ɬɟɥɟɫɧɟ ɦɚɫɟ (ɟɧɝɥ. ɫɤɪ. BMI-body mass index). ɂɧɞɟɤɫ ɬɟɥɟɫɧɟ ɦɚɫɟ ʁɟ ɨɞɪɟђɟɧ ɩɪɟɦɚ ɮɨɪɦɭɥɢ: ɬɟɥɟɫɧɚ ɬɟɠɢɧɚ /(ɬɟɥɟɫɧɚ ɜɢɫɢɧɚ)2 ɢ ɢɡɪɚɠɟɧɨ ɭ kg/m2. ɉɚɰɢʁɟɧɬɢ ɫɭ ɩɪɟɦɚ ɜɪɟɞɧɨɫɬɢ BMI ɩɨɞɟʂɟɧɢ ɭ 4 ɝɪɭɩɟ: 1. ɩɨɬɯɪɚʃɟɧɢ (BMI< 18,5), 2. ɧɨɪɦɚɥɧɨ ɭɯɪɚʃɟɧɢ (BMI 18,5-24,9), 3. ɭɦɟɪɟɧɨ ɝɨʁɚɡɧɢ (BMI 25-29,9) 4. ɝɨʁɚɡɧɢ (BMI≥30).  Ⱥɧɚɦɧɟɫɬɢɱɤɢ ɢ ɩɨɞɚɰɢ ɢɡ ɢɫɬɨɪɢʁɟ ɛɨɥɟɫɬɢ ɨ ɩɨɫɬɨʁɚʃɭ ɚɤɭɬɧɢɯ ɢɥɢ ɯɪɨɧɢɱɧɢɯ ɛɭɛɪɟɠɧɢɯ ɛɨɥɟɫɬɢ, ɚɪɬɟɪɢʁɫɤɟ ɯɢɩɟɪɬɟɧɡɢʁɟ, ɲɟʄɟɪɧɟ ɛɨɥɟɫɬɢ, ɧɚɜɢɤɚ ɭ ɩɭɲɟʃɭ ɢ ɩɨɫɬɨʁɚʃɭ ɩɨɪɨɞɢɱɧɨɝ ɨɩɬɟɪɟʄɟʃɚ ɡɚ ɬɭɦɨɪ ɛɭɛɪɟɝɚ.  Ⱥɧɚɦɧɟɫɬɢɱɤɢ ɩɨɞɚɰɢ ɨ ɩɪɢɫɭɫɬɜɭ/ɨɞɫɭɫɬɜɭ ɫɢɦɩɬɨɦɚ ɢ ɡɧɚɤɨɜɚ ɩɚɪɚɧɟɨɩɥɚɫɬɢɱɤɨɝ ɫɢɧɞɪɨɦɚ: ɥɭɦɛɚɥɧɢ ɛɨɥ, ɦɚɤɪɨɫɤɨɩɫɤɚ ɯɟɦɚɬɭɪɢʁɚ, ɝɭɛɢɬɚɤ ɭ ɬɟɥɟɫɧɨʁ ɦɚɫɢ, ɩɨɜɢɲɟɧɚ ɬɟɥɟɫɧɚ ɬɟɦɟɩɟɪɚɬɭɪɚ.  ɍɡɨɪɚɤ ɤɪɜɢ ɡɚ ɨɞɪɟђɢɜɚʃɟ ɨɫɧɨɜɧɨɝ ɯɟɦɚɬɨɥɨɲɤɨɝ ɢ ɛɢɨɯɟɦɢʁɫɤɨɝ ɩɪɨɮɢɥɚ: ɤɨɦɩɥɟɬɧɚ ɤɪɜɧɚ ɫɥɢɤɚ, ɭɪɟɚ, ɤɪɟɚɬɢɧɢɧ, ɝɥɢɤɟɦɢʁɚ, ɚɥɛɭɦɢɧɢ, ɤɚɥɢʁɭɦ, ɤɚɥɰɢʁɭɦ  ɍɥɬɪɚɡɜɭɱɧɢ ɩɪɟɝɥɟɞ ɚɛɞɨɦɟɧɚ ɢ ɦɭɥɬɢɫɥɚʁɫɧɢ ɫɤɟɧɟɪɫɤɢ ɩɪɟɝɥɟɞ ɚɛɞɨɦɟɧɚ ɢ ɝɪɭɞɧɨɝ ɤɨɲɚ ɪɚɞɢ ɨɞɪɟђɢɜɚʃɚ ɜɟɥɢɱɢɧɟ ɬɭɦɨɪɚ ɢ ɨɞɫɭɫɬɜɨ/ɩɪɢɫɭɫɬɜɨ ɥɨɤɚɥɧɢɯ ɢ ɭɞɚʂɟɧɢɯ ɦɟɬɚɫɬɚɬɫɤɢɯ ɩɪɨɦɟɧɚ.  Ɉɞɪɟђɟɧ ʁɟ ɤɥɢɪɟɧɫ ɤɪɟɚɬɢɧɢɧɚ ɩɪɢɦɟɧɨɦ CKD-EPI ɮɨɪɦɭɥɟ: (GFR = 141 × min(Scr /κ, 1)α× max(Scr /κ, 1)-1.209 × 0.993ɠ. ɞɨɛ × 1.018 [ɚɤɨ ʁɟ ɨɫɨɛɚ ɠɟɧɫɤɨɝ ɩɨɥɚ]) ɢ ɢɡɪɚɠɟɧ ɭ ml/min/1,73 m2187. ɆȺɌȿɊɂȳȺɅ ɂ ɆȿɌɈȾȿ 30  ɍɡɟɬ ʁɟ ɭɡɨɪɚɤ ɩɪɜɨɝ ʁɭɬɚɪʃɟɝ ɭɪɢɧɚ ɩɪɟ ɨɩɟɪɚɰɢʁɟ, 7. ɢ 30. ɞɚɧɚ ɧɚɤɨɧ ɨɩɟɪɚɰɢʁɟ ɢ ɭ ɪɨɤɭ ɨɞ 4 ɫɚɬɚ ɨɞ ɬɪɟɧɭɬɤɚ ɭɡɢɦɚʃɚ ɡɚɦɪɡɧɭɬ ɧɚ -80°C ɪɚɞɢ ɨɞɪɟђɢɜɚʃɚ ɤɨɧɰɟɧɬɪɚɰɢʁɟ ɤɪɟɚɬɢɧɢɧɚ, KIM-1ɢ AQP-1.  Ɉɞɪɟђɟɧ ʁɟ ɫɬɚɞɢʁɭɦ ɛɨɥɟɫɬɢ ɩɪɟɦɚTNM ɤɥɚɫɢɮɢɤɚɰɢʁɢ ɬɭɦɨɪɚ ɛɭɛɪɟɝɚ ɢɡ 2010. ɝɨɞɢɧɟ180.  Ɉɞɪɟђɟɧ ʁɟ ɧɭɤɥɟɚɪɧɢ ɝɪɚɞɭɫ ɬɭɦɨɪɚ ɩɪɟɦɚ Furhmanov-ɨʁ ɤɥɚɫɢɮɢɤɚɰɢʁɢ ɤɚɪɰɢɧɨɦɚ ɛɭɛɪɟɝɚ182.  ɍɬɜɪђɟɧɚ ʁɟ ɢɦɭɧɨɯɢɫɬɨɯɟɦɢʁɫɤɚ ɟɤɫɩɪɟɫɢʁɚ KIM-1 ɭ ɬɭɦɨɪɫɤɨɦ ɬɤɢɜɭ ɍɤʂɭɱɭʁɭʄɢ ɤɪɢɬɟɪɢʁɭɦɢ ɡɚ ɢɫɩɢɬɢɜɚʃɟ ɛɢɥɢ ɫɭ: 1. ɩɚɬɨɯɢɫɬɨɥɨɲɤɢ ɩɨɫɬɚɜʂɟɧɚ ɞɢʁɚɝɧɨɡɚ ɤɚɪɰɢɧɨɦɚ ɫɜɟɬɥɢɯ ʄɟɥɢʁɚ ɛɭɛɪɟɝɚ 2. ɩɨɬɩɢɫɚɧ ɮɨɪɦɭɥɚɪ ɢɧɮɨɪɦɢɫɚɧɨɝ ɩɪɢɫɬɚɧɤɚ ɂɫɤʂɭɱɭʁɭʄɢ ɤɪɢɬɟɪɢʁɭɦɢ ɡɚ ɢɫɩɢɬɢɜɚʃɟ ɫɭ ɛɢɥɢ: 1. ɤɥɢɪɟɧɫ ɤɪɟɚɬɢɧɢɧɚ ɦɚʃɢɨɞ 60 ml/min/1,73 m2 ɢɡɪɚɱɭɧɚɬɢ ɩɪɢɦɟɧɨɦ CKD-EPI ɮɨɪɦɭɥɟ 2. ɩɨɞɚɬɚɤ ɞɚ ɫɟ ɩɚɰɢʁɟɧɬ ɥɟɱɢ ɢɥɢ ʁɟ ɪɚɧɢʁɟ ɥɟɱɟɧ ɨɞ ɧɟɤɨɝ ɛɭɛɪɟɠɧɨɝ ɨɛɨʂɟʃɚ ɢ ɦɚɥɢɝɧɟ ɛɨɥɟɫɬɢ 3. ɩɨɞɚɬɚɤ ɞɚ ɩɚɰɢʁɟɧɬ ɛɨɥɭʁɟ ɨɞ ɲɟʄɟɪɧɟ ɛɨɥɟɫɬɢ ɬɢɩ 1 ɢɥɢ 2 4. ɩɨɞɚɬɚɤ ɞɚ ʁɟ ɩɚɰɢʁɟɧɬ 10 ɞɚɧɚ ɢ ɤɪɚʄɟ ɩɪɟ ɭɡɢɦɚʃɚ ɭɡɨɪɤɚ ɭɪɢɧɚ ɡɚ KIM-1 ɢ AQP-1 ɢɦɚɨ ɤɨɧɬɪɚɫɬɧɨ ɫɧɢɦɚʃɟ 5. ɩɚɰɢʁɟɧɬɤɢʃɟ ɤɨʁɟ ɭ ɢɫɬɨɪɢʁɢ ɛɨɥɟɫɬɢ ɢɦɚʁɭ ɩɨɞɚɬɚɤ ɞɚ ɫɭ ɥɟɱɟɧɟ ɨɞ ɤɚɪɰɢɧɨɦɚ ɫɜɟɬɥɢɯ ʄɟɥɢʁɚ ʁɚʁɧɢɤɚ 6. ɩɨɜɪɟɞɚ ɩɪɨɬɨɤɨɥɚ ɫɬɭɞɢʁɟ. 3.1.2. Ʉɥɢɧɢɱɤɟ ɤɚɪɚɤɬɟɪɢɫɬɢɤɟ ɤɨɧɬɪɨɥɧɟ ɝɪɭɩɟ Ʉɨɧɬɪɨɥɧɭ ɝɪɭɩɭ ɱɢɧɢɥɨ ʁɟ 40 ɨɞɪɚɫɥɢɯ, ɡɞɪɚɜɢɯ ɨɫɨɛɚ, ɤɨʁɢ ɫɭ ɩɨɬɩɢɫɚɥɢ ɢɧɮɨɪɦɢɫɚɧɢ ɩɪɢɫɬɚɧɚɤ ɡɚ ɭɱɟɲʄɟ ɭ ɫɬɭɞɢʁɢ. Ɉɞ ɫɜɢɯ ɨɫɨɛɚ ɭɡɟɬ ʁɟ ʁɟɞɚɧ ɭɡɨɪɚɤ ɤɪɜɢ ɡɚ ɨɞɪɟђɢɜɚʃɟ ɭɪɟɟ, ɤɪɟɚɬɢɧɢɧɚ, ɝɥɢɤɟɦɢʁɟ, ɚɥɛɭɦɢɧɚ, ɤɚɥɢʁɭɦɚ ɢ ɤɚɥɰɢʁɭɦɚ ɢ ʁɟɞɚɧ ɭɡɨɪɚɤ ɭɪɢɧɚ ɡɚ ɨɞɪɟђɢɜɚʃɟ KIM-1, AQP-1 ɢ ɤɪɟɚɬɢɧɢɧɚ. 3.1.3.Ɉɞɪɟђɢɜɚʃɟ ɤɨɧɰɟɧɬɪɚɰɢʁɟ KIM-1 ɭ ɭɪɢɧɭ Ɂɚ ɨɞɪɟђɢɜɚʃɟ ɤɨɧɰɟɧɬɪɚɰɢʁɟ KIM-1,ɤɨɞ ɫɜɢɯ ɩɚɰɢʁɟɧɚɬɚ ʁɟ ɩɪɟ ɨɩɟɪɚɰɢʁɟ, 7. ɢ 30. ɞɚɧɚ ɧɚɤɨɧ ɨɩɟɪɚɰɢʁɟ ɭɡɟɬ ɭɡɨɪɚɤ ɩɪɜɨɝ ʁɭɬɚɪʃɟɝ ɭɪɢɧɚ, ɢɫɰɟɧɬɪɢɮɭɝɢɪɚɧ ɧɚ 1800 g ɭ ɬɪɚʁɚʃɭ ɨɞ 10 ɦɢɧɭɬɚ ɢ ɨɞɫɬɪɚʃɟɧ ɬɚɥɨɝ. Ɍɟɱɧɢ ɞɟɨ ʁɟ ɨɞɥɢɜɟɧ ɭ ɟɩɟɧɞɨɪɮɟ ɡɚɩɪɟɦɢɧɟ 1,5 ml ɢ ɞɨɦɨɦɟɧɬɚɚɧɚɥɢɡɟɡɚɦɪɡɧɭɬɧɚ -80°C. Ʉɨɧɰɟɧɬɪɚɰɢʁɚ KIM-1ɨɞɪɟђɟɧɚʁɟ ɩɪɢɦɟɧɨɦELISA ɤɨɦɟɪɰɢʁɚɥɧɨɝɢɦɭɧɨɟɧɡɢɦɫɤɨɝɬɟɫɬɚ (ELISA, TIM-1/KIM-1/HAVCR, R&D Systems Inc, Minneapolis, MN, USA). Ⱦɨɛɢʁɟɧɟ ɜɪɟɞɧɨɫɬɢ ɫɭ ɢɡɪɚɠɟɧɟ ɭ ɚɩɫɨɥɭɬɧɨʁ ɤɨɧɰɟɧɬɪɚɰɢʁɢ ɆȺɌȿɊɂȳȺɅ ɂ ɆȿɌɈȾȿ 31 (ng/ml) ɢ ɤɨɪɢɝɨɜɚɧɨʁ ɩɪɟɦɚ ɤɨɧɰɟɧɬɪɚɰɢʁɢ ɤɪɟɚɬɢɧɢɧɚ ɭ ɞɚɬɨɦ ɭɡɨɪɤɭ ɭɪɢɧɚ ɢ ɢɡɪɚɠɟɧɟ ɭ ng/mgUCr. Ʉɨɧɰɟɧɬɪɚɰɢʁɚ ɤɪɟɚɬɢɧɢɧɚ ɭ ɭɪɢɧɭ ʁɟ ɨɞɪɟђɟɧɚ ɦɨɞɢɮɢɤɨɜɚɧɨɦ Jaffe ɦɟɬɨɞɨɦ188.Ɍɟɫɬ ɫɟ ɡɚɫɧɢɜɚ ɧɚ ɤɜɚɧɬɢɬɚɬɢɜɧɨʁ ɫɟɧɞɜɢɱ ɟɧɡɢɦ ɢɦɭɧɨɟɫɟʁ ɬɟɯɧɢɰɢ. ɍ ɬɟɫɬɭ ɫɭ ɤɨɪɢɲʄɟɧɟ ɩɨɥɢɫɬɢɪɟɧɫɤɟ ɩɥɨɱɟ ɫɚ 96 ɛɭɧɚɪɱɢʄɚ. Ⱦɧɨ ɫɜɚɤɨɝ ɛɭɧɚɪɱɢʄɚ ʁɟ ɨɛɥɨɠɟɧɨ ɦɢɲɢʁɢɦ ɦɨɧɨɤɥɨɧɫɤɢɦ ɚɧɬɢɬɟɥɢɦɚ ɫɩɟɰɢɮɢɱɧɢɦ ɡɚ KIM-1. ɉɪɜɨ ʁɟ ɞɨɞɚɬ Ⱦɢɥɭɟɧɬ RD1- 82 ɭ ɫɜɚɤɢ ɛɭɧɚɪɱɢʄ ɦɢɤɪɨɩɥɨɱɟ, ɚ ɡɚɬɢɦ ɪɟɤɨɦɛɢɧɚɧɬɧɢ ɯɭɦɚɧɢ KIM-1 ɢ ɭɡɨɪɰɢ ɭɪɢɧɚ. ɉɪɢɫɭɬɧɢ KIM-1 ʁɟ ɜɟɡɚɧ ɢɦɨɛɢɥɢɡɢɪɚɧɢɦ ɚɧɬɢɬɟɥɢɦɚ. ɇɚɤɨɧ ɢɫɩɢɪɚʃɚ, ɭ ɫɜɚɤɢ ɩɪɨɫɬɨɪ ɦɢɤɪɨɩɥɨɱɟ ɞɨɞɚɬ ʁɟ ɤɨʃɭɝɚɬ ɤɨɝɚ ɫɭ ɱɢɧɢɥɚ ɩɨɥɢɤɥɨɧɫɤɚ ɚɧɬɢɬɟɥɚ ɜɟɡɚɧɚ ɡɚ ɩɟɪɨɤɫɢɞɚɡɭ ɪɟɧɚ ɫɩɟɰɢɮɢɱɧɭ ɩɪɟɦɚ KIM-1. ɉɨɫɬɭɩɚɤ ɢɫɩɢɪɚʃɚ ʁɟ ɩɨɧɨɜʂɟɧ ɢ ɞɨɞɚɬ ʁɟ ɫɭɩɫɬɪɚɬ. ɂɧɬɟɡɢɬɟɬ ɪɚɡɜɢʁɟɧɟ ɛɨʁɟ ɛɢɨ ʁɟ ɩɪɨɩɨɪɰɢɨɧɚɥɚɧ ɤɨɥɢɱɢɧɢ ɜɟɡɚɧɨɝ KIM-1ɭ ɩɪɜɨɦ ɤɨɪɚɤɭ. Ɋɟɚɤɰɢʁɚ ʁɟ ɩɪɟɤɢɧɭɬɚ ɞɨɞɚɜɚʃɟɦ ɪɚɫɬɜɨɪɚ ɡɚ ɫɬɨɩɢɪɚʃɟ. Ɇɢɧɢɦɚɥɧɚ ɤɨɧɰɟɧɬɪɚɰɢʁɚ KIM- 1ɤɨʁɚ ʁɟ ɦɨɝɥɚ ɛɢɬɢ ɞɟɬɟɤɬɨɜɚɧɚ ɭ ɭɪɢɧɭ ɩɪɢɦɟɧɨɦ ɨɜɨɝ ɬɟɫɬɚ ɢɡɧɨɫɢɥɚ ʁɟ 0,003-0,046 ng/ml. Ⱥɛɫɨɪɛɚɧɰɚ ʁɟ ɦɟɪɟɧɚ ɧɚ ɫɩɟɤɬɪɨɮɨɬɨɦɟɬɪɭ, ɧɚ ɬɚɥɚɫɧɨʁ ɞɭɠɢɧɢ ɨɞ 450 nmɭ ɬɪɚʁɚʃɭ ɨɞ 30 ɦɢɧɭɬɚ. Ʉɨɧɰɟɧɬɪɚɰɢʁɚ KIM-1 ʁɟ ɭ ɫɜɚɤɨɦ ɭɡɨɪɤɭ ɢɫɤɚɡɚɧɚ ɭ ɚɩɫɨɥɭɬɧɨʁ ɤɨɧɰɟɧɬɪɚɰɢʁɢ (ng/ml) ɢ ɤɨɪɢɝɨɜɚɧɨʁ ɤɨɧɰɟɧɬɪɚɰɢʁɢ ɩɪɟɦɚ ɜɪɟɞɧɨɫɬɢ ɤɪɟɚɬɢɧɢɧɚ ɭ ɞɚɬɨɦ ɭɡɨɪɤɭ ɭɪɢɧɚ ɢ ɢɫɤɚɡɚɧɚ ɭ ng/mgUCr. Ʉɨɧɰɟɧɬɪɚɰɢʁɚ ɤɪɟɚɬɢɧɢɧɚ ɭ ɭɪɢɧɭ ʁɟ ɨɞɪɟђɟɧɚ ɦɨɞɢɮɢɤɨɜɚɧɨɦ Jaffe ɦɟɬɨɞɨɦ188. 3.1.4. Ɉɞɪɟђɢɜɚʃɟ ɤɨɧɰɟɧɬɪɚɰɢʁɟ AQP-1 ɭ ɭɪɢɧɭ Ⱥɧɚɥɢɡɚ ʁɟ ɪɚђɟɧɚ ɧɚ ɩɪɟɞɯɨɞɧɨ ɭɡɟɬɢɦ ɭɡɨɪɰɢɦɚ ɭɪɢɧɚ ɤɨʁɢ ɫɭ ɞɨ ɦɨɦɟɧɬɚ ɚɧɚɥɢɡɟ ɛɢɥɢ ɡɚɦɪɡɧɭɬɢ ɧɚ -80°C. Ⱥɤɜɚɩɨɪɢɧ 1 ʁɟ ɨɞɪɟђɟɧ ɩɪɢɦɟɧɨɦ ELISA ɤɨɦɟɪɰɢʁɚɥɧɨɝ ɢɦɭɧɨɟɧɡɢɦɫɤɨɝ ɬɟɫɬɚ (AQP1 (Human) ELISA Kit, Abnova, Heidelberg, Germany). Ɍɟɫɬ ʁɟ ɡɚɫɧɨɜɚɧ ɧɚ ɤɜɚɧɬɢɬɚɬɢɜɧɨʁ ɫɟɧɞɜɢɱ ɟɧɡɢɦ ɢɦɭɧɨɟɫɟʁ ɬɟɯɧɢɰɢ. ɍ ɬɟɫɬɭ ɫɭ ɤɨɪɢɲʄɟɧɟ ɩɨɥɢɫɬɢɪɟɧɫɤɟ ɩɥɨɱɟ ɫɚ 96 ɛɭɧɚɪɱɢʄɚ. Ⱦɧɨ ɫɜɚɤɨɝɛɭɧɚɪɱɢʄɚ ɨɛɥɨɠɟɧɨ ʁɟ ɚɧɬɢɬɟɥɢɦɚ ɫɩɟɰɢɮɢɱɧɢɦ ɡɚ AQP-1. ɍ ɫɜɚɤɢ ɛɭɧɚɪɱɢʄ ɦɢɤɪɨɩɥɨɱɟ ɨɛɥɨɠɟɧ ɛɢɨɬɢɧ-ɤɨʃɭɝɨɜɚɧɢɦ ɩɨɥɢɤɥɨɧɫɤɢɦ ɚɧɬɢɬɟɥɢɦɚ ɫɩɟɰɢɮɢɱɧɢɦ ɡɚ AQP-1 ɢ Ⱥɜɢɞɢɧɨɦ ɤɨʁɢ ʁɟ ɤɨʃɭɝɨɜɚɧ ɫɚ ɩɟɪɨɤɫɢɞɚɡɨɦ ɪɟɧɚ, ɞɨɞɚɬ ʁɟ ɭɡɨɪɚɤ ɭɪɢɧɚ. ɉɪɢɫɭɫɬɜɨ AQP-1 ɭ ɭɡɨɪɤɭ ɭɪɢɧɚ ɢɡɚɡɜɚɥɨ ʁɟ ɩɪɨɦɟɧɭ ɛɨʁɟ. ȿɧɡɢɦ-ɫɭɩɫɬɪɚɬ ɪɟɚɤɰɢʁɚ ʁɟ ɩɪɟɤɢɧɭɬɚ ɞɨɞɚɜɚʃɟɦ ɪɚɫɬɜɨɪɚ ɫɭɦɩɨɪɧɟ ɤɢɫɟɥɢɧɟ, ɚ ɩɪɨɦɟɧɚ ɛɨʁɟ ʁɟ ɦɟɪɟɧɚ ɫɩɟɤɬɪɨɮɨɬɨɦɟɬɪɢʁɫɤɢ ɧɚ ɬɚɥɚɫɧɨʁ ɞɭɠɢɧɢ ɨɞ 450 nm. Ɇɢɧɢɦɚɥɧɚ ɤɨɧɰɟɧɬɪɚɰɢʁɚ AQP-1 ɤɨʁɚ ɫɟ ɦɨɝɥɚ ɞɟɬɟɤɬɨɜɚɬɢ ɭ ɭɪɢɧɭ ɩɪɢɦɟɧɨɦ ɨɜɨɝ ɬɟɫɬɚ ɢɡɧɨɫɢɥɚ ʁɟ 0,04 ng/ml. Ʉɨɧɰɟɧɬɪɚɰɢʁɚ AQP-1 ʁɟ ɭ ɫɜɚɤɨɦ ɭɡɨɪɤɭ ɢɫɤɚɡɚɧɚ ɭ ɚɩɫɨɥɭɬɧɨʁ ɤɨɧɰɟɧɬɪɚɰɢʁɢ (ng/ml) ɢ ɤɨɪɢɝɨɜɚɧɨʁ ɤɨɧɰɟɧɬɪɚɰɢʁɢ ɩɪɟɦɚ ɜɪɟɞɧɨɫɬɢ ɤɪɟɚɬɢɧɢɧɚ ɭ ɞɚɬɨɦ ɭɡɨɪɤɭ ɭɪɢɧɚ ɢ ɢɫɤɚɡɚɧɚ ɭ ng/mgUCr. 3.1.5. Ɉɞɪɟђɢɜɚʃɟ ɤɪɜɧɟ ɫɥɢɤɟ ɢ ɛɢɨɯɟɦɢʁɫɤɢɯ ɩɚɪɚɦɟɬɚɪɚ ɤɪɜɢ Ʉɪɜɧɚ ɫɥɢɤɚ ɉɚɪɚɦɟɬɪɢ ɤɪɜɧɟ ɫɥɢɤɟ ɫɭ ɚɧɚɥɢɡɢɪɚɧɢ ɢɡ ɜɚɤɭɬɚʁɧɟɪɚ ɫɚ ʂɭɛɢɱɚɫɬɨɦ ɛɨʁɨɦ ɱɟɩɚ (ɩɭɧɚ ɤɪɜ), ɤɨʁɢ ɤɚɨ ɚɬɢɤɨɚɝɭɥɚɧɫ ɫɚɞɪɠɟ Ʉ2ȿȾɌȺ (1,8 ɦɝ Ʉ2ȿȾɌȺ ɩɨml ɤɪɜɢ). Ʉɪɜɧɚ ɫɥɢɤɚ ʁɟ ɨɞɪɟђɟɧɚ ɦɟɬɨɞɨɦ ɩɪɨɬɨɱɧɟ ɰɢɬɨɦɟɬɪɢʁɟ (flow cytometry) ɡɚ ʄɟɥɢʁɫɤɟ ɟɥɟɦɟɧɬɟ, ɞɨɤ ʁɟ ɆȺɌȿɊɂȳȺɅ ɂ ɆȿɌɈȾȿ 32 ɯɟɦɨɝɥɨɛɢɧ ɨɞɪɟђɟɧ ɮɨɬɨɦɟɬɪɢʁɫɤɢ. ɂɫɩɢɬɢɜɚʃɟ ʁɟ ɜɪɲɟɧɨ ɧɚ ɯɟɦɚɬɨɥɨɲɤɨɦ ɛɪɨʁɚɱɭ AНvТК 120, ɩɪɨɢɡɜɨђɚɱɚ Siemens. Ɋɟɮɟɪɟɧɬɧɚ ɜɪɟɞɧɨɫɬ ɯɟɦɨɝɥɨɛɢɧɚ ɡɚ ɠɟɧɟ ʁɟ ɢɡɧɨɫɢɥɚ: 115-165 mg/dl ɢ ɡɚ ɦɭɲɤɚɪɰɟ: 130- 180 mg/dl. ɉɨɞ ɚɧɟɦɢʁɫɤɢɦ ɫɢɧɞɪɨɦɨɦ ɫɟ ɩɨɞɪɚɡɭɦɟɜɚɥɚ ɫɜɚɤɚ ɜɪɟɞɧɨɫɬ ɯɟɦɨɝɥɨɛɢɧɚ ɦɚʃɚ ɨɞ 115 mg/dl ɡɚ ɠɟɧɟ, ɬʁ ɦɚʃɚ ɨɞ 130 mg/dl ɡɚ ɦɭɲɤɚɪɰɟ. ɍɪɟɚ, ɤɪɟɚɬɢɧɢɧ, ɚɥɛɭɦɢɧ, ɤɚɥɢʁɭɦ ɢ ɤɚɥɰɢʁɭɦ ɫɭ ɚɧɚɥɢɡɢɪɚɧɢ ɢɡ ɫɟɪɭɦɚ, ɧɚɤɨɧ ɰɟɧɬɪɢɮɭɝɢɪɚʃɚ ɭɡɨɪɤɚ ɩɭɧɟ ɤɪɜɢ. ɍɪɟɚ Ʉɜɚɧɬɢɬɚɬɢɜɧɨ ɨɞɪɟђɢɜɚʃɟ ɭɪɟɟ ʁɟ ɜɪɲɟɧɨ ɫɩɟɤɬɪɨɮɨɬɨɦɟɬɪɢʁɫɤɨɦ ɍȼ ɦɟɬɨɞɨɦ ɫɚ ɭɪɟɚɡɨɦ ɢ ɝɥɭɬɚɦɚɬ-ɞɟɯɢɞɪɨɝɟɧɚɡɨɦ, ɧɚ ɚɩɚɪɚɬɭ Dimension RxL Max, ɩɪɨɢɡɜɨђɚɱɚ Siemens. Ɋɟɮɟɪɟɧɬɧɟ ɜɪɟɞɧɨɫɬɢ ɫɭ ɢɡɧɨɫɟ 2,5-7,5mmol/L. Ʉɪɟɚɬɢɧɢɧ ȼɪɟɞɧɨɫɬɢ ɤɪɟɚɬɢɧɢɧɚ ɭ ɫɟɪɭɦɭ ɩɚɰɢʁɟɧɚɬɚ ɫɭ ɨɞɪɟђɢɜɚɧɟ ɦɨɞɢɮɢɤɨɜɚɧɨɦ Jaffe ɦɟɬɨɞɨɦ, ɧɚ ɚɩɚɪɚɬɭ Dimension RxL Max, ɩɪɨɢɡɜɨђɚɱɚ Siemens. Ɋɟɮɟɪɟɧɬɧɟ ɜɪɟɞɧɨɫɬɢ ɫɭ ɪɚɡɥɢɱɢɬɟ ɭ ɡɚɜɢɫɧɨɫɬɢ ɨɞ ɩɨɥɚ ɢ ɢɡɧɨɫɟ 44 ɞɨ 88 μmol/L ɤɨɞ ɠɟɧɚ ɢ 53 ɞɨ 106 μmol/L ɤɨɞ ɦɭɲɤɚɪɚɰɚ. Ⱥɥɛɭɦɢɧ Ⱥɧɚɥɢɡɚ ɚɥɛɭɦɢɧɚ ɭ ɫɟɪɭɦɭ ɢɫɩɢɬɢɜɚɧɢɯ ɝɪɭɩɚ ɢɡɜɨђɟɧɚ ʁɟ ɫɩɟɤɬɪɨɮɨɬɨɦɟɬɪɢʁɫɤɢ ɫɚ ɛɪɨɦ-ɤɪɟɡɨɥ ʂɭɛɢɱɚɫɬɢɦ, ɧɚ ɚɩɚɪɚɬɭ Dimension RxL Max, ɩɪɨɢɡɜɨђɚɱɚ Siemens. Ɋɟɮɟɪɟɧɬɧɟ ɜɪɟɞɧɨɫɬɢ ɢɡɧɨɫɟ 32-50 g/L. Ʉɚɥɢʁɭɦ Ⱥɧɚɥɢɡɚ ɤɨɧɰɟɧɬɪɚɰɢʁɟ ɤɚɥɢʁɭɦɚ ɭ ɫɟɪɭɦɭ ɢɫɩɢɬɢɜɚɧɢɯ ɝɪɭɩɚ ɭɪɚђɟɧɚ ʁɟ ɦɟɬɨɞɨɦ ɢɧɞɢɪɟɤɬɧɟ ɩɨɬɟɧɰɢɨɦɟɬɪɢʁɟ, ɧɚ ɚɩɚɪɚɬɭ Dimension RxL Max, ɩɪɨɢɡɜɨђɚɱɚ Siemens. Ɋɟɮɟɪɟɧɬɧɟ ɜɪɟɞɧɨɫɬɢ ɫɭ ɨɞ 3,5 ɞɨ 5,1 mmol/L. Ʉɚɥɰɢʁɭɦ Ɉɞɪɟђɢɜɚʃɟ ɤɨɧɰɟɧɬɪɚɰɢʁɟ ɤɚɥɰɢʁɭɦɚ ɭ ɫɟɪɭɦɭ ɢɫɩɢɬɢɜɚɧɢɯ ɩɚɰɢʁɟɧɚɬɚ ʁɟ ɜɪɲɟɧɨ ɫɩɟɤɬɪɨɮɨɬɨɦɟɬɪɢʁɫɤɢ ɫɚ ɨ-ɤɪɟɡɨɥɮɬɚɥɟɢɧɨɦ, ɧɚ ɚɩɚɪɚɬɭ Dimension RxL Max, ɩɪɨɢɡɜɨђɚɱɚSiemens. Ɋɟɮɟɪɟɧɬɧɟ ɜɪɟɞɧɨɫɬɢ ɫɭ ɨɞ 2,15 ɞɨ 2,55 mmol/L. ɉɨɞ ɯɢɩɟɪɤɚɥɰɟɦɢʁɨɦ ɫɦɨ ɩɨɞɪɚɡɭɦɟɜɚɥɢ ɫɜɚɤɭ ɜɪɟɞɧɨɫɬ ɤɨɪɢɝɨɜɚɧɟ ɤɨɧɰɟɧɬɪɚɰɢʁɟ ɤɚɥɰɢʁɭɦɚ ɤɨʁɚ ʁɟ ɜɢɲɚ ɨɞ ɝɨɪʃɟ ɝɪɚɧɢɰɟ ɪɟɮɟɪɟɧɟɬɧɟ ɜɪɟɞɧɨɫɬɢ. Ʉɨɪɢɝɨɜɚɧɚ ɤɨɧɰɟɧɬɪɚɰɢʁɚ ɤɚɥɰɢʁɭɦɚ ɭ ɫɟɪɭɦɭ ʁɟ ɞɨɛɢʁɟɧɚ ɢɡ ɮɨɪɦɭɥɟ: (40-ɤɨɧɰɟɧɬɪɚɰɢʁɚ ɚɥɛɭɦɢɧɚ)б0,025+ɤɨɧɰɟɧɬɪɚɰɢʁɚ ɤɚɥɰɢʁɭɦɚ ɭ ɫɟɪɭɦɭ. ɆȺɌȿɊɂȳȺɅ ɂ ɆȿɌɈȾȿ 33 3.1.6. Ɇɚɤɪɨɫɤɨɩɫɤɚ ɢ ɦɢɤɪɨɫɤɨɩɫɤɚ ɨɛɪɚɞɚ ɬɤɢɜɚ ɛɭɛɪɟɝɚ ɫɚ ɬɭɦɨɪɨɦ ɍ ɦɚɤɪɨɫɤɨɩɫɤɨʁ ɢ ɦɢɤɪɨɫɤɨɩɫɤɨʁ ɚɧɚɥɢɡɢ ɨɩɟɪɚɬɢɜɧɨɝ ɦɚɬɟɪɢʁɚɥɚ ɢɡ ɩɚɪɰɢʁɚɥɧɢɯ ɢɥɢ ɪɚɞɢɤɚɥɧɢɯ ɧɟɮɪɟɤɬɨɦɢʁɚ ɤɨɪɢɲʄɟɧɟ ɫɭ ɩɪɟɩɨɪɭɤɟ ɫɟɞɦɨɝ ɢɡɞɚʃɚ ɨɧɤɨɥɨɲɤɢɯ ɩɪɨɬɨɤɨɥɚ ɡɚ ɤɚɪɰɢɧɨɦ ɛɭɛɪɟɝɚ ɢɧɬɟɪɧɚɰɢɨɧɚɥɧɢɯ ɭɞɪɭɠɟʃɚ (AJCC/UICC) ɢɡ 2010.ɝɨɞɢɧɟ ɤɨʁɢ ʁɟ ɭ ɩɨɬɩɭɧɨɫɬɢ ɩɪɢɥɚɝɨђɟɧ ɦɟђɭɧɚɪɨɞɧɨʁ TNM ɤɥɚɫɢɮɢɤɚɰɢʁɢ180. ɉɪɟɦɚ ɩɪɨɬɨɤɨɥɭ ɦɚɤɪɨɫɤɨɩɫɤɟ ɢ ɦɢɤɪɨɫɤɨɩɫɤɟ ɚɧɚɥɢɡɟ ɨɞɪɟђɟɧɢ ɫɭ: ɜɪɫɬɚ, ɩɨɞɬɢɩ, ɝɪɚɞɭɫ ɤɚɪɰɢɧɨɦɚ ɛɭɛɪɟɝɚ ɢ ɩɨɫɬɨɩɟɪɚɬɢɜɧɢ ɫɬɚɞɢʁɭɦ. Ɍɤɢɜɧɢ ɭɡɨɪɰɢ ɫɭ ɮɢɤɫɢɪɚɧɢ 5% ɩɭɮɟɪɢɫɚɧɢɦ ɧɟɭɬɪɚɥɧɢɦ ɮɨɪɦɚɥɢɧɨɦ, ɞɟɯɢɞɪɢɫɚɧɢ, ɩɪɨɫɜɟɬʂɟɧɢ ɢ ɩɪɨɠɟɬɢ ɩɚɪɚɮɢɧɨɦ ɭ ɚɩɚɪɚɬɭ ɡɚ ɚɭɬɨɦɚɬɫɤɭ ɮɢɤɫɚɰɢʁɭ ɬɤɢɜɧɢɯ ɭɡɨɪɚɤɚ ASP 300 ɢ ɭɤɚɥɭɩʂɟɧɢ ɭ ɩɚɪɚɮɢɧ. ɍ ɦɚɤɪɨɫɤɨɩɫɤɨʁ ɨɛɪɚɞɢ ɤɨɞ ɦɚɬɟɪɢʁɚɥɚ ɢɡ ɪɚɞɢɤɚɥɧɟ ɧɟɮɪɟɤɬɨɦɢʁɟ, ɨɫɢɦ ɩɨɞɚɬɚɤɚ ɨ ɦɚɫɢ ɛɭɛɪɟɝɚ ɢ ɜɟɥɢɱɢɧɢ ɢ ɥɨɤɚɥɢɡɚɰɢʁɢ ɬɭɦɨɪɚ, ɨɛɚɜɟɡɧɢ ɞɟɨ ɢɡɜɟɲɬɚʁɚ ɩɪɟɞɫɬɚɜʂɚɥɢ ɫɭ ɢ ɩɚɪɚɦɟɬɪɢ ɩɨʁɟɞɢɧɚɱɧɨɝ ɩɪɟɱɧɢɤɚ ɢɥɢ ɡɛɢɪɧɢɯ ɩɪɟɱɧɢɤɚ ɬɭɦɨɪɚ ɢ ʃɟɝɨɜɢɯ ɤɚɪɚɤɬɟɪɢɫɬɢɤɚ ɤɚɨ ɲɬɨ ɫɭ ɛɨʁɚ ɢ ɤɨɧɡɢɫɬɟɧɰɢʁɚ (ɋɥɢɤɚ 1.), ɤɚɨ ɢ ɞɟɝɟɧɟɪɚɬɢɜɧɢɯ ɩɪɨɦɟɧɚ ɩɨɩɭɬ ɰɢɫɬɢɱɧɟ ɞɟɝɟɧɟɪɚɰɢʁɟ ɢɥɢ ɧɟɤɪɨɡɟ (ɋɥɢɤɚ 2.). ɉɨɫɟɛɧɨ ʁɟ ɚɧɚɥɢɡɢɪɚɧ ɨɞɧɨɫ ɞɟɥɨɜɚ ɬɭɦɨɪɚ ɩɪɟɦɚ ɯɢɥɭɫɧɨɦ ɢɥɢ ɩɟɪɢɪɟɧɚɥɧɨɦ ɦɚɫɧɨɦ ɬɤɢɜɭ ɢ ɤɪɜɧɢɦ ɫɭɞɨɜɢɦɚ (ɪɟɧɚɥɧɟ ɚɪɬɟɪɢʁɟ ɢ ɜɟɧɟ ɞɨ ɦɟɫɬɚ ɯɢɪɭɪɲɤɨɝ ɩɪɟɫɟɤɚ)- ɦɢɤɪɨɮɨɬɨɝɪɚɮɢʁɟ 3, 4 ɢ 5. ɋɥɢɤɚ 1. ɋɨɥɢɞɧɚ ɩɨʂɚ ɄȻ ɫɚ ɭɨɛɢɱɚʁɟɧɨɦ ɠɭʄɤɚɫɬɨ-ɫɢɜɨɦɛɨʁɨɦ. ɋɥɢɤɚ 2. ɐɢɫɬɢɱɧɚ ɢ ɯɟɦɨɪɚɝɢʁɫɤɚ ɞɟɝɟɧɟɪɚɰɢʁɚ ɭ ɄȻ ɆȺɌȿɊɂȳȺɅ ɂ ɆȿɌɈȾȿ 34 Ɇɚɬɟɪɢʁɚɥ ɢɡ ɩɚɪɰɢʁɚɥɧɟ ɧɟɮɪɟɤɬɨɦɢʁɟ, ɭɱɢʃɟɧɟ ɤɨɞ 8 ɩɚɰɢʁɟɧɚɬɚ, ɚɧɚɥɢɡɢɪɚɧ ʁɟ ɢ ɩɪɢɦɟɧɨɦ ɢɧɬɪɚɨɩɟɪɚɬɢɜɧɟ ɢɥɢ ex tempore, ɤɚɨ ɢ ɧɚ ɫɬɚɧɞɚɪɞɧɢɦ ɩɪɟɩɚɪɚɬɢɦɚ ɯɟɦɚɬɨɤɫɢɥɢɧ-ɟɨɡɢɧ ɦɟɬɨɞɨɦ ɛɨʁɟʃɚ. ɍ ɦɚɤɪɨɫɤɨɩɫɤɨɦ ɢɡɝɥɟɞɭ ɩɚɪɰɢʁɚɥɧɨ ɪɟɫɟɤɨɜɚɧɨɝ ɞɟɥɚ ɛɭɛɪɟɝɚ ɫɚ ɬɭɦɨɪɨɦ ɨɛɚɜɟɡɧɨ ʁɟ ɨɞɪɟђɟɧɚ ɲɢɪɢɧɚ ɨɱɭɜɚɧɨɝ ɛɭɛɪɟɠɧɨɝ ɩɚɪɟɧɯɢɦɚ (ɫɥɢɤɚ 6.). Ʉɚɨ ɩɨɫɟɛɧɚ ɪɟɫɟɤɰɢɨɧɚ ɢɜɢɰɚ ɢɡ ɨɫɬɚɬɤɚ ɦɚɬɟɪɢʁɚɥɚ ɞɨɫɬɚɜʂɚɧ ʁɟ ʁɨɲ ʁɟɞɚɧ ɭɡɨɪɚɤ. ɋɥɢɤɚ 4. ɂɧɮɢɥɬɪɚɰɢʁɚ ɡɢɞɨɜɚ ɪɟɧɚɥɧɟ ɚɪɬɟɪɢʁɟ ɢ ɜɟɧɟ ɬɭɦɨɪɫɤɢɦ ɬɤɢɜɨɦ, ɛɟɡ ɮɨɪɦɢɪɚʃɚ ɬɪɨɦɛɚ ɭ ɥɭɦɟɧɭ. H&E, ɯ40. ɋɥɢɤɚ3. Ɇɢɧɢɦɚɥɧɚ ɢɜɢɰɚ ɦɢɤɪɨɫɤɨɩɫɤɨɝ ɞɟɥɚ ɩɫɟɭɞɨɢɧɮɢɥɬɪɚɰɢʁɟ ɦɚɫɧɨɝ ɬɤɢɜɚ ɫɜɟɬɥɨʄɟɥɢʁɫɤɢɦ ɄȻ, H&E, ɯ40. ɋɥɢɤɚ 5. Ɍɭɦɨɪɫɤɢ ɬɪɨɦɛ ɭ ɛɭɛɪɟɠɧɨʁ ɜɟɧɢ. H&E, ɯ100 ɆȺɌȿɊɂȳȺɅ ɂ ɆȿɌɈȾȿ 35 ɇɚ ɫɥɢɰɢ 7. ɧɚɥɚɡɢ ɫɟ ɭɡɨɪɚɤ ɬɭɦɨɪɫɤɨɝ ɢ ɨɱɭɜɚɧɨɝ ɞɟɥɚ ɛɭɛɪɟɝɚ ɩɪɢɦɟɧɨɦ ex tempore ɦɟɬɨɞɟ. Ɂɚ ɨɞɪɟђɢɜɚʃɟ ɝɪɚɞɭɫɚ ɄȻ ɩɪɢɦɟʃɟɧ ʁɟ Fuhrman-ɨɜ ɫɢɫɬɟɦ ɫɚ ɭɬɜɪђɢɜɚʃɟɦ 4 ɫɬɟɩɟɧɚ ɞɢɮɟɪɟɧɰɢʁɚɰɢʁɟ. Ɇɢɤɪɨɫɤɨɩɫɤɢ ɫɭ ɩɪɚʄɟɧɢ ɨɫɧɨɜɧɢ ɦɨɪɮɨɥɨɲɤɢ ɤɪɢɬɟɪɢʁɢɦɭ ɧɚ ɤɨʁɢɦɚ ɫɟ ɨɜɚʁ ɝɪɚɞɭɫ ɫɢɫɬɟɦ ɡɚɫɧɢɜɚ ɤɚɨ ɲɬɨ ɫɭ ɜɟɥɢɱɢɧɚ ɢ ɨɛɥɢɤ ɧɭɤɥɟɭɫɚ, ɞɢɫɬɪɢɛɭɰɢʁɢ ɯɪɨɦɚɬɢɧɚ, ɩɨʁɚɜɢ ɧɭɤɥɟɨɥɭɫɚ ɢ ɰɟɥɭɥɚɪɧɨɫɬ ɬɭɦɨɪɫɤɨɝ ɬɤɢɜɚ. Ɉɜɢ ɩɚɪɚɦɟɬɪɢ ɩɪɚʄɟɧɢ ɫɭ ɧɚ ɨɞɝɨɜɚɪɚʁɭʄɢɦ ɭɜɟʄɚʃɢɦɚ ɫɜɟɬɥɨɫɧɨɝ ɦɢɤɪɨɫɤɨɩɚ ɨɞ 100 ɢ 400 ɩɭɬɚ. ɍɨɛɢɱɚʁɟɧɚ ɯɟɬɟɪɨɝɟɧɨɫɬ ɝɪɚɞɭɫɚ ɄȻ ɭ ɪɚɡɧɢɦ ɭɡɨɪɰɢɦɚ ɬɤɢɜɚ ɞɟɮɢɧɢɬɢɜɧɨ ʁɟ ɨɞɪɟђɟɧɚ ɤɪɨɡ ɩɨʂɚ ɫɚ ɧɚʁɜɢɲɢɦ ɝɪɚɞɭɫɨɦ (ɫɥɢɤɚ 8.). Ɇɢɬɨɬɫɤɢ ɢɧɞɟɤɫ ɢ ɩɪɨɰɟɧɚ ɚɧɚɩɥɚɡɢʁɟ ɤɪɨɡ ɞɟɬɟɤɰɢʁɭ ɦɢɬɨɫɤɢɯ ɮɢɝɭɪɚ, ɦɭɥɬɢɧɭɤɥɟɚɪɧɢɯ, ɛɢɡɚɪɧɢɯ ɢɥɢ ɬɭɦɨɪɫɤɢɯ ʄɟɥɢʁɚ ɫɚɪɤɨɦɚɬɨɢɞɧɨɝ ɢɡɝɥɟɞɚ ɨɞɝɨɜɚɪɚɥɚ ɫɭ ɝɪɚɞɭɫɭ 4 (ɫɥɢɤɚ 9.). KȻ ɩɪɟɱɧɢɤɚ 22 mm, ɫɚ ɨɱɭɜɚɧɢɦ ɩɚɪɟɧɯɢɦɨɦ ɛɭɛɪɟɝɚ ɞɨ 20 mm. ɋɥɢɤɚ 6. Ɉɱɭɜɚɧ ɩɚɪɟɧɯɢɦ ɋɜɟɬɥɨʄɟɥɢʁɫɤɢ ɄȻ ɋɥɢɤɚ 7. ȿx temporeɩɪɟɩɚɪɚɬ. Ɇɟɬɨɞɚ ɯɟɦɚɬɨɤɫɢɥɢɧ-ɟɨɡɢɧ, ɯ70. ɆȺɌȿɊɂȳȺɅ ɂ ɆȿɌɈȾȿ 36 3.1.7. ɂɦɭɧɨɯɢɫɬɨɯɟɦɢʁɫɤɨ ɨɞɪɟђɢɜɚʃɟ ɟɤɫɩɪɟɫɢʁɟ TIM-1/KIM-1/HAVCR ɭ ɬɤɢɜɧɢɦ ɩɪɟɫɟɰɢɦɚ Oɛɪɚɞɚ ɬɤɢɜɚ ɢɡ ɭɡɨɪɚɤɚ ɬɭɦɨɪɫɤɨɝ ɢ ɡɞɪɚɜɨɝ ɞɟɥɚ ɬɤɢɜɚ ɛɭɛɪɟɝɚ ɨɛɭɯɜɚɬɢɥɚ ʁɟ ɫɬɚɧɞɚɪɧɭ ɩɪɨɰɟɞɭɪɭ ɮɢɤɫɚɰɢʁɟ ɢ ɫɜɟɬɥɨɫɧɨ-ɦɢɤɪɨɫɤɨɩɫɤɟ ɚɧɚɥɢɡɟ ɩɪɢɦɚɪɧɨ ɧɚ ɯɟɦɚɬɨɤɫɢɥɢɧ-ɟɨɡɢɧ ɛɨʁɟʃɟ.ɉɪɟɦɚ ɩɪɨɬɨɤɨɥɭ ɦɚɤɪɨɫɤɨɩɫɤɟ ɢ ɦɢɤɪɨɫɤɨɩɫɤɟ ɚɧɚɥɢɡɟ ɨɞɪɟђɟɧɚ ʁɟ: ɜɪɫɬɚ, ɩɨɞɬɢɩ, ɝɪɚɞɭɫ ɤɚɪɰɢɧɨɦɚ ɛɭɛɪɟɝɚ ɢ ɩɨɫɬɨɩɟɪɚɬɢɜɧɢ ɫɬɚɞɢʁɭɦ. Ɍɤɢɜɧɢ ɭɡɨɪɰɢ ɫɭ ɮɢɤɫɢɪɚɧɢ 5% ɩɭɮɟɪɢɫɚɧɢɦ ɧɟɭɬɪɚɥɧɢɦ ɮɨɪɦɚɥɢɧɨɦ, ɞɟɯɢɞɪɢɫɚɧɢ, ɩɪɨɫɜɟɬʂɟɧɢ ɢ ɩɪɨɠɟɬɢ ɩɚɪɚɮɢɧɨɦ ɭ ɚɩɚɪɚɬɭ ɡɚ ɚɭɬɨɦɚɬɫɤɭ ɮɢɤɫɚɰɢʁɭ ɬɤɢɜɧɢɯ ɭɡɨɪɚɤɚ ASP 300 ɢ ɭɤɚɥɭɩʂɟɧɢ ɭ ɩɚɪɚɮɢɧ. ɉɚɪɚɮɢɧɫɤɢ ɤɚɥɭɩɢ ɫɭ ɢɫɟɱɟɧɢ ɧɚ ɚɭɬɨɦɚɬɫɤɨɦ ɪɨɬɚɰɢɨɧɨɦ ɦɢɤɪɨɬɨɦɭ Leica RM 2135 ɧɚ ɪɟɡɨɜɟ ɞɟɛʂɢɧɟ 4 . ɉɪɟɫɟɰɢ ɫɭ ɯɜɚɬɚɧɢ ɧɚ Superfrost+ ɩɪɟɞɦɟɬɧɚ ɫɬɚɤɥɚ. Ⱦɟɦɚɫɤɢɪɚʃɟ ɟɩɢɬɨɩɚ ʁɟ ɭɪɚђɟɧɨ ɭ ɪɚɫɬɜɨɪɭ ɡɚ ɞɟɦɚɫɤɢɪɚʃɟ ɟɩɢɬɨɩɚ pH 6.0, DAKO, ɤɚɬ.ɛɪ. S 1700 ɭ ɦɢɤɪɨɬɚɥɚɫɧɨʁ ɩɟʄɧɢɰɢ. Ɂɚ ɢɦɭɧɨɯɢɫɬɨɯɟɦɢʁɫɤɭ ɚɧɚɥɢɡɭ ɤɨɪɢɫɬɢɥɢ ɫɦɨ ɤɚɨ ɩɪɢɦɚɪɧɨ ɚɧɬɢɬɟɥɨ ɦɨɧɨɤɥɨɧɫɤɨ ɦɢɲɢʁɟ ɚɧɬɢ ɯɭɦɚɧɨ ɚɧɬɢɬɟɥɨ TIM- 1/KIM-1/HAVCR(ɤɥɨɧ 219211) , ɮɢɪɦɟ R&D Systems, ɤɚɬ.ɛɪ. MAB 1750, ɭ ɤɨɧɰɟɧɬɪɚɰɢʁɢ ɨɞ 25 µg/ml. Ʉɚɨ ɫɢɫɬɟɦ ɡɚ ɜɢɡɭɟɥɢɡɚɰɢʁɭ ɤɨɪɢɲʄɟɧ ʁɟ EnVision TM+Kit, HRP, Mouse, AEC+, DAKO, ɤɚɬ.ɛɪ. Ʉ 4004. ɐɢɬɨɩɥɚɡɦɚɬɫɤɚɢ/ɢɥɢ ɦɟɦɛɪɚɧɫɤɚ ɪɟɚɤɰɢʁɚ ɩɪɟɞɫɬɚɜʂɚɥɢ ɫɭ ɨɱɟɤɢɜɚɧɢ ɢɦɭɧɨɯɢɫɬɨɯɟɦɢʁɫɤɢ ɪɟɡɭɥɬɚɬ ɡɚ KIM-1. ɍ ɫɬɚɧɞɚɪɞɧɨʁ ɞɢʁɚɝɧɨɫɬɢɰɢ ɢ ɩɪɨɰɟɧɢ ɢɦɭɧɨɯɢɫɬɨɯɟɦɢʁɫɤɢɯ ɪɟɚɤɰɢʁɚ ɭɱɟɫɬɜɨɜɚɥɚ ɫɭ ɞɜɚ ɢɫɤɭɫɧɚ ɩɚɬɨɥɨɝɚ ɭ ɭɪɨɩɚɬɨɥɨɝɢʁɢ. Ɋɟɡɭɥɬɚɬɢ ɫɭ ɨɞɪɟђɟɧɢ ɫɟɦɢɤɜɚɧɬɢɬɚɬɢɜɧɨ ɤɚɨ: ɧɟɝɚɬɢɜɧɚ ɪɟɚɤɰɢʁɚ = ɨɞɫɭɫɬɜɨ ɛɨʁɟʃɚ; 1+ = ɞɨ 10% ɢɦɭɧɨɪɟɚɤɬɢɜɧɢɯ ɬɭɦɨɪɫɤɢɯ ʄɟɥɢʁɚ; 2+ =ɨɞ 11% ɞɨ 50% ɬɭɦɨɪɫɤɢɯ ʄɟɥɢʁɚ ɫɚ ɪɟɚɤɰɢʁɨɦ; 3+ = ɜɢɲɟ ɨɞ 50% ɪɟɚɤɬɢɜɧɢɯ ɬɭɦɨɪɫɤɢɯ ʄɟɥɢʁɚ145,148. ɋɬɟɩɟɧ ɢɧɬɟɧɡɢɬɟɬɚ ɪɟɚɤɰɢʁɚ ɩɪɨɰɟʃɢɜɚɧ ʁɟ ɤɚɨ: ɫɥɚɛ=ɫɜɟɬɥɨɛɪɚɨɧ, ɝɪɚɧɭɥɢɪɚɧɨ ɛɨʁɟʃɟ ɦɟɦɛɪɚɧɨɡɧɨ ɢ/ɢɥɢ ɰɢɬɨɩɥɚɡɦɚɬɫɤɨ ɢ ʁɚɤ= ɬɚɦɧɨɛɪɚɨɧ, ɢɡɪɚɡɢɬɚ ɦɟɦɛɪɚɧɨɡɧɚ ɢ/ɢɥɢ ɰɢɬɨɩɥɚɡɦɚɬɫɤɚ ɪɟɚɤɰɢʁɚ. ɋɥɢɤɚ 8. ɉɨʂɚ ɄȻ ɫɚ ɞɢɮɟɪɟɧɰɢʁɚɰɢʁɨɦ ɨɞ G1 ɞɨ G3, H&E, ɯ40. ɋɥɢɤɚ 9. ɂɧɮɢɥɬɪɚɰɢʁɚ ɡɢɞɨɜɚ ɪɟɧɚɥɧɟ ɚɪɬɟɪɢʁɟ ɢ ɜɟɧɟ ɬɭɦɨɪɫɤɢɦ ɬɤɢɜɨɦ, ɛɟɡ ɮɨɪɦɢɪɚʃɚ ɬɪɨɦɛɚ ɭ ɥɭɦɟɧɭ. H&E, ɯ40. ɆȺɌȿɊɂȳȺɅ ɂ ɆȿɌɈȾȿ 37 ɋɬɚɧɞɚɪɞɧɟ ɛɢɨɯɟɦɢʁɫɤɟ ɚɧɚɥɢɡɟ ɤɪɜɢ ɢ ɭɪɢɧɚ ɭɪɚђɟɧɟ ɫɭ ɭ ɂɧɫɬɢɬɭɬɭ ɡɚ ɛɢɨɯɟɦɢʁɭ ȼɆȺ. Ɉɞɪɟђɢɜɚʃɟ KIM-1ɢ AQP-1 ɭ ɭɪɢɧɭ ɭɪɚђɟɧɨ ʁɟ ɭ Ɉɞɟʂɟʃɭ ɡɚ ɤɥɢɧɢɱɤɭ ɢ ɟɤɫɩɟɪɢɦɟɧɬɚɥɧɭ ɢɦɭɧɨɥɨɝɢʁɭ ɂɧɫɬɢɬɭɬɚ ɡɚ ɦɟɞɢɰɢɧɫɤɚ ɢɫɬɪɚɠɢɜɚʃɚ ȼɆȺ. ɏɢɫɬɨɩɚɬɨɥɨɲɤɚ ɢ ɢɦɭɧɨɯɢɫɬɨɯɟɦɢʁɫɤɚ ɚɧɚɥɢɡɚ ɭɡɨɪɚɤɚ ɬɭɦɨɪɫɤɨɝ ɬɤɢɜɚ ɭɪɚђɟɧɚ ʁɟ ɭ ɂɧɫɬɢɬɭɬɭ ɡɚ ɩɚɬɨɥɨɝɢʁɭ ɢ ɫɭɞɫɤɭ ɦɟɞɢɰɢɧɭ ȼɆȺ. 3.2. ɋɬɚɬɢɫɬɢɱɤɚ ɨɛɪɚɞɚ ɩɨɞɚɬɚɤɚ Ɂɚ ɨɩɢɫ ɩɚɪɚɦɟɬɚɪɚ ɨɞ ɡɧɚɱɚʁɚ, ɚ ɭ ɡɚɜɢɫɧɨɫɬɢ ɨɞ ʃɢɯɨɜɟ ɩɪɢɪɨɞɟ, ɤɨɪɢɲʄɟɧɟ ɫɭ ɦɟɪɟ ɞɟɫɤɪɢɩɬɢɜɧɟ ɫɬɚɬɢɫɬɢɤɟ: ɮɪɟɤɜɟɧɰɢʁɟ, ɩɪɨɰɟɧɬɢ, ɚɪɢɬɦɟɬɢɱɤɚ ɫɪɟɞʃɚ ɜɪɟɞɧɨɫɬ (ɩɪɨɫɟɤ), ɦɟɞɢʁɚɧɚ, ɫɬɚɧɞɚɪɞɧɚ ɞɟɜɢʁɚɰɢʁɚ (ɋȾ) ɢ ɨɩɫɟɝ (ɪɚɫɩɨɧ). Ɂɚ ɧɢɜɨ ɫɬɚɬɢɫɬɢɱɤɟ ɡɧɚɱɚʁɧɨɫɬɢ ɭɫɜɨʁɟɧɚ ʁɟ ɜɪɟɞɧɨɫɬ α=0.05. ɍ ɫɥɭɱɚʁɭ ɜɢɲɟɫɬɪɭɤɨɝ ɬɟɫɬɢɪɚʃɚ ɧɚɞ ɢɫɬɢɦ ɫɟɬɨɦ ɩɨɞɚɬɚɤɚ, ɤɨɪɢɲʄɟɧɚ ʁɟ Bonferroni ɤɨɪɟɤɰɢʁɚ α-ɜɪɟɞɧɨɫɬɢ (α1=0.05/3=0.0167; α2=0.05/6=0.0083).Ɂɚ ɬɟɫɬɢɪɚʃɟ ɡɧɚɱɚʁɧɨɫɬɢ ɪɚɡɥɢɤɚ ɢɡɦɟђɭ ɩɨɧɨɜʂɟɧɢɯ ɦɟɪɟʃɚ (ɢɧɢɰɢʁɚɥɧɨ vs I ɩɨɫɬɨɩɟɪɚɬɢɜɧɚ ɤɨɧɬɪɨɥɚ vs II ɩɨɫɬɨɩɟɪɚɬɢɜɧɚ ɤɨɧɬɪɨɥɚ) ɩɚɪɚɦɟɬɚɪɚ ɨɞ ɡɧɚɱɚʁɚ ɭɧɭɬɚɪ ɝɪɭɩɟ ɨɛɨɥɟɥɢɯ, ɤɨɪɢɲʄɟɧ ʁɟ Fridman-ɨɜ ɬɟɫɬ, Wilcoxon signed rank ɬɟɫɬ i Wilcoxon signed rank ɬɟɫɬ ɫɚ ɤɨɧɬɢɧɭɢɪɚɧɨɦ ɤɨɪɟɤɰɢʁɨɦ. Ɂɚ ɬɟɫɬɢɪɚʃɟ ɪɚɡɥɢɤɚ ɢɡɦɟђɭ ɝɪɭɩɚ (ɨɛɨɥɟɥɢ vs ɡɞɪɚɜɢ), ɚ ɭ ɡɚɜɢɫɧɨɫɬɢ ɨɞ ɩɪɢɪɨɞɟ ɢɫɩɢɬɢɜɚɧɢɯ ɩɚɪɚɦɟɬɚɪɚ, ɤɨɪɢɲʄɟɧɢ ɫɭ: Pearson- ɨɜ2ɬɟɫɬ; Fisher-ɨɜexactɬɟɫɬ; Kruskal Wallis-ɨɜɬɟɫɬ; Wilcoxon rank sum ɬɟɫɬ ɢ Wilcoxon rank sum ɬɟɫɬ ɫɚ ɤɨɧɬɢɧɭɢɪɚɧɨɦ ɤɨɪɟɤɰɢʁɨɦ. Ɂɚ ɢɫɩɢɬɢɜɚʃɟ ɥɢɧɟɚɪɧɟ ɩɨɜɟɡɚɧɨɫɬɢ ɩɚɪɚɦɟɬɚɪɚ ɨɞ ɡɧɚɱɚʁɚ, ɤɨɪɢɲʄɟɧ ʁɟSpearman's rankɤɨɟɮɢɰɢʁɟɧɬ ɤɨɪɟɥɚɰɢʁɟ, ɚ ɡɚ ɦɨɞɟɥ ʃɢɯɨɜɟ ɜɟɡɟ ɤɨɪɢɲʄɟɧɚ ʁɟ ɥɢɧɟɚɪɧɚ ɪɟɝɪɟɫɢʁɚ.Ɂɚ ɢɫɩɢɬɢɜɚʃɟ ɞɢʁɚɝɧɨɫɬɢɱɤɨɝ ɩɨɬɟɧɰɢʁɚɥɚ ɢɧɢɰɢʁɚɥɧɢɯ ɜɪɟɞɧɨɫɬɢ KIM1.0, KIM1.0.ɤɨɪɢɝ, AQP1.0 ɢ AQP1.0.ɤɨɪɢɝ. ɡɚ ɞɢɯɨɬɨɦɧɢ ɢɫɯɨɞ (0-ɡɞɪɚɜɢ; 1-ɨɛɨɥɟɥɢ) ɤɨɪɢɲʄɟɧɚ ʁɟ ɦɟɬɨɞɨɥɨɝɢʁɚ ROC ɤɪɢɜɟ (ɟɧɝɥ. ɫɤɪ. Receiver-Ɉperating- characteristic Curve). Ɂɚ ɨɞɪɟђɢɜɚʃɟ ɩɨɜɪɲɢɧɟ ɢɫɩɨɞ ROC ɤɪɢɜɟ ɢ ɨɞɝɨɜɚɪɚʁɭʄɟ 95% ɢɧɬɟɪɜɚɥɟ ɩɨɜɟɪɟʃɚ (95% CI) ɤɨɪɢɲʄɟɧ ʁɟ DeLong ɦɟɬɨɞ. Ɂɚ ɬɟɫɬɢɪɚʃɟ ɡɧɚɱɚʁɧɨɫɬɢ ɞɢʁɚɝɧɨɫɬɢɱɤɨɝ ɩɨɬɟɧɰɢʁɚɥɚ (AUC ROC) ɩɚɪɚɦɟɬɚɪɚ ɨɞ ɡɧɚɱɚʁɚ (KIM1.0, KIM1.0. ɤɨɪɢɝ, AQP1.0 ɢ AQP1.0. ɤɨɪɢɝ) ɡɚ ɞɢɯɨɬɨɦɧɢ ɢɫɯɨɞ (0-ɡɞɪɚɜɢ; 1-ɨɛɨɥɟɥɢ), ɤɨɪɢɲʄɟɧɚ ʁɟ ɥɨɝɢɫɬɢɱɤɚ ɪɟɝɪɟɫɢɨɧɚ ɚɧɚɥɢɡɚ ɢ Likelihood Ratio ɬɟɫɬ. Ɂɚ ɧɚʁɛɨʂɭ ɝɪɚɧɢɱɧɭ ɜɪɟɞɧɨɫɬ ɩɚɪɚɦɟɬɚɪɚ ɫɚ ɡɧɚɱɚʁɧɢɦ ɞɢʁɚɝɧɨɫɬɢɱɤɢɦ ɩɨɬɟɧɰɢʁɚɥɨɦ ɢɡɚɛɪɚɧɚ ʁɟ ɜɪɟɞɧɨɫɬ ɡɚ ɤɨʁɭ ʁɟ ɩɨɫɬɢɝɧɭɬɚ ɦɚɤɫɢɦɚɥɧɚ ɫɟɧɡɢɬɢɜɧɨɫɬ ɢ ɫɩɟɰɢɮɢɱɧɨɫɬ. Ɂɚ ɢɫɩɢɬɢɜɚʃɟ ɡɧɚɱɚʁɧɨɫɬɢ ɪɚɡɥɢɤɟ ɢɡɦɟђɭ ɞɢʁɚɝɧɨɫɬɢɱɤɢɯ ɩɨɬɟɧɰɢʁɚɥɚ (AUC ROC) ɩɚɪɨɜɚ ɡɚɜɢɫɧɢɯ ɩɚɪɚɦɟɬɚɪɚ (KIM1.0, KIM1.0.ɤɨɪɢɝ; AQP1.0; AQP1.0.ɤɨɪɢɝ) ɡɚ ɞɢɯɨɬɨɦɧɢ ɢɫɯɨɞ (0-ɡɞɪɚɜɢ; 1-ɨɛɨɥɟɥɢ), ɤɨɪɢɲʄɟɧɢ ɫɭ DeLong ɢ Bootstrap ɬɟɫɬ. Ⱥɧɚɥɢɡɚ ɩɨɞɚɬɚɤɚ ʁɟ ɪɚђɟɧɚ ɭ ɫɬɚɬɢɫɬɢɱɤɨɦ ɩɪɨɝɪɚɦɭ R version3.1.1 (2014-07-10) "Sock it to Me" Copyright (C) 2014 The R Foundation for Statistical Computing Platform: i386-w64-mingw32/i386(32-bit) (ɩɪɟɭɡɟɬɨ: 22.10.2014.). Ɂɚ ɝɪɚɮɢɱɤɢ ɩɪɢɤɚɡ ɩɨɞɚɬɚɤɚ ɤɨɪɢɲʄɟɧ ʁɟ Microsoft Office Excel 2007. ɊȿɁɍɅɌȺɌɂ 38 4. ɊȿɁɍɅɌȺɌɂ 4.1. Ɉɩɲɬɟ ɤɚɪɚɤɬɟɪɢɫɬɢɤɟ ɢɫɩɢɬɢɜɚɧɢɯ ɝɪɭɩɚ ɂɫɩɢɬɢɜɚʃɟɦ ɫɭ ɛɢɥɟ ɨɛɭɯɜɚʄɟɧɟ ɞɜɟ ɝɪɭɩɟ ɢɫɩɢɬɚɧɢɤɚ, ɝɪɭɩɚ ɨɛɨɥɟɥɢɯ ɢ ɤɨɧɬɪɨɥɧɚ ɝɪɭɩɚ ɡɞɪɚɜɢɯ ɢɫɩɢɬɚɧɢɤɚ. Ⱦɟɫɤɪɢɩɬɢɜɧɢ ɩɨɞɚɰɢ ɤɥɢɧɢɱɤɢɯ ɤɚɪɚɤɬɟɪɢɫɬɢɤɚ ɢɫɩɢɬɢɜɚɧɢɯ ɝɪɭɩɚ ɩɪɢɤɚɡɚɧɢ ɫɭ ɭ ɬɚɛɟɥɢ ɛɪ. 6. Ɍɚɛɟɥɚɛɪ. 6. Ⱦɟɫɤɪɢɩɬɢɜɧɢ ɩɨɞɚɰɢ ɤɥɢɧɢɱɤɢɯ ɤɚɪɚɤɬɟɪɢɫɬɢɤɚ ɢɫɩɢɬɢɜɚɧɢɯ ɝɪɭɩɚ ɢ ɪɟɡɭɥɬɚɬɢ ɬɟɫɬɢɪɚʃɚ Ʉɚɪɚɤɬɟɪɢɫɬɢɤɟ ɂɫɩɢɬɢɜɚɧɟ ɝɪɭɩɟ Ɍɟɫɬ Ɉɛɨɥɟɥɢ Ɂɞɪɚɜɢ ɉɨɥ Pearson-ɨɜ χ2 ɬɟɫɬ χ22 = 10.1; p= 0.077 ɀɟɧɟ 15 (36.59%) 16 (40%) Ɇɭɲɤɚɪɰɢ 26 (63.41%) 24 (60%) ɋɬɚɪɨɫɬ Wilcoxon rank sum ɬɟɫɬwith continuity correction W= 583 ; p= 0.21829 ɉɪɨɫɟɤ (SD) 56.24 (11.73) 60.33 (16.85) Ɇɟɞɢʁɚɧɚ 54 (35-77) 62 (23-84) Ʉɪɟɚɬɢɧɢɧ (µmol/l) Wilcoxon rank sum ɬɟɫɬwith continuity correction W= 346.5; p= 0.157 ɉɪɨɫɟɤ (ɋȾ) 78.59 (14.84) 75.71 (14.84) Ɇɟɞɢʁɚɧɚ 79 (49-110) 73 (45-100) GFR (ml/min/1,73 m2) Wilcoxon rank sum ɬɟɫɬ with continuity correction W= 482.5; p= 0.903 ɉɪɨɫɟɤ (SD) 87.49 (16.46) 87.35 (17.94) Ɇɟɞɢʁɚɧɚ 89.7 (60-118.2) 86.55 (61-126.8) Ƚɪɭɩɭ ɨɛɨɥɟɥɢɯ ɱɢɧɢɨ ʁɟ 41 ɩɚɰɢʁɟɧɬ, 15 (36,59%) ɨɫɨɛɟ ɠɟɧɫɤɨɝ ɢ 26 (63,41%) ɨɫɨɛɟ ɦɭɲɤɨɝ ɩɨɥɚ, ɫɬɚɪɨɫɬɢ ɨɞ 35 ɞɨ 77 ɝɨɞɢɧɚ (ɦɟɞɢʁɚɧɚ 54). Ʉɨɧɬɪɨɥɧɭ ɝɪɭɩɭ ɱɢɧɢɥɨ ʁɟ 40 ɡɞɪɚɜɢɯ ɢɫɩɢɬɚɧɢɤɚ, 16 (40%) ɨɫɨɛɚ ɠɟɧɫɤɨɝ ɩɨɥɚ ɢ 24 (60%) ɨɫɨɛɚ ɦɭɲɤɨɝ ɩɨɥɚ, ɫɬɚɪɨɫɬɢ ɨɞ 23 ɞɨ 84 ɝɨɞɢɧɟ (ɦɟɞɢʁɚɧɚ 62). Ʉɚɨ ɲɬɨ ɫɟ ɢɡ ɬɚɛɟɥɟ ɛɪ. 6. ɜɢɞɢ ɝɪɭɩɟ ɫɭ ɛɢɥɟ ɯɨɦɨɝɟɧɟ ɩɨ ɩɨɥɭ, ɫɬɚɪɨɫɬɢ ɢ ɛɭɛɪɟɠɧɨʁ ɮɭɧɤɰɢʁɢ ɢɫɤɚɡɚɧɨУ ɩɪɟɤɨ ɤɨɧɰɟɧɬɪɚɰɢʁɟ ɫɟɪɭɦɫɤɨɝ ɤɪɟɚɬɢɧɢɧɚ ɢ ɫɬɨɩɟ ɝɥɨɦɟɪɭɥɫɤɟ ɮɢɥɬɪɚɰɢʁɟ. 4.2. Ʉɚɪɚɤɬɟɪɢɫɬɢɤɟ ɢɫɩɢɬɢɜɚɧɟ ɝɪɭɩɟ ɨɛɨɥɟɥɢɯ ɨɞ ɫɜɟɬɥɨʄɟɥɢʁɫɤɨɝ ɤɚɪɰɢɧɨɦɚ ɛɭɛɪɟɝɚ 4.2.1. Ʉɥɢɧɢɱɤɟ ɤɚɪɚɤɬɟɪɢɫɬɢɤɟ ɝɪɭɩɟ ɨɛɨɥɟɥɢɯ ɍ ɬɚɛɟɥɢ ɛɪ.7. ɩɪɢɤɚɡɚɧɟ ɫɭ ɨɫɧɨɜɧɟ ɤɚɪɚɤɬɟɪɢɫɬɢɤɟ ɝɪɭɩɟ ɨɛɨɥɟɥɢɯ. ɊȿɁɍɅɌȺɌɂ 39 Ɍɚɛɟɥɚ ɛɪ. 7. Ⱦɟɫɤɪɢɩɬɢɜɧɢ ɩɨɞɚɰɢ ɤɥɢɧɢɱɤɢɯ ɤɚɪɚɤɬɟɪɢɫɬɢɤɟ ɝɪɭɩɟ ɨɛɨɥɟɥɢɯ Ʉɚɪɚɤɬɟɪɢɫɬɢɤɟ N (%) ɉɨɥ ɀɟɧɟ 15 (36.59%) Мɭшɤɚɪцɢ 26 (63.41%) ɋɬɚɪɨɫɬ ɉɪɨɫɟɤ (SD) 54.24 (11.73) Мɟɞɢјɚɧɚ (ɨɩɫɟɝ) 54 (35-77) ɋɬɚɪɨɫɬ-ɤɚɬɟɝɨɪɢʁɟ <50 ɝɨɞɢɧɚ 12 (29.27%) >50 ɝɨɞɢɧɚ 29 (70.73%) ɂɧɞɟɤɫ ɬɟɥɟɫɧɟ ɦɚɫɟ (ȻɆɂ) ɉɪɨɫɟɤ 25.59 (5.18) Мɟɞɢјɚɧɚ (ɨɩɫɟɝ) 24 (18.5-46.2) ȻɆɂ-ɤɚɬɟɝɨɪɢʁɟ 18.5-24.9 23 (56.1%) 25-29.9 12 (29.27%) ≥30 6 (14.63%) ɍɤɭɩɧɨ 41 (100%) ɂɫɩɢɬɢɜɚʃɟɦ ʁɟ ɛɢɨ ɨɛɭɯɜɚʄɟɧ 41 ɩɚɰɢʁɟɧɬ, 15 (36,59%) ɨɫɨɛɟ ɠɟɧɫɤɨɝ ɢ 26 (63,41%) ɨɫɨɛɟ ɦɭɲɤɨɝ ɩɨɥɚ. ɉɪɨɫɟɤ ɫɬɚɪɨɫɬɢ ʁɟ ɢɡɧɨɫɢɨ 54,24 (11,73), ɫɚ ɨɩɫɟɝɨɦ ɨɞ 35 ɞɨ 77 ɝɨɞɢɧɚ (ɦɟɞɢʁɚɧɚ 54 ɝɨɞɢɧɟ). ɍ ɫɬɚɪɨɫɧɨʁ ɤɚɬɟɝɨɪɢʁɢ ɦɥɚђɢɯ ɨɞ 50 ɝɨɞɢɧɚ ɛɢɥɨ ʁɟ 12 (29,27%), ɚ ɫɬɚɪɢʁɢɯ ɨɞ 50 ɝɨɞɢɧɚ 29 (70,73%) ɩɚɰɢʁɟɧɚɬɚ. ɍ ɝɪɭɩɢ ɨɛɨɥɟɥɢɯ ɩɪɟ ɨɩɟɪɚɰɢʁɟ 23 (56,1%) ɫɭ ɛɢɥɢ ɧɨɪɦɚɥɧɨ ɭɯɪɚʃɟɧɢ (BMI 18,5-24,9), 12 (29,27%) ɫɭ ɢɦɚɥɢ ɩɪɟɤɨɦɟɪɧɭ ɬɟɥɟɫɧɭ ɬɟɠɢɧɭ (BMI 25-29,9), ɚ 6 (14,63%) ɫɭ ɛɢɥɢ ɝɨʁɚɡɧɢ (BMI≥30). ɇɚʁɧɢɠɚ ɜɪɟɞɧɨɫɬ BMI ɢɡɧɨɫɢɥɚ ʁɟ 18,5, ɧɚʁɜɢɲɚ 46,2 (ɦɟɞɢʁɚɧɚ 24), ɞɨɤ ʁɟ ɩɪɨɫɟɤ BMI ɢɡɧɨɫɢШ 25,59 (5,18). ɍ ɝɪɭɩɢ ɨɛɨɥɟɥɢɯ ɢɫɩɢɬɢɜɚɧɨ ʁɟ ɩɨɫɬɨʁɚʃɟ ɬɪɢ ɩɨɡɧɚɬɚ ɩɨɬɟɧɰɢʁɚɥɧɚ ɮɚɤɬɨɪɚ ɪɢɡɢɤɚ ɡɚ ɪɚɡɜɨʁ ɤɚɪɰɢɧɨɦɚ ɫɜɟɬɥɢɯ ʄɟɥɢʁɚ ɛɭɛɪɟɝɚ ɢ ɬɨ: ɝɨʁɚɡɧɨɫɬ, ɩɭɲɟʃɟ ɢ ɚɪɬɟɪɢʁɫɤɚ ɯɢɩɟɪɬɟɧɡɢʁɚ, ɚ ɞɨɛɢʁɟɧɢ ɞɟɫɪɢɩɬɢɜɧɢ ɩɨɞɚɰɢ ɫɭ ɩɪɢɤɚɡɚɧɢ ɭ ɬɚɛɟɥɢ ɛɪ. 8. Ɍɚɛɟɥɚ ɛɪ. 8. Ⱦɟɫɤɪɢɩɬɢɜɧɢ ɩɨɞɚɰɢ ɢɫɩɢɬɢɜɚɧɢɯ ɮɚɤɬɨɪɚ ɪɢɡɢɤɚ ɡɚ ɪɚɡɜɨʁ ɤɚɪɰɢɧɨɦɚ ɫɜɟɬɥɢɯ ʄɟɥɢʁɚ ɛɭɛɪɟɝɚ ɭ ɝɪɭɩɢ ɨɛɨɥɟɥɢɯ Ɏɚɤɬɨɪɢ ɪɢɡɢɤɚ ɉɪɢɫɭɬɚɧ Ɉɞɫɭɬɚɧ N (%) N (%) Ƚɨʁɚɡɧɨɫɬ 18 (43.9%) 23 (56.1%) ɉɭɲɟʃɟ 25 (60.98%) 16 (39.02%) Ⱥɪɬɟɪɢʁɫɤɚ ɯɢɩɟɪɬɟɧɡɢʁɚ 23 (56,1%) 18 (43,9%) ɊȿɁɍɅɌȺɌɂ 40 Ɉɞ ɭɤɭɩɧɨɝ ɛɪɨʁɚ ɨɛɨɥɟɥɢɯ, 23 (56,1%) ɫɭ ɛɢɥɢ ɧɨɪɦɚɥɧɨ ɭɯɪɚʃɟɧɢ (BMI 18,5-24,9), ɚ 18 (43,9%) ɩɚɰɢʁɟɧɚɬɚ ɫɭ ɛɢɥɢ ɝɨʁɚɡɧɢ. ɍ ɝɪɭɩɢ ɨɛɨɥɟɥɢɯ, 25 (60,98%) ɫɭ ɛɢɥɢ ɩɭɲɚɱɢ, ɚ 16 (39,02%) ɧɢɤɚɞɚ ɧɢɫɭ ɛɢɥɢ ɩɭɲɚɱɢ. Ⱥɪɬɟɪɢʁɫɤɚ ɯɢɩɟɪɬɟɧɡɢʁɚ ʁɟ ɛɢɥɚ ɩɪɢɫɭɬɧɚ ɤɨɞ 23 ɨɛɨɥɟɥɚ (56,1%), ɚ 18 (43,9%) ɫɭ ɢɦɚɥɢ ɧɨɪɦɚɥɚɧ ɤɪɜɧɢ ɩɪɢɬɢɫɚɤ. ɍɝɪɭɩɢ ɨɛɨɥɟɥɢɯ ɢɫɩɢɬɢɜɚɧɨ ʁɟ ɩɨɫɬɨʁɚʃɟ ɫɢɦɩɬɨɦɚ ɢ ɡɧɚɤɨɜɚ ɩɚɪɚɧɟɨɩɥɚɫɬɢɱɤɨɝ ɫɢɧɞɪɨɦɚ, ɚ ɞɨɛɢʁɟɧɢ ɪɟɡɭɥɬɚɬɢ ɫɭ ɩɪɢɤɚɡɚɧɢ ɭ ɬɚɛɟɥɢ ɛɪ. 9. Ɍɚɛɟɥɚ ɛɪ.9. Ⱦɟɫɤɪɢɩɬɢɜɧɢ ɩɨɞɚɰɢ ɢɫɩɢɬɢɜɚɧɢɯ ɩɚɪɚɦɟɬɚɪɚ ɩɚɪɚɧɟɨɩɥɚɫɬɢɱɤɨɝ ɫɢɧɞɪɨɦɚ ɭ ɝɪɭɩɢ ɨɛɨɥɟɥɢɯ ɉɚɪɚɦɟɬɪɢɩɚɪɚɧɟɨɩɥɚɫɬɢɱɤɨɝɫɢɧɞɪɨɦɚ ɉɪɢɫɭɬɚɧ N (%) Ɉɞɫɭɬɚɧ N (%) Ʌɭɦɛɚɥɧɢ ɛɨɥ 7 (17.07%) 34 (82,93%) ɏɟɦɚɬɭɪɢʁɚ 7 (17,07%) 34 (82,93%) Ƚɭɛɢɬɚɤ ɭ ɬɟɥ. ɦɚɫɢ 2 (4,88%) 39 (95,12%) ɉɨɜɢɲɟɧɚ ɬɟɥ. ɬɟɦɩɟɪɚɬɭɪɚ 0 (0%) 41 (100%) Ⱥɧɟɦɢʁɚ 13 (31,70%) 28 (68,30%) ɏɢɩɟɪɤɚɥɰɟɦɢʁɚ 0 (0%) 41 (100%) Ʌɭɦɛɚɥɧɢ ɛɨɥ ɢ ɯɟɦɚɬɭɪɢʁɚ ɫɭ ɛɢɥɢ ɩɪɢɫɭɬɧɢ ɤɨɞ ɢɫɬɨɝ ɛɪɨʁɚ ɨɛɨɥɟɥɢɯ, 7 (17,07%), ɚ 34 (82,93%) ɨɛɨɥɟɥɚ ɧɢɫɭ ɢɦɚɥɢ ɧɢ ɥɭɦɛɚɥɧɢ ɛɨɥ, ɧɢ ɯɟɦɚɬɭɪɢʁɭ. Ƚɭɛɢɬɚɤ ɭ ɬɟɥɟɫɧɨʁ ɦɚɫɢ ʁɟ ɛɢɨ ɩɪɢɫɭɬɚɧ ɫɚɦɨ ɤɨɞ 2 (4,88%) ɨɛɨɥɟɥɚ, ɞɨɤ ʃɢɯ 39 (95,12%) ɧɢʁɟ ɢɦɚɥɨ ɝɭɛɢɬɚɤ ɭ ɬɟɥɟɫɧɨʁ ɦɚɫɢ. ɇɢʁɟɞɚɧ ɨɛɨɥɟɥɢ ɧɢʁɟ ɢɦɚɨ ɩɨɜɢɲɟɧɭ ɬɟɥɟɫɧɭ ɬɟɦɩɟɪɚɬɭɪɭ, ɤɚɨ ɧɢ ɩɨɜɢɲɟɧɭ ɤɨɧɰɟɧɬɪɚɰɢʁɭ ɫɟɪɭɦɫɤɨɝ ɤɚɥɰɢʁɭɦɚ. ɍ ɝɪɭɩɢ ɨɛɨɥɟɥɢɯ ɚɧɟɦɢʁɚ ʁɟ ɛɢɥɚ ɩɪɢɫɭɬɧɚ ɤɨɞ 13 (31,70%) ɨɛɨɥɟɥɢɯ, ɚ 28 (68,30%) ɫɭ ɢɦɚɥɢ ɧɨɪɦɚɥɧɭ ɜɪɟɞɧɨɫɬ ɫɟɪɭɦɫɤɨɝ ɯɟɦɨɝɥɨɛɢɧɚ. 4.2.2. Ȼɢɨɯɭɦɚɪɚɥɧɢ ɩɚɪɚɦɟɬɪɢ ɤɪɜɢ ɢ ɭɪɢɧɚ ɭ ɝɪɭɩɢ ɨɛɨɥɟɥɢɯ-ɩɪɟ ɢ ɩɨɫɥɟ ɨɩɟɪɚɰɢʁɟ 4.2.2.1. Ȼɢɨɯɭɦɨɪɚɥɧɢ ɩɚɪɚɦɟɬɪɢ ɤɪɜɢ ɍ ɬɚɛɟɥɢ ɛɪ. 10. ɧɚɜɟɞɟɧɢ ɫɭ ɛɢɨɯɟɦɢʁɫɤɢ ɩɚɪɚɦɟɬɪɢ ɤɪɜɢ ɤɨʁɢ ɫɭ ɨɞɪɟђɢɜɚɧɢ ɩɪɟ ɨɩɟɪɚɬɢɜɧɨɝ ɥɟɱɟʃɚ ɭ ɝɪɭɩɢ ɨɛɨɥɟɥɢɯ. Ɍɚɛɟɥɚ ɛɪ. 10. Ⱦɟɫɤɪɢɩɬɢɜɧɢ ɩɨɞɚɰɢ ɢɫɩɢɬɢɜɚɧɢɯ ɛɢɨɯɟɦɢʁɫɤɢɯ ɩɚɪɚɦɟɬɚɪɚ ɭ ɝɪɭɩɢ ɨɛɨɥɟɥɢɯ Ȼɢɨɯɭɦɨɪɚɥɧɢ ɩɚɪɚɦɟɬɪɢ ɤɪɜɢ ɉɪɨɫɟɤ (SD) Ɇɟɞɢʁɚɧɚ (ɨɩɫɟɝ) Ȼɪɨʁ ɟɪɢɬɪɨɰɢɬɚ 4.76 (0.47)x1012 4.84 (3.6-5.5)x1012 Ʉɨɧɰ. ɯɟɦɨɝɥɨɛɢɧɚ (mg/dl) 137.1 (15.68) 140 (94.5-163.5) Ʉɨɧɰ.ɤɚɥɰɢʁɭɦɚ (mmol/l) 2.32 (0.12) 2.33 (2.05-2.58) Ʉɨɧɰ. ɤɨɪɢɝɨɜɚɧɨɝ ɤɚɥɰɢʁɭɦɚ (mmol/l) 2.34 (0.1) 2.34 (2.16-2.58) Ʉɨɧɰ. ɤɪɟɚɬɢɧɢɧɚ (µmol/l) 78.59 (14.73) 79 (49-110) Ʉɥɢɪɟɧɫ ɤɪɟɚɬɢɧɢɧɚ (ml/min/1,73 m2) 87.49 (16.46) 89.7 (60-118.2) ɊȿɁɍɅɌȺɌɂ 41 4.2.2.2. ɍɪɢɧɚɪɧɚ ɤɨɧɰɟɧɬɪɚɰɢʁɚ KIM-1 ɍ ɝɪɭɩɢ ɨɛɨɥɟɥɢɯ ɨɞɪɟђɟɧɚ ʁɟ ɚɩɫɨɥɭɬɧɚ ɤɨɧɰɟɧɬɪɚɰɢʁɚ uKIM-1(ng/ml) ɩɪɟ ɨɩɟɪɚɰɢʁɟ, ɧɚ ɩɪɜɨʁ ɢ ɞɪɭɝɨʁ ɩɨɫɬɨɩɟɪɚɬɢɜɧɨʁ ɤɨɧɬɪɨɥɢ, ɚ ʃɢɯɨɜɟ ɜɪɟɞɧɨɫɬɢ ɩɪɢɤɚɡɚɧɟ ɫɭ ɭ ɬɚɛɟɥɢ ɛɪ.11. Ɍɚɛɟɥɚ ɛɪ. 11. Ⱦɟɫɤɪɢɩɬɢɜɧɢ ɩɨɞɚɰɢ ɫɜɢɯ ɚɩɫɨɥɭɬɧɢɯ ɤɨɧɰɟɧɬɪɚɰɢʁɚ uKIM-1(nР/ml) ɩɨ ɦɟɪɟʃɢɦɚ (ɢɧɢɰɢʁɚɥɧɨ, I ɢ II ɩɨɫɬɨɩ. ɤɨɧɬɪɨɥɚ) ɭ ɝɪɭɩɢ ɨɛɨɥɟɥɢɯ Ⱦɟɫɤɪɢɩɬɢɜɧɢ ɩɨɞɚɰɢ ȼɪɟɞɧɨɫɬɢ uKIM-1 (ng/ml) ɂɧɢɰɢʁɚɥɧɟ I ɩɨɫɬɨɩ. ɤɨɧɬɪɨɥɚ II ɩɨɫɬɨɩ. ɤɨɧɬɪɨɥɚ N(%) 40 (97.56%) 36 (90%) 23 (57.5%) ɉɪɨɫɟɤ (ɋȾ) 1.02 (1.49) 0.29 (0.26) 0.14 (0.2) Ɇɟɞɢʁɚɧɚ (ɨɩɫɟɝ) 0.34 (0.038-5) 0.215 (0-0.939) 0.088 (0.039-0.98) ɍ ɬɚɛɟɥɢ ɛɪ. 11. ɫɟ ɜɢɞɢ ɞɚ ʁɟ ɜɪɟɞɧɨɫɬɢ uKIM-1(ng/ml) ɧɚʁɜɢɲɚ ɢɧɢɰɢʁɚɥɧɨ ɬʁ. ɩɪɟ ɨɩɟɪɚɰɢʁɟ. ɉɨɫɬɨɩɟɪɚɬɢɜɧɨ ʃɟɝɨɜɚ ɜɪɟɞɧɨɫɬ ɩɚɞɚ ɢ ɧɚʁɧɢɠɚ ʁɟ ɧɚ ɞɪɭɝɨʁ ɩɨɫɬɨɩɟɪɚɬɢɜɧɨʁ ɤɨɧɬɪɨɥɢ. Ɉɞ ɢɧɬɟɪɟɫɚ ɡɚ ɢɫɬɪɚɠɢɜɚʃɟ ɛɢɥɨ ʁɟ ɢ ɩɨɪɟђɟʃɟ ɩɚɪɨɜɚ ɜɪɟɞɧɨɫɬɢ uKIM-1(ng/ml) ɨɩɫɟɪɜɢɪɚɧɢɯ ɭ ɫɜɚ 3 ɦɟɪɟʃɚ, ɲɬɨ ʁɟ ɛɢɥɨ ɦɨɝɭʄɟ ɭɱɢɧɢɬɢ ɤɨɞ ɩɚɰɢʁɟɧɚɬɚ ɤɨʁɢ ɫɭ ɢɦɚɥɢ ɫɜɟ ɩɨɬɪɟɛɧɟ ɩɨɞɚɬɤɟ. Ⱦɟɫɤɪɢɩɬɢɜɧɢ ɩɨɞɚɰɢ uKIM-1(ng/ml) ɢ ɪɟɡɭɥɬɚɬɢ ɬɟɫɬɢɪɚʃɚ ɩɚɪɨɜɚ ɩɪɢɤɚɡɚɧɢ ɫɭ ɭ ɬɚɛɟɥɢ ɛɪ.12. Tɚɛɟɥɚ ɛɪ. 12. Ⱦɟɫɤɪɢɩɬɢɜɧɢ ɩɨɞɚɰɢ ɢ ɪɟɡɭɥɬɚɬɢ ɬɟɫɬɢɪɚʃɚ uKIM-1 (nР/ml) ɩɨ ɦɟɪɟʃɢɦɚ (ɢɧɢɰɢʁɚɥɧɨ, I ɢ II ɩɨɫɬɨɩ. ɤɨɧɬɪɨɥɚ) ɭ ɝɪɭɩɢ ɨɛɨɥɟɥɢɯ ɉɚɪɨɜɢ ɦɟɪɟʃɚ uKIM-1(ng/ml) Ⱦɟɫɤɪɢɩɬɢɜɧɢ ɩɨɞɚɰɢ Ɍɟɫɬ N ɉɪɨɫɟɤ (ɋȾ) Ɇɟɞɢʁɚɧɚ (ɨɩɫɟɝ) ɢɧɢцɢјɚɥɧɨ vs 36 0.97 (1.52) 0.312 (0.038-5) Wilcoxon signed rank ɬɟɫɬ V= 461; p= 0.044 I ɩɨɫɬɨɩ. ɤɨɧɬɪɨɥɚ 36 0.26 (0.26) 0.215 (0-0.939) ɢɧɢцɢјɚɥɧɨ vs 23 1.09 (1.69) 0.307 (0.038-5) Wilcoxon signed rank ɬɟɫɬ; V= 239; p= 0.0013 II ɩɨɫɬɨɩ. ɤɨɧɬɪɨɥɚ 23 0.14 (0.2) 0.088 (0-0.98) I ɩɨɫɬɨɩ. ɤɨɧɬɪɨɥɚ vs 20 0.23 (0.18) 0.215 (0-0.625) Wilcoxon signed rank ɬɟɫɬ; V= 152; p= 0.0825 II ɩɨɫɬɨɩ. ɤɨɧɬɪɨɥɚ 20 0.16 (0.21) 0.108 (0.042-0.98) ɇɚ ɨɫɧɨɜɭ ɩɨɞɚɬɚɤɚ ɢɡ ɬɚɛɟɥɟ ɛɪ. 12. ɦɨɠɟ ɫɟ ɡɚɤʂɭɱɢɬɢ ɞɚ ɞɨɥɚɡɢ ɞɨ ɡɧɚɱɚʁɧɨɝ ɩɚɞɚ ɜɪɟɞɧɨɫɬɢ uKIM-1(ng/ml) ɨɩɫɟɪɜɢɪɚɧɢɯ ɧɚ I ɢ II ɩɨɫɬɨɩɟɪɚɬɢɜɧɨʁ ɤɨɧɬɪɨɥɢ ɭ ɨɞɧɨɫɭ ɧɚ ɢɧɢɰɢʁɚɥɧɟ ʁɟɪ:  ɤɨɞ 36 ɩɚɰɢʁɟɧɚɬɚ ɤɨʁɢ ɫɭ ɢɦɚɥɢ ɩɨɞɚɬɤɟ uKIM-1(ng/ml) ɨ ɢɧɢɰɢʁɚɥɧɢɦ ɜɪɟɞɧɨɫɬɢɦɚ ɢ ɜɪɟɞɧɨɫɬɢɦɚ ɧɚ I ɩɨɫɬɨɩɟɪɚɬɢɜɧɨʁ ɤɨɧɬɪɨɥɢ, ɜɪɟɞɧɨɫɬɢ ɨɩɫɟɪɜɢɪɚɧɟ ɧɚ I ɩɨɫɬɨɩɟɪɚɬɢɜɧɨʁ ɤɨɧɬɪɨɥɢ ɫɭ ɫɬɚɬɢɫɬɢɱɤɢ ɡɧɚɱɚʁɧɨ ɧɢɠɟ ɭ ɨɞɧɨɫɭ ɧɚ ɢɧɢɰɢʁɚɥɧɟ ɜɪɟɞɧɨɫɬɢ  ɤɨɞ 33 ɩɚɰɢʁɟɧɬɚ ɤɨʁɢ ɫɭ ɢɦɚɥɢ ɩɨɞɚɬɤɟ uKIM-1(ng/ml) ɨ ɢɧɢɰɢʁɚɥɧɢɦ ɜɪɟɞɧɨɫɬɢɦɚ ɢ ɜɪɟɞɧɨɫɬɢɦɚ ɧɚ II ɩɨɫɬɨɩɟɪɚɬɢɜɧɨʁ ɤɨɧɬɪɨɥɢ, ɜɪɟɞɧɨɫɬɢ ɨɩɫɟɪɜɢɪɚɧɟ ɧɚ II ɊȿɁɍɅɌȺɌɂ 42 ɩɨɫɬɨɩɟɪɚɬɢɜɧɨʁ ɤɨɧɬɪɨɥɢ ɫɭ ɫɬɚɬɢɫɬɢɱɤɢ ɡɧɚɱɚʁɧɨ ɧɢɠɟ ɭ ɨɞɧɨɫɭ ɧɚ ɢɧɢɰɢʁɚɥɧɟ ɜɪɟɞɧɨɫɬɢ.  ɤɨɞ 20 ɩɚɰɢʁɟɧɚɬɚ ɤɨʁɢ ɫɭ ɢɦɚɥɢ ɩɨɞɚɬɤɟ ɨ ɜɪɟɞɧɨɫɬɢɦɚ uKIM-1(ng/ml) ɧɚ I ɢ II ɩɨɫɬɨɩɟɪɚɬɢɜɧɨʁ ɤɨɧɬɪɨɥɢ, ɜɪɟɞɧɨɫɬɢ ɨɩɫɟɪɜɢɪɚɧɟ ɧɚ II ɩɨɫɬɨɩɟɪɚɬɢɜɧɨʁ ɤɨɧɬɪɨɥɢ ɫɭ ɧɢɠɟ ɭ ɨɞɧɨɫɭ ɧɚ ɜɪɟɞɧɨɫɬɢ ɨɩɫɟɪɜɢɪɚɧɟ ɧɚ I ɩɨɫɬɨɩɟɪɚɬɢɜɧɨʁ ɤɨɧɬɪɨɥɢ, ɚɥɢ ɛɟɡ ɫɬɚɬɢɫɬɢɱɤɟ ɡɧɚɱɚʁɧɨɫɬɢ. Ɉɞ ɢɧɬɟɪɟɫɚ ɡɚ ɢɫɬɪɚɠɢɜɚʃɟ ɛɢɥɨ ʁɟ ɢ ɩɨɪɟђɟʃɟ ɜɪɟɞɧɨɫɬɢ uKIM-1(ng/ml) ɨɩɫɟɪɜɢɪɚɧɢɯ ɭ ɫɜɚ 3 ɦɟɪɟʃɚ. Ɍɨ ʁɟ ɛɢɥɨ ɦɨɝɭʄɟ ɭɱɢɧɢɬɢ ɤɨɞ 20 ɩɚɰɢʁɟɧɚɬɚ ɤɨʁɢ ɫɭ ɢɦɚɥɢ ɫɜɟ ɩɨɬɪɟɛɧɟ ɩɨɞɚɬɤɟ (Ɍɚɛɟɥɚ ɛɪ. 13.) Tɚɛɟɥɚ ɛɪ. 13. Ⱦɟɫɤɪɢɩɬɢɜɧɢ ɩɨɞɚɰɢ ɢ ɪɟɡɭɥɬɚɬɢ ɬɟɫɬɢɪɚʃɚ ɭ ɝɪɭɩɢ ɨɛɨɥɟɥɢɯ ɤɨʁɢ ɢɦɚʁɭ ɩɨɞɚɬɤɟ uKIM-1 (nР/ml) ɭ ɫɜɢɦ ɦɟɪɟʃɢɦɚ (ɢɧɢɰɢʁɚɥɧɨ, I ɢ II ɩɨɫɬɨɩ. ɤɨɧɬɪɨɥɚ) Ɇɟɪɟʃɚ uKIM-1 Ⱦɟɫɤɪɢɩɬɢɜɧɢ ɩɨɞɚɰɢ Ɍɟɫɬ N ɉɪɨɫɟɤ (ɋȾ) Ɇɟɞɢʁɚɧɚ (ɨɩɫɟɝ) ɢɧɢцɢјɚɥɧɨ 20 1.07 (1.75) 0.29 (0.038-5) Friedman-ɨɜ ɬɟɫɬ χ22 = 9.3; p= 0.009 I ɩɨɫɬɨɩ. ɤɨɧɬɪɨɥɚ 20 0.23 (0.18) 0.215 (0-0.625) II ɩɨɫɬɨɩ. ɤɨɧɬɪɨɥɚ 20 0.16 (0.21) 0.108 (0.042-0.98) ɂɡ ɬɚɛɟɥɟ ɛɪ. 13. ɫɟ ɜɢɞɢ ɞɚ ɩɨɫɬɨʁɢ ɫɬɚɬɢɫɬɢɱɤɢ ɡɧɚɱɚʁɧɚ ɪɚɡɥɢɤɚ ɭ ɜɪɟɞɧɨɫɬɢɦɚ uKIM-1 (ng/ml)ɢɡɦɟђɭ ɦɟɪɟʃɚ. Ⱦɨɞɚɬɧɢɦ ɬɟɫɬɢɪɚʃɟɦ ɞɨɛɢʁɟɧɢ ɫɭ ɪɟɡɭɥɬɚɬɢ ɩɪɢɤɚɡɚɧɢ ɭ ɬɚɛɟɥɢ ɛɪ. 14. Tɚɛɟɥɚ ɛɪ. 14. Ɋɟɡɭɥɬɚɬɢ ɬɟɫɬɢɪɚʃɚ ɢɡɦɟђɭ ɩɚɪɨɜɚ ɦɟɪɟʃɚ ɭ ɝɪɭɩɢ ɨɛɨɥɟɥɢɯ ɤɨʁɢ ɢɦɚʁɭ ɩɨɞɚɬɤɟ uKIM-1 (nР/ml) ɭ ɫɜɢɦ ɦɟɪɟʃɢɦɚ (ɢɧɢɰɢʁɚɥɧɨ, I ɢ II ɩɨɫɬɨɩ. ɤɨɧɬɪɨɥɚ) ɉɚɪɨɜɢ ɦɟɪɟʃɚ uKIM-1 Ɍɟɫɬ ɢɧɢцɢјɚɥɧɨ vs I ɩɨɫɬɨɩ. ɤɨɧɬɪɨɥɚ Wilcoxon signed rank ɬɟɫɬ; V= 461; p*= 0.202 ɢɧɢцɢјɚɥɧɨ vs II ɩɨɫɬɨɩ. ɤɨɧɬɪɨɥɚ Wilcoxon signed rank ɬɟɫɬ; V= 239; p*= 0.006 I ɩɨɫɬɨɩ. ɤɨɧɬɪɨɥɚ vs II ɩɨɫɬɨɩ. ɤɨɧɬɪɨɥɚ Wilcoxon signed rank ɬɟɫɬ; V= 152; p*= 0.082 *BonПОrronТ ɤɨɪɟɤцɢјɚ: 0.05/3=0.0167 Ʉɚɨ ɲɬɨ ɫɟ ɜɢɞɢ ɢɡ ɬɚɛɟɥɟ ɛɪ. 14., ɜɪɟɞɧɨɫɬɢ uKIM-1 (ng/ml) ɨɩɫɟɪɜɢɪɚɧɟ ɧɚ II ɩɨɫɬɨɩɟɪɚɬɢɜɧɨʁ ɤɨɧɬɪɨɥɢ ɫɭ ɫɬɚɬɢɫɬɢɱɤɢ ɡɧɚɱɚʁɧɨ ɧɢɠɟ ɭ ɨɞɧɨɫɭ ɧɚ ɢɧɢɰɢʁɚɥɧɟ ɜɪɟɞɧɨɫɬɢ. ɍ ɢɫɬɪɚɠɢɜɚʃɭ ʁɟ ɭ ɝɪɭɩɢ ɨɛɨɥɟɥɢɯ, ɩɨɪɟɞ ɚɩɫɨɥɭɬɧɟ, ɨɞɪɟђɟɧɚ ɢ ɤɨɧɰɟɧɬɪɚɰɢʁɚ uKIM-1 ɤɨɪɢɝɨɜɚɧɚ ɩɪɟɦɚ ɤɨɧɰɟɧɬɪɚɰɢʁɢ ɤɪɟɚɬɢɧɢɧɚ ɭ ɭɡɨɪɤɭ ɭɪɢɧɚ ɢ ɢɡɪɚɠɟɧɚ ɭ uKIM-1 (ng/mgUcr). ȼɪɟɞɧɨɫɬɢ ɤɨɪɢɝɨɜɚɧɢɯ ɤɨɧɰɟɧɬɪɚɰɢʁɚ uKIM-1 ɫɭ ɨɞɪɟђɟɧɟ ɩɪɟ ɨɩɟɪɚɰɢʁɟ, ɧɚ ɩɪɜɨʁ ɢ ɞɪɭɝɨʁ ɩɨɫɬɨɩɟɪɚɬɢɜɧɨʁ ɤɨɧɬɪɨɥɢ, ɚ ʃɢɯɨɜɟ ɜɪɟɞɧɨɫɬɢ ɩɪɢɤɚɡɚɧɟ ɫɭ ɭ ɬɚɛɟɥɢ ɛɪ. 15. ɊȿɁɍɅɌȺɌɂ 43 Ɍɚɛɟɥɚ ɛɪ. 15. Ⱦɟɫɤɪɢɩɬɢɜɧɢ ɩɨɞɚɰɢ ɫɜɢɯ ɤɨɪɢɝɨɜɚɧɢɯ ɤɨɧɰɟɧɬɪɚɰɢʁɚ uKIM-1(ng/mgUcr) ɩɨ ɦɟɪɟʃɢɦɚ (ɢɧɢɰɢʁɚɥɧɨ, I ɢ II ɩɨɫɬɨɩ. ɤɨɧɬɪɨɥɚ) ɭ ɝɪɭɩɢ ɨɛɨɥɟɥɢɯ Ⱦɟɫɤɪɢɩɬɢɜɧɢ ɩɨɞɚɰɢ ȼɪɟɞɧɨɫɬɢ uKIM-1 ɂɧɢɰɢʁɚɥɧɟ I ɩɨɫɬɨɩ. ɤɨɧɬɪɨɥɚ II ɩɨɫɬɨɩ. ɤɨɧɬɪɨɥɚ N(%) 40 (100%) 36 (90%) 23 (57.5%) ɉɪɨɫɟɤ (ɋȾ) 0.9 (1.84) 0.33 (0.22) 0.17 (0.1) Ɇɟɞɢʁɚɧɚ (ɨɩɫɟɝ) 0.364 (0.076-9.8) 0.278 (0.072-0.814) 0.150 (0.05-0.456) ɂɡ ɬɚɛɟɥɟ ɛɪ. 15. ɫɟ ɜɢɞɢ ɞɚ ʁɟ ɜɪɟɞɧɨɫɬ uKIM-1(ng/mgUcr) ɧɚʁɜɢɲɚ ɢɧɢɰɢʁɚɥɧɨ ɬʁ. ɩɪɟ ɨɩɟɪɚɰɢʁɟ. ɉɨɫɬɨɩɟɪɚɬɢɜɧɨ, ʃɟɝɨɜɚ ɜɪɟɞɧɨɫɬ ɩɚɞɚ ɢ ɧɚʁɧɢɠɚ ʁɟ ɧɚ ɞɪɭɝɨʁ ɩɨɫɬɨɩɟɪɚɬɢɜɧɨʁ ɤɨɧɬɪɨɥɢ. ɉɨɪɟђɟʃɟɦ ɩɚɪɨɜɚ ɤɨɪɢɝɨɜɚɧɢɯ ɜɪɟɞɧɨɫɬɢ uKIM-1(ng/mgUcr) ɨɩɫɟɪɜɢɪɚɧɢɯ ɭ ɫɜɚ 3 ɦɟɪɟʃɚ ɛɢɥɨ ʁɟ ɦɨɝɭʄɟ ɭɱɢɧɢɬɢ ɤɨɞ ɩɚɰɢʁɟɧɚɬɚ ɤɨʁɢ ɫɭ ɢɦɚɥɢ ɫɜɟ ɩɨɬɪɟɛɧɟ ɩɨɞɚɬɤɟ. Ⱦɟɫɤɪɢɩɬɢɜɧɢ ɩɨɞɚɰɢ uKIM-1(ng/mgUcr) ɢ ɪɟɡɭɥɬɚɬɢ ɬɟɫɬɢɪɚʃɚ ɩɚɪɨɜɚ ɩɪɢɤɚɡɚɧɢ ɫɭ ɭ ɬɚɛɟɥɢ ɛɪ. 16. Tɚɛɟɥɚ ɛɪ. 16. Ⱦɟɫɤɪɢɩɬɢɜɧɢ ɩɨɞɚɰɢ ɢ ɪɟɡɭɥɬɚɬɢ ɬɟɫɬɢɪɚʃɚ uKIM-1 (ng/mgUcr) ɩɨ ɦɟɪɟʃɢɦɚ (ɢɧɢɰɢʁɚɥɧɨ, I ɢ II ɩɨɫɬɨɩ. ɤɨɧɬɪɨɥɚ) ɭ ɝɪɭɩɢ ɨɛɨɥɟɥɢɯ ɉɚɪɨɜɢ ɦɟɪɟʃɚ uKIM-1 Ⱦɟɫɤɪɢɩɬɢɜɧɢ ɩɨɞɚɰɢ Ɍɟɫɬ N ɉɪɨɫɟɤ (ɋȾ) Ɇɟɞɢʁɚɧɚ (ɨɩɫɟɝ) ɢɧɢцɢјɚɥɧɨ vs 36 0.92 (1.93) 0.364 (0.076-9.8) Wilcoxon signed rank ɬɟɫɬ V= 417; p= 0.189 I ɩɨɫɬɨɩ. ɤɨɧɬɪɨɥɚ 36 0.33 (0.22) 0.278 (0.072-0.814) ɢɧɢцɢјɚɥɧɨ vs 23 1.18 (2.4) 0.327 (0.076-9.8) Wilcoxon signed rank ɬɟɫɬ; V= 234; p= 0.0001 II ɩɨɫɬɨɩ. ɤɨɧɬɪɨɥɚ 23 0.17 (0.1) 0.150 (0.05-0.456) I ɩɨɫɬɨɩ. ɤɨɧɬɪɨɥɚ vs 20 0.31(0.21) 0.279 (0.072-0.775) Wilcoxon signed rank ɬɟɫɬ; V= 156; p= 0.003 II ɩɨɫɬɨɩ. ɤɨɧɬɪɨɥɚ 20 0.18 (0.1) 0.154 (0.05-0.456) ɇɚ ɨɫɧɨɜɭ ɩɨɞɚɬɚɤɚ ɢɡ ɬɚɛɟɥɟ ɛɪ. 16.ɦɨɠɟ ɫɟ ɡɚɤʂɭɱɢɬɢ ɞɚ ɞɨɥɚɡɢ ɞɨ ɡɧɚɱɚʁɧɨɝ ɩɚɞɚ ɜɪɟɞɧɨɫɬɢ uKIM-1(ng/mgUcr) ɨɩɫɟɪɜɢɪɚɧɢɯ ɧɚ II ɩɨɫɬɨɩɟɪɚɬɢɜɧɨʁ ɤɨɧɬɪɨɥɢ ɭ ɨɞɧɨɫɭ ɧɚ ɢɧɢɰɢʁɚɥɧɟ ɢ ɜɪɟɞɧɨɫɬɢ ɨɩɫɟɪɜɢɪɚɧɟ ɧɚ I ɩɨɫɬɨɩɟɪɚɬɢɜɧɨʁ ɤɨɧɬɪɨɥɢ ʁɟɪ:  ɤɨɞ 36 ɩɚɰɢʁɟɧɚɬɚ ɤɨʁɢ ɫɭ ɢɦɚɥɢ ɩɨɞɚɬɤɟ uKIM-1(ng/mgUcr) ɨ ɢɧɢɰɢʁɚɥɧɢɦ ɜɪɟɞɧɨɫɬɢɦɚ ɢ ɜɪɟɞɧɨɫɬɢɦɚ ɧɚ I ɩɨɫɬɨɩɟɪɚɬɢɜɧɨʁ ɤɨɧɬɪɨɥɢ, ɜɪɟɞɧɨɫɬɢ ɨɩɫɟɪɜɢɪɚɧɟ ɧɚ I ɩɨɫɬɨɩɟɪɚɬɢɜɧɨʁ ɤɨɧɬɪɨɥɢ ɫɭ ɧɢɠɟ ɭ ɨɞɧɨɫɭ ɧɚ ɢɧɢɰɢʁɚɥɧɟ ɜɪɟɞɧɨɫɬɢ, ɚɥɢ ɛɟɡ ɫɬɚɬɢɫɬɢɱɤɟ ɡɧɚɱɚʁɧɨɫɬɢ.  ɤɨɞ 33 ɩɚɰɢʁɟɧɬɚ ɤɨʁɢ ɫɭ ɢɦɚɥɢ ɩɨɞɚɬɤɟ uKIM-1(ng/mgUcr) ɨ ɢɧɢɰɢʁɚɥɧɢɦ ɜɪɟɞɧɨɫɬɢɦɚ ɢ ɜɪɟɞɧɨɫɬɢɦɚ ɧɚ II ɩɨɫɬɨɩɟɪɚɬɢɜɧɨʁ ɤɨɧɬɪɨɥɢ, ɜɪɟɞɧɨɫɬɢ ɨɩɫɟɪɜɢɪɚɧɟ ɧɚ II ɩɨɫɬɨɩɟɪɚɬɢɜɧɨʁ ɤɨɧɬɪɨɥɢ ɫɭ ɫɬɚɬɢɫɬɢɱɤɢ ɡɧɚɱɚʁɧɨ ɧɢɠɟ ɭ ɨɞɧɨɫɭ ɧɚ ɢɧɢɰɢʁɚɥɧɟ ɜɪɟɞɧɨɫɬɢ.  ɤɨɞ 20 ɩɚɰɢʁɟɧɚɬɚ ɤɨʁɢ ɫɭ ɢɦɚɥɢ ɩɨɞɚɬɤɟ ɨ ɜɪɟɞɧɨɫɬɢɦɚ uKIM-1(ng/mgUcr) ɧɚ I ɢ II ɩɨɫɬɨɩɟɪɚɬɢɜɧɨʁ ɤɨɧɬɪɨɥɢ, ɜɪɟɞɧɨɫɬɢ ɨɩɫɟɪɜɢɪɚɧɟ ɧɚ II ɩɨɫɬɨɩɟɪɚɬɢɜɧɨʁ ɤɨɧɬɪɨɥɢ ɊȿɁɍɅɌȺɌɂ 44 ɫɭ ɛɢɥɟ ɫɬɚɬɢɫɬɢɱɤɢ ɡɧɚɱɚʁɧɨ ɧɢɠɟ ɭ ɨɞɧɨɫɭ ɧɚ ɜɪɟɞɧɨɫɬɢ ɨɩɫɟɪɜɢɪɚɧɟ ɧɚ I ɩɨɫɬɨɩɟɪɚɬɢɜɧɨʁ ɤɨɧɬɪɨɥɢ. Ɉɞ ɢɧɬɟɪɟɫɚ ɡɚ ɢɫɬɪɚɠɢɜɚʃɟ ɛɢɥɨ ʁɟ ɢ ɩɨɪɟђɟʃɟ ɜɪɟɞɧɨɫɬɢ ɨɩɫɟɪɜɢɪɚɧɢɯ ɭ ɫɜɚ 3 ɦɟɪɟʃɚ. Ɍɨ ʁɟ ɛɢɥɨ ɦɨɝɭʄɟ ɭɱɢɧɢɬɢ ɤɨɞ 20 ɩɚɰɢʁɟɧɚɬɚ ɤɨʁɢ ɫɭ ɢɦɚɥɢ ɫɜɟ ɩɨɬɪɟɛɧɟ ɩɨɞɚɬɤɟ (Ɍɚɛɟɥɚ ɛɪ. 17.) Tɚɛɟɥɚ ɛɪ. 17. Ⱦɟɫɤɪɢɩɬɢɜɧɢ ɩɨɞɚɰɢ ɢ ɪɟɡɭɥɬɚɬɢ ɬɟɫɬɢɪɚʃɚ ɭ ɝɪɭɩɢ ɨɛɨɥɟɥɢɯ ɤɨʁɢ ɢɦɚʁɭ ɩɨɞɚɬɤɟ uKIM-1 (ng/mgUcr) ɭ ɫɜɢɦ ɦɟɪɟʃɢɦɚ (ɢɧɢɰɢʁɚɥɧɨ, I ɢ II ɩɨɫɬɨɩ. ɤɨɧɬɪɨɥɚ) Ɇɟɪɟʃɚ uKIM-1(ng/mgUcr) Ⱦɟɫɤɪɢɩɬɢɜɧɢ ɩɨɞɚɰɢ Ɍɟɫɬ N ɉɪɨɫɟɤ (ɋȾ) Ɇɟɞɢʁɚɧɚ (ɨɩɫɟɝ) ɢɧɢцɢјɚɥɧɨ 20 1.28 (1.75) 0.337 (0.076-9.8) Friedman-ɨɜ ɬɟɫɬ χ22 = 11.789; p= 0.003 I ɩɨɫɬɨɩ. ɤɨɧɬɪɨɥɚ 20 0.31 (0.21) 0.279 (0.072-0.775) II ɩɨɫɬɨɩ. ɤɨɧɬɪɨɥɚ 20 0.18 (0.1) 0.154 (0.05-0.456) ɂɡ ɬɚɛɟɥɟ ɛɪ. 17. ɫɟ ɜɢɞɢ ɞɚ ɩɨɫɬɨʁɢ ɫɬɚɬɢɫɬɢɱɤɢ ɡɧɚɱɚʁɧɚ ɪɚɡɥɢɤɚ ɭ ɜɪɟɞɧɨɫɬɢɦɚ uKIM-1 (ng/mgUcr) ɢɡɦɟђɭ ɦɟɪɟʃɚ. Ⱦɨɞɚɬɧɢɦ ɬɟɫɬɢɪɚʃɟɦ ɞɨɛɢʁɟɧɢ ɫɭ ɪɟɡɭɥɬɚɬɢ ɩɪɢɤɚɡɚɧɢ ɭ ɬɚɛɟɥɢ ɛɪ. 18. Tɚɛɟɥɚ ɛɪ. 18. Ɋɟɡɭɥɬɚɬɢ ɬɟɫɬɢɪɚʃɚ ɢɡɦɟђɭ ɩɚɪɨɜɚ ɦɟɪɟʃɚ ɭ ɝɪɭɩɢ ɨɛɨɥɟɥɢɯ ɤɨʁɢ ɢɦɚʁɭ ɩɨɞɚɬɤɟ uKIM-1 (ng/mgUcr) ɭ ɫɜɢɦ ɦɟɪɟʃɢɦɚ (ɢɧɢɰɢʁɚɥɧɨ, I ɢ II ɩɨɫɬɨɩ. ɤɨɧɬɪɨɥɚ) ɉɚɪɨɜɢ ɦɟɪɟʃɚ uKIM-1 Ɍɟɫɬ ɢɧɢцɢјɚɥɧɨ vs I ɩɨɫɬɨɩ. ɤɨɧɬɪɨɥɚ Wilcoxon signed rank ɬɟɫɬ; V= 461; p*= 0.169 ɢɧɢцɢјɚɥɧɨ vs II ɩɨɫɬɨɩ. ɤɨɧɬɪɨɥɚ Wilcoxon signed rank ɬɟɫɬ; V= 239; p*= 0.0003 I ɩɨɫɬɨɩ. ɤɨɧɬɪɨɥɚ vs II ɩɨɫɬɨɩ. ɤɨɧɬɪɨɥɚ Wilcoxon signed rank ɬɟɫɬ; V= 152; p*= 0.0035 *BonПОrronТ ɤɨɪɟɤцɢјɚ: 0.05/3=0.0167 Ʉɚɨ ɲɬɨ ɫɟ ɢɡ ɬɚɛɟɥɟ ɛɪ. 18. ɜɢɞɢ, ɜɪɟɞɧɨɫɬɢ uKIM-1(ng/mgUcr) ɨɩɫɟɪɜɢɪɚɧɟ ɧɚ ɞɪɭɝɨʁ ɩɨɫɬɨɩɟɪɚɬɢɜɧɨʁ ɤɨɧɬɪɨɥɢ ɫɭ ɫɬɚɬɢɫɬɢɱɤɢ ɡɧɚɱɚʁɧɨ ɧɢɠɟ ɭ ɨɞɧɨɫɭ ɧɚ ɢɧɢɰɢʁɚɥɧɟ ɜɪɟɞɧɨɫɬɢ. 4.2.2.3. ɍɪɢɧɚɪɧɚ ɤɨɧɰɟɧɬɪɚɰɢʁɚ AQP-1 ɍ ɝɪɭɩɢ ɨɛɨɥɟɥɢɯ ɨɞɪɟђɟɧɚ ʁɟ ɚɩɫɨɥɭɬɧɚ ɤɨɧɰɟɧɬɪɚɰɢʁɚ uAQP-1(ng/ml) ɩɪɟ ɨɩɟɪɚɰɢʁɟ, ɧɚ ɩɪɜɨʁ ɢ ɞɪɭɝɨʁ ɩɨɫɬɨɩɟɪɚɬɢɜɧɨʁ ɤɨɧɬɪɨɥɢ, ɚ ʃɢɯɨɜɟ ɜɪɟɞɧɨɫɬɢ ɩɪɢɤɚɡɚɧɟ ɫɭ ɭ ɬɚɛɟɥɢ ɛɪ. 19. ɊȿɁɍɅɌȺɌɂ 45 Ɍɚɛɟɥɚ ɛɪ. 19. Ⱦɟɫɤɪɢɩɬɢɜɧɢ ɩɨɞɚɰɢ ɫɜɢɯ ɚɩɫɨɥɭɬɧɢɯ ɤɨɧɰɟɧɬɪɚɰɢʁɚ uAQP-1(nР/ml) ɩɨ ɦɟɪɟʃɢɦɚ (ɢɧɢɰɢʁɚɥɧɨ, I ɢ II ɩɨɫɬɨɩ. ɤɨɧɬɪɨɥɚ) ɭ ɝɪɭɩɢ ɨɛɨɥɟɥɢɯ Ⱦɟɫɤɪɢɩɬɢɜɧɢ ɩɨɞɚɰɢ ȼɪɟɞɧɨɫɬɢ uAQP-1(ng/ml) ɂɧɢɰɢʁɚɥɧɟ I ɩɨɫɬɨɩ. ɤɨɧɬɪɨɥɚ II ɩɨɫɬɨɩ. ɤɨɧɬɪɨɥɚ N(%) 39 (95.12%) 37 (90.24%) 23 (57%) ɉɪɨɫɟɤ (ɋȾ) 0.1 (0.04) 0.1 (0.03) 0.2 (0.2) Ɇɟɞɢʁɚɧɚ (ɨɩɫɟɝ) 0.086 (0-0.287) 0.091 (0-0.149) 0.166 (0-0.79) ɍ ɬɚɛɟɥɢ ɛɪ.19. ɫɟ ɜɢɞɢ ɞɚ ɫɭ ɜɪɟɞɧɨɫɬɢ uAQP-1 (ng/ml) ɧɚʁɧɢɠɟ ɢɧɢɰɢʁɚɥɧɨ ɬʁ. ɩɪɟ ɨɩɟɪɚɰɢʁɟ, ɚ ɞɚ ɩɨɫɬɨɩɟɪɚɬɢɜɧɨ ʃɢɯɨɜɚ ɜɪɟɞɧɨɫɬ ɪɚɫɬɟ ɢ ɧɚʁɜɢɲɚ ʁɟ ɧɚ ɞɪɭɝɨʁ ɩɨɫɬɨɩɟɪɚɬɢɜɧɨʁ ɤɨɧɬɪɨɥɢ. Ɉɞ ɢɧɬɟɪɟɫɚ ɡɚ ɢɫɬɪɚɠɢɜɚʃɟ ɛɢɥɨ ʁɟ ɢ ɩɨɪɟђɟʃɟ ɩɚɪɨɜɚ ɜɪɟɞɧɨɫɬɢ uAQP-1(ng/ml) ɨɩɫɟɪɜɢɪɚɧɢɯ ɭ ɫɜɚ 3 ɦɟɪɟʃɚ, ɲɬɨ ʁɟ ɛɢɥɨ ɦɨɝɭʄɟ ɭɱɢɧɢɬɢ ɤɨɞ ɩɚɰɢʁɟɧɚɬɚ ɤɨʁɢ ɫɭ ɢɦɚɥɢ ɫɜɟ ɩɨɬɪɟɛɧɟ ɩɨɞɚɬɤɟ. Ⱦɟɫɤɪɢɩɬɢɜɧɢ ɩɨɞɚɰɢ uAQP-1(ng/ml) ɢ ɪɟɡɭɥɬɚɬɢ ɬɟɫɬɢɪɚʃɚ ɩɚɪɨɜɚ ɩɪɢɤɚɡɚɧɢ ɫɭ ɭ ɬɚɛɟɥɢ ɛɪ. 20. Tɚɛɟɥɚ ɛɪ. 20. Ⱦɟɫɤɪɢɩɬɢɜɧɢ ɩɨɞɚɰɢ ɢ ɪɟɡɭɥɬɚɬɢ ɬɟɫɬɢɪɚʃɚuAQP-1(ng/ml) ɩɨ ɦɟɪɟʃɢɦɚ (ɢɧɢɰɢʁɚɥɧɨ, I ɢ II ɩɨɫɬɨɩ. ɤɨɧɬɪɨɥɚ) ɭ ɝɪɭɩɢ ɨɛɨɥɟɥɢɯ ɉɚɪɨɜɢ ɦɟɪɟʃɚ uAQP-1(ng/ml) Ⱦɟɫɤɪɢɩɬɢɜɧɢ ɩɨɞɚɰɢ Ɍɟɫɬ N ɉɪɨɫɟɤ (ɋȾ) Ɇɟɞɢʁɚɧɚ (ɨɩɫɟɝ) ɢɧɢцɢјɚɥɧɨ vs 36 0.1 (0.05) 0.086 (0-0.287) Wilcoxon signed rank ɬɟɫɬ V= 296; p= 0.566 I ɩɨɫɬɨɩ. ɤɨɧɬɪɨɥɚ 36 0.09 (0.03) 0.09 (0-0.149) ɢɧɢцɢјɚɥɧɨ vs 23 0.1 (0.04) 0.08 (0.073-0.287) Wilcoxon signed rank ɬɟɫɬ; V= 166; p= 0.4028 II ɩɨɫɬɨɩ. ɤɨɧɬɪɨɥɚ 23 0.08 (0.04) 0.083 (0-0.211) I ɩɨɫɬɨɩ. ɤɨɧɬɪɨɥɚ vs 20 0.09 (0.03) 0.093 (0-0.148) Wilcoxon signed rank ɬɟɫɬ; V= 126; p= 0.2196 II ɩɨɫɬɨɩ. ɤɨɧɬɪɨɥɚ 20 0.08 (0.04) 0.085 (0-0.211) ɇɚ ɨɫɧɨɜɭ ɩɨɞɚɬɚɤɚ ɢɡ ɬɚɛɟɥɟ ɛɪ. 20. ɦɨɠɟ ɫɟ ɡɚɤʂɭɱɢɬɢ ɞɚ ɧɟ ɞɨɥɚɡɢ ɞɨ ɫɬɚɬɢɫɬɢɱɤɢ ɡɧɚɱɚʁɧɟ ɩɪɨɦɟɧɟ ɭ ɜɪɟɞɧɨɫɬɢ uAQP-1(ng/ml) ɧɚ ɩɪɜɨʁ ɢ ɞɪɭɝɨʁ ɩɨɫɬɨɩɟɪɚɬɢɜɧɨʁ ɤɨɧɬɪɨɥɢ ɭ ɨɞɧɨɫɭ ɧɚ ɢɧɢɰɢʁɚɥɧɟ, ɤɚɨ ɢ ɢɡɦɟђɭ ɩɪɜɟ ɢ ɞɪɭɝɟ ɩɨɫɬɨɩɟɪɚɬɢɜɧɟ ɤɨɧɬɪɨɥɟ. Ɉɞ ɢɧɬɟɪɟɫɚ ɡɚ ɢɫɬɪɚɠɢɜɚʃɟ ɛɢɥɨ ʁɟ ɢ ɩɨɪɟђɟʃɟ ɜɪɟɞɧɨɫɬɢ uAQP-1(ng/ml) ɨɩɫɟɪɜɢɪɚɧɢɯ ɭ ɫɜɚ 3 ɦɟɪɟʃɚ. Ɍɨ ʁɟ ɛɢɥɨ ɦɨɝɭʄɟ ɭɱɢɧɢɬɢ ɤɨɞ 20 ɩɚɰɢʁɟɧɚɬɚ ɤɨʁɢ ɫɭ ɢɦɚɥɢ ɫɜɟ ɩɨɬɪɟɛɧɟ ɩɨɞɚɬɤɟ (Ɍɚɛɟɥɚ ɛɪ. 21.) ɊȿɁɍɅɌȺɌɂ 46 Tɚɛɟɥɚ ɛɪ. 21. Ⱦɟɫɤɪɢɩɬɢɜɧɢ ɩɨɞɚɰɢ ɢ ɪɟɡɭɥɬɚɬɢ ɬɟɫɬɢɪɚʃɚ ɭ ɝɪɭɩɢ ɨɛɨɥɟɥɢɯ ɤɨʁɢ ɢɦɚʁɭ ɩɨɞɚɬɤɟ uAQP-1 (nР/ml) ɭ ɫɜɢɦ ɦɟɪɟʃɢɦɚ (ɢɧɢɰɢʁɚɥɧɨ, I ɢ II ɩɨɫɬɨɩ. ɤɨɧɬɪɨɥɚ) Ɇɟɪɟʃɚ uAQP-1 (ng/ml) Ⱦɟɫɤɪɢɩɬɢɜɧɢ ɩɨɞɚɰɢ Ɍɟɫɬ N ɉɪɨɫɟɤ (ɋȾ) Ɇɟɞɢʁɚɧɚ (ɨɩɫɟɝ) ɢɧɢцɢјɚɥɧɨ 20 0.1 (0.05) 0.085 (0.073-0.287) Friedman-ɨɜ ɬɟɫɬ χ22 = 0.987; p= 0.6104 I ɩɨɫɬɨɩ. ɤɨɧɬɪɨɥɚ 20 0.09 (0.03) 0.093 (0-0.148) II ɩɨɫɬɨɩ. ɤɨɧɬɪɨɥɚ 20 0.08 (0.04) 0.085 (0-0.211) ɂɡ ɬɚɛɟɥɟ ɛɪ. 21. ɫɟ ɜɢɞɢ ɞɚ ɧɟ ɩɨɫɬɨʁɢ ɫɬɚɬɢɫɬɢɱɤɢ ɡɧɚɱɚʁɧɚ ɪɚɡɥɢɤɚ ɭ ɜɪɟɞɧɨɫɬɢɦɚ uAQP- 1(ng/ml) ɢɡɦɟђɭ ɦɟɪɟʃɚ. ɍ ɢɫɬɪɚɠɢɜɚʃɭ ʁɟ ɭ ɝɪɭɩɢ ɨɛɨɥɟɥɢɯ, ɩɨɪɟɞ ɚɩɫɨɥɭɬɧɟ, ɨɞɪɟђɟɧɚ ɢ ɜɪɟɞɧɨɫɬ ɤɨɪɢɝɨɜɚɧɟ ɤɨɧɰɟɧɬɪɚɰɢʁɟ uAQP-1 (ng/mgUcr). ȼɪɟɞɧɨɫɬɢ ɤɨɪɢɝɨɜɚɧɢɯ ɤɨɧɰɟɧɬɪɚɰɢʁɚ uAQP-1 ɫɭ ɨɞɪɟђɟɧɟ ɩɪɟ ɨɩɟɪɚɰɢʁɟ, ɧɚ ɩɪɜɨʁ ɢ ɞɪɭɝɨʁ ɩɨɫɬɨɩɟɪɚɬɢɜɧɨʁ ɤɨɧɬɪɨɥɢ, ɚ ʃɢɯɨɜɟ ɜɪɟɞɧɨɫɬɢ ɩɪɢɤɚɡɚɧɟ ɫɭ ɭ ɬɚɛɟɥɢ ɛɪ. 22. Ɍɚɛɟɥɚ ɛɪ. 22. Ⱦɟɫɤɪɢɩɬɢɜɧɢ ɩɨɞɚɰɢ ɫɜɢɯ ɤɨɪɢɝɨɜɚɚɧɢɯ ɤɨɧɰɟɧɬɪɚɰɢʁɚ uAQP-1(ng/mgUcr)ɩɨ ɦɟɪɟʃɢɦɚ (ɢɧɢɰɢʁɚɥɧɨ, I ɢ II ɩɨɫɬɨɩ. ɤɨɧɬɪɨɥɚ) ɭ ɝɪɭɩɢ ɨɛɨɥɟɥɢɯ Ⱦɟɫɤɪɢɩɬɢɜɧɢ ɩɨɞɚɰɢ ȼɪɟɞɧɨɫɬɢ uAЉЈ-1(ng/mgUcr) ɂɧɢɰɢʁɚɥɧɟ I ɩɨɫɬɨɩ. ɤɨɧɬɪɨɥɚ II ɩɨɫɬɨɩ. ɤɨɧɬɪɨɥɚ N(%) 39 (95.12%) 37 (90.24%) 23 (57%) ɉɪɨɫɟɤ (ɋȾ) 0.11 (0.09) 0.15 (0.16) 0.2 (0.2) Ɇɟɞɢʁɚɧɚ (ɨɩɫɟɝ) 0.079 (0-0.412) 0.104 (0-0.925) 0.166 (0-0.79) ɍ ɬɚɛɟɥɢ ɛɪ. 22. ɫɟ ɜɢɞɢ ɞɚ ɫɭ ɜɪɟɞɧɨɫɬɢ uAQP-1(ng/mgUcr) ɧɚʁɧɢɠɟ ɢɧɢɰɢʁɚɥɧɨ ɬʁ. ɩɪɟ ɨɩɟɪɚɰɢʁɟ, ɚ ɞɚ ɩɨɫɬɨɩɟɪɚɬɢɜɧɨ ʃɢɯɨɜɚ ɜɪɟɞɧɨɫɬ ɪɚɫɬɟ ɢ ɧɚʁɜɢɲɚ ʁɟ ɧɚ ɞɪɭɝɨʁ ɩɨɫɬɨɩɟɪɚɬɢɜɧɨʁ ɤɨɧɬɪɨɥɢ. Ɉɞ ɢɧɬɟɪɟɫɚ ɡɚ ɢɫɬɪɚɠɢɜɚʃɟ ɛɢɥɨ ʁɟ ɢ ɩɨɪɟђɟʃɟ ɩɚɪɨɜɚ ɜɪɟɞɧɨɫɬɢ uAQP-1 (ng/mgUcr)ɨɩɫɟɪɜɢɪɚɧɢɯ ɭ ɫɜɚ 3 ɦɟɪɟʃɚ, ɲɬɨ ʁɟ ɛɢɥɨ ɦɨɝɭʄɟ ɭɱɢɧɢɬɢ ɤɨɞ ɩɚɰɢʁɟɧɚɬɚ ɤɨʁɢ ɫɭ ɢɦɚɥɢ ɫɜɟ ɩɨɬɪɟɛɧɟ ɩɨɞɚɬɤɟ. Ⱦɟɫɤɪɢɩɬɢɜɧɢ ɩɨɞɚɰɢ uAQP-1(ng/mgUcr) ɢ ɪɟɡɭɥɬɚɬɢ ɬɟɫɬɢɪɚʃɚ ɩɚɪɨɜɚ ɩɪɢɤɚɡɚɧɢ ɫɭ ɭ ɬɚɛɟɥɢ ɛɪ. 23. Tɚɛɟɥɚ ɛɪ. 23. Ⱦɟɫɤɪɢɩɬɢɜɧɢ ɩɨɞɚɰɢ ɢ ɪɟɡɭɥɬɚɬɢ ɬɟɫɬɢɪɚʃɚuAQP-1 (ng/mgUcr) ɩɨ ɦɟɪɟʃɢɦɚ (ɢɧɢɰɢʁɚɥɧɨ, I ɢ II ɩɨɫɬɨɩ. ɤɨɧɬɪɨɥɚ) ɭ ɝɪɭɩɢ ɨɛɨɥɟɥɢɯ ɉɚɪɨɜɢ ɦɟɪɟʃɚ uAQP-1(ng/mgUcr) Ⱦɟɫɤɪɢɩɬɢɜɧɢ ɩɨɞɚɰɢ Ɍɟɫɬ N ɉɪɨɫɟɤ (ɋȾ) Ɇɟɞɢʁɚɧɚ (ɨɩɫɟɝ) ɢɧɢцɢјɚɥɧɨ vs 35 0.12 (0.09) 0.08 (0-0.412) Wilcoxon signed rank ɬɟɫɬ V= 224; p= 0.1382 I ɩɨɫɬɨɩ. ɤɨɧɬɪɨɥɚ 35 0.15 (0.15) 0.105 (0-0.925) ɢɧɢцɢјɚɥɧɨ vs 23 0.13 (0.13) 0.09 (0.023-0.412) Wilcoxon signed rank ɬɟɫɬ; V= 90; p= 0.1511 II ɩɨɫɬɨɩ. ɤɨɧɬɪɨɥɚ 23 0.2 (0.2) 0.166 (0-0.79) I ɩɨɫɬɨɩ. ɤɨɧɬɪɨɥɚ vs 20 0.16 (0.2) 0.094 (0-0.925) Wilcoxon signed rank ɬɟɫɬ; V= 58; p= 0.1418 II ɩɨɫɬɨɩ. ɤɨɧɬɪɨɥɚ 20 0.2 (0.22) 0.124 (0-0.79) ɊȿɁɍɅɌȺɌɂ 47 ɇɚ ɨɫɧɨɜɭ ɩɨɞɚɬɚɤɚ ɢɡ ɬɚɛɟɥɟ ɛɪ. 23. ɫɟ ɦɨɠɟ ɡɚɤʂɭɱɢɬɢ ɞɚ ɞɨɥɚɡɢ ɞɨ ɩɨɪɚɫɬɚ ɜɪɟɞɧɨɫɬɢ uAQP-1(ng/mgUcr) ɧɚ ɩɪɜɨʁ ɢ ɞɪɭɝɨʁ ɩɨɫɬɨɩɟɪɚɬɢɜɧɨʁ ɤɨɧɬɪɨɥɢ ɭ ɨɞɧɨɫɭ ɧɚ ɢɧɢɰɢʁɚɥɧɟ, ɤɚɨ ɢ ɢɡɦɟђɭ ɩɪɜɟ ɢ ɞɪɭɝɟ ɩɨɫɬɨɩɟɪɚɬɢɜɧɟ ɤɨɧɬɪɨɥɟ ɚɥɢ ɪɚɡɥɢɤɟ ɭ ɜɪɟɞɧɨɫɬɢ ɧɢɫɭ ɫɬɚɬɢɫɬɢɱɤɢ ɡɧɚɱɚʁɧɟ. Ɉɞ ɢɧɬɟɪɟɫɚ ɡɚ ɢɫɬɪɚɠɢɜɚʃɟ ɛɢɥɨ ʁɟ ɢ ɩɨɪɟђɟʃɟ ɜɪɟɞɧɨɫɬɢ uAQP-1(ng/mgUcr) ɨɩɫɟɪɜɢɪɚɧɢɯ ɭ ɫɜɚ 3 ɦɟɪɟʃɚ. Ɍɨ ʁɟ ɛɢɥɨ ɦɨɝɭʄɟ ɭɱɢɧɢɬɢ ɤɨɞ 20 ɩɚɰɢʁɟɧɚɬɚ ɤɨʁɢ ɫɭ ɢɦɚɥɢ ɫɜɟ ɩɨɬɪɟɛɧɟ ɩɨɞɚɬɤɟ (Ɍɚɛɟɥɚ ɛɪ. 24.) Tɚɛɟɥɚ ɛɪ. 24. Ⱦɟɫɤɪɢɩɬɢɜɧɢ ɩɨɞɚɰɢ ɢ ɪɟɡɭɥɬɚɬɢ ɬɟɫɬɢɪɚʃɚ ɭ ɝɪɭɩɢ ɨɛɨɥɟɥɢɯ ɤɨʁɢ ɢɦɚʁɭ ɩɨɞɚɬɤɟ uAQP-1(ng/mgUcr) ɭ ɫɜɢɦ ɦɟɪɟʃɢɦɚ (ɢɧɢɰɢʁɚɥɧɨ, I ɢ II ɩɨɫɬɨɩ. ɤɨɧɬɪɨɥɚ) Ɇɟɪɟʃɚ uAQP-1(ng/mgUcr) Ⱦɟɫɤɪɢɩɬɢɜɧɢ ɩɨɞɚɰɢ Ɍɟɫɬ N ɉɪɨɫɟɤ (ɋȾ) Ɇɟɞɢʁɚɧɚ (ɨɩɫɟɝ) ɢɧɢцɢјɚɥɧɨ 20 0.14 (0.1) 0.097 (0.026-0.412) Friedman-ɨɜ ɬɟɫɬ χ22 = 3.26; p= 0.1954 I ɩɨɫɬɨɩ. ɤɨɧɬɪɨɥɚ 20 0.16 (0.2) 0.094 (0-0.925) II ɩɨɫɬɨɩ. ɤɨɧɬɪɨɥɚ 20 0.2 (0.22) 0.124 (0-0.79) ɂɡ ɬɚɛɟɥɟ ɛɪ. 24. ɫɟ ɜɢɞɢ ɞɚ ɧɟ ɩɨɫɬɨʁɢ ɫɬɚɬɢɫɬɢɱɤɢ ɡɧɚɱɚʁɧɚ ɪɚɡɥɢɤɚ ɭ ɜɪɟɞɧɨɫɬɢɦɚ uAQP- 1(ng/mgUcr)ɢɡɦɟђɭ ɦɟɪɟʃɚ. 4.2.3. ɉɚɬɨɯɢɫɬɨɥɨɲɤɟ ɤɚɪɚɤɬɟɪɢɫɬɢɤɟ ɬɭɦɨɪɚ ɭ ɝɪɭɩɢ ɨɛɨɥɟɥɢɯ ɍ ɬɚɛɟɥɢ ɛɪ. 25. ɧɚɜɟɞɟɧɢ ɫɭ ɞɟɫɤɪɢɩɬɢɜɧɢ ɩɨɞɚɰɢ ɩɚɬɨɯɢɫɬɨɥɨɲɤɢɯ ɤɚɪɚɤɬɟɪɢɫɬɢɤɚ ɨɩɟɪɚɬɢɜɧɨ ɨɞɫɬɪɚʃɟɧɢɯ ɤɚɪɰɢɧɨɦɚ ɫɜɟɬɥɢɯ ʄɟɥɢʁɚ ɭ ɝɪɭɩɢ ɨɛɨɥɟɥɢɯ. Ɍɚɛɟɥɚ ɛɪ. 25. Ⱦɟɫɪɢɩɬɢɜɧɢ ɩɨɞɚɰɢ ɩɚɬɨɯɢɫɬɨɥɨɲɤɢɯ ɤɚɪɚɤɬɟɪɢɫɬɢɤɚ ɨɩɟɪɚɬɢɜɧɨ ɨɞɫɬɪɚʃɟɧɢɯ ɤɚɪɰɢɧɨɦɚ ɫɜɟɬɥɢɯ ʄɟɥɢʁɚ ɛɭɛɪɟɝɚ ɭ ɝɪɭɩɢ ɨɛɨɥɟɥɢɯ ɉɚɬɨɯɢɫɬɨɥɨɲɤɟ ɤɚɪɚɤɬɟɪɢɫɬɢɤɟ N (%) ɤɚɪɰɢɧɨɦɚ ɫɜɟɬɥɢɯ ʄɟɥɢʁɚ Ⱦɢɦɟɧɡɢʁɟ ɬɭɦɨɪɚ ɉɪɨɫɟɤ (ɋȾ) 5.44 (2.99) Мɟɞɢјɚɧɚ (ɨɩɫɟɝ) 4.4 (2-13) ɏɢɫɬɨɥɨɲɤɢ ɝɪɚɞɭɫ G1 0 (0%) G2 31 (65,1%) G3 9 (21,95%) G4 1 (2,44%) pT ɫɬɚɞɢʁɭɦ ɊȿɁɍɅɌȺɌɂ 48 1ɚ 13 (31,71%) 1ɛ 10 (24,39%) 2ɚ 3 (7,32%) 3ɚ 15 (36,59%) LV ɫɬɚɞɢʁɭɦ L0V0 7 (17,07%) L1V0 (L0V1) 13 (31,71%) L1V1 21 (51,22%) ɉɨɫɬɨɩɟɪɚɬɢɜɧɢ TNM ɫɬɚɞɢʁɭɦ T1 23 (56,10%) T2 3 (7,32%) T3 13 (31,71%) T4 2(4,88%) KIM-1 ɬɭɦɨɪɫɤɚ ɟɤɫɩɪɟɫɢʁɚ 10-50% (2+) 16 (39,02%) >50% (3+) 23 (56,10%) ɍɤɭɩɧɨ 41 (100%) pT-ɩɚɬɨɥɨшɤɢ ɫɬɚɞɢјɭɦ; LV- ɥɢɦɮɧɨ-ɜɚɫɤɭɥɚɪɧɚ ɢɧɜɚɡɢјɚ Ɉɩɟɪɚɬɢɜɧɨ ʁɟ ɥɟɱɟɧ 41 ɩɚɰɢʁɟɧɬ, ɨɞ ɱɟɝɚ ʁɟ ɤɨɞ 8 (19,51%) ɩɪɢɦɟʃɟɧɚ ɨɬɜɨɪɟɧɚ ɬɪɚɧɫɥɭɦɛɚɥɧɚ ɩɚɪɰɢʁɚɥɧɚ ɧɟɮɪɟɤɬɨɦɢʁɚ, ɚ ɤɨɞ 33 (80,49%) ɨɬɜɨɪɟɧɚ ɬɪɚɧɫɥɭɦɛɚɥɧɚ ɪɚɞɢɤɚɥɧɚ ɧɟɮɪɟɤɬɨɦɢʁɚ ɢ ɤɨɞ ɫɜɢɯ ɨɞɫɬɪɚʃɟɧɢɯ ɬɭɦɨɪɚ ɩɨɫɬɚɜʂɟɧɚ ʁɟ ɩɚɬɨɯɢɫɬɨɥɨɲɤɚ ɞɢʁɚɝɧɨɡɚ ɫɄȻ. ɍ ɭɡɨɪɰɢɦɚ ɬɭɦɨɪɚ ɤɨɞ 2 ɩɚɰɢʁɟɧɬɚ ɩɨɫɬɨʁɚɥɚ ʁɟ ɨɧɤɨɰɢɬɧɚ ʄɟɥɢʁɫɤɚ ɤɨɦɩɨɧɟɧɬɚ ɭ ɨɤɜɢɪɭ ɫɪɟɞʃɟ ɞɢɮɟɪɟɧɬɨɜɚɧɨɝ ɫɄȻ (ɫɥɢɤɚ 10.). ɋɥɢɤɚ 10. Ɂɧɚɱɚʁɧɚ ɡɚɫɬɭɩʂɟɧɨɫɬ ɨɧɤɨɰɢɬɧɟ ɮɨɪɦɟ ɭ ɨɤɜɢɪɭ ɫɄȻ ɫɚ ɛɨɝɚɬɨɦ ɢɧɮɥɚɦɚɬɨɪɧɨɦ ɤɨɦɩɨɧɟɧɬɨɦ, H&E, ɯ40. ɊȿɁɍɅɌȺɌɂ 49 ɉɨɫɬɨɩɟɪɚɬɢɜɧɢ ɩɪɨɫɟɤ ɞɢɦɟɧɡɢʁɚ ɨɞɫɬɪɚʃɟɧɢɯ ɬɭɦɨɪɚ ɢɡɧɨɫɢɨ ʁɟ 5,44 cm (2,99), ɫɚ ɦɟɞɢʁɚɧɨɦ 4,4cm , ɨɩɫɟɝ ɨɞ 2 cm ɞɨ 13 cm. ɇɚʁɜɟʄɢ ɛɪɨʁ ɨɞɫɬɪɚʃɟɧɢɯ ɬɭɦɨɪɚ ɛɢɨ ʁɟ G2 ɯɢɫɬɨɥɨɲɤɨɝ ɝɪɚɞɭɫɚ ɩɨ Furhman-ɭ, 31(65,1%) ɢ G3 ɝɪɚɞɭɫɚ, 9 (21,95%). ɋɚɦɨ ʁɟɞɚɧ ɩɚɰɢʁɟɧɬ (2,44%) ɢɦɚɨ ʁɟ G4 ɝɪɚɞɭɫ ɬɭɦɨɪɚ. ɉɨɫɬɨɩɟɪɚɬɢɜɧɢ ɫɬɚɞɢʁɭɦ I ɞɢʁɚɝɧɨɫɬɢɤɨɜɚɧ ʁɟ ɤɨɞ ɫɜɢɯ ɩɚɰɢʁɟɧɚɬɚ ɫɚ ɭɱɢʃɟɧɨɦ ɩɚɪɰɢʁɚɥɧɨɦ ɧɟɮɪɟɤɬɨɦɢʁɨɦ, ɤɚɨ ɢ Furhman-ɨɜ ɝɪɚɞɭɫ 2. Ɉɞ ɫɟɤɭɧɞɚɪɧɢɯ ɩɪɨɦɟɧɚ ɭ ɬɭɦɨɪɭ, ɰɢɫɬɢɱɧɚ ɞɟɝɟɧɟɪɚɰɢʁɚ ɩɨɫɬɨʁɚɥɚ ʁɟ ɤɨɞ 12 (29,3%) ɯɢɫɬɨɥɨɲɤɢ ɨɛɪɚђɟɧɚ ɭɡɨɪɤɚ. ɇɚʁɜɟʄɢ ɛɪɨʁ ɬɭɦɨɪɚ ʁɟ ɛɢɨ ɩɚɬɨɥɨɲɤɨɝ ɫɬɚɞɢʁɭɦɚ 3ɚ, ɭɤɭɩɧɨ 15 (36,59%) ɢ 1ɚ,13 (31,71%), ɞɨɤ ʁɟ ɧɟɲɬɨ ɦɚʃɢ ɛɪɨʁ, ʃɢɯ 10 (24,39%) ɛɢɥɨ 1ɛ ɩɚɬɨɥɨɲɤɨɝ ɫɬɚɞɢʁɭɦɚ. ɇɚʁɦɚʃɢ ɛɪɨʁ ɬɭɦɨɪɚ, 3 (7,32%) ɛɢɥɨ ʁɟ 2ɚ ɩɚɬɨɥɨɲɤɨɝ ɫɬɚɞɢʁɭɦɚ. ɇɚʁɜɟʄɢ ɛɪɨʁ ɬɭɦɨɪɚ, 21 (51,22%) ɩɨɤɚɡɢɜɚɨ ʁɟ ɡɧɚɤɟ ɥɢɦɮɧɨɜɚɫɤɭɥɚɪɧɟ ɢɧɜɚɡɢʁɟ, 13 (31,71%) ɢɦɚɥɨ ʁɟ ɢɥɢ ɥɢɦɮɧɭ ɢɥɢ ɜɚɫɤɭɥɚɪɧɭ ɢɧɜɚɡɢʁɭ, ɞɨɤ 7 (17,07%) ɬɭɦɨɪɚ ɧɢʁɟ ɩɨɤɚɡɢɜɚɥɨ ɡɧɚɤɟ ɥɢɦɮɧɨɜɚɫɤɭɥɚɪɧɟ ɢɧɜɚɡɢʁɟ. Ɉɞ ɭɤɭɩɧɨɝ ɛɪɨʁɚ ɨɛɨɥɟɥɢɯ, 23 (56,10%) ɛɢɥɨ ʁɟ ɭ TNM I ɩɨɫɬɨɩɟɪɚɬɢɜɧɨɦ ɫɬɚɞɢʁɭɦɭ, 13 (31,71%) ɭ TNM III ɫɬɚɞɢʁɭɦɭ, 3 (7,32%) ɭ TNM II ɢ 2(4,88%) ɭ TNM IV ɩɨɫɬɨɩɟɪɚɬɢɜɧɨɦ ɫɬɚɞɢʁɭɦɭ. Ɍɭɦɨɪɫɤɚ ɟɤɫɩɪɟɫɢʁɚ KIM-1 ɜɟʄɚ ɨɞ 50% (3+) ɛɢɥɚ ʁɟ ɩɪɢɫɭɬɧɚ ɤɨɞ 23 (56,10%) ɬɭɦɨɪɚ, ɚ ɤɨɞ 16 (39,02%) ɛɢɥɚ ʁɟ ɩɪɢɫɭɬɧɚ ɬɭɦɨɪɫɤɚ ɟɤɫɩɪɟɫɢʁɚ 10-50% (2+) ( ɫɥɢɤɟ 11. ɢ 12.). Ʉɨɞ 2 (4,88%) ɩɚɰɢʁɟɧɬɚ ɧɢʁɟ ɩɨɫɬɨʁɚɨ ɩɨɞɚɬɚɤ ɨ ɬɭɦɨɪɫɤɨʁ ɟɤɫɩɪɟɫɢʁɢ KIM-1. ɍ ɭɡɨɪɰɢɦɚ 7 ɨɞ 8 ɩɚɰɢʁɟɧɚɬɚ ɫɚ ɫɄȻ ɢɥɢ 87,5%, ɤɨɞ ɤɨʁɢɯ ʁɟ ɭɱɢʃɟɧɚ ɩɚɪɰɢʁɚɥɧɚ ɧɟɮɪɟɤɬɨɦɢʁɚ, ɧɚђɟɧɚ ʁɟ ɢɡɪɚɡɢɬɨ ɩɨɡɢɬɢɜɧɚ ɪɟɚɤɰɢʁɚ ɡɚ KIM-1. Ʉɨɞ ʁɟɞɧɨɝ ɫɄȻ, ɭ ɦɢɤɪɨɫɤɨɩɫɤɨʁ ɫɥɢɰɢ ɧɚђɟɧɚ ɫɭ ɢ ɩɨʂɚ ɬɭɦɨɪɚ ɫɚ ɫɥɢɤɨɦ ɩɚɩɢɥɚɪɧɨɝ ɩɨɞɬɢɩɚ 1 ɄȻ ɢ ɫɚ ɢɡɪɚɡɢɬɨɦ ɩɨɡɢɬɢɜɧɨɦ ɰɢɬɨɩɥɚɡɦɚɬɫɤɨɦ ɪɟɚɤɰɢʁɨɦ ɡɚ KIM-1 – ɫɥɢɤɟ 13. ɢ 14. ɋɥɢɤɚ 11.Ⱦɢɮɭɡɧɚ ɰɢɬɨɩɥɚɡɦɚɬɫɤɚ ɢɦɭɧɨɪɟɚɤɬɢɧɨɫɬ 3+ ɡɚKIM-1ɭ ɬɭɦɨɪɫɤɢɦ ʄɟɥɢʁɚɦɚ ɫɄȻ. AEC, ɯ100. ɋɥɢɤɚ 12. Ɋɟɚɤɰɢʁɚ 3+ ɭ ɭɡɨɪɤɭ ɫɚ ɫɄȻ ɝɪɚɞɭɫɚ 2 ɢ ɝɪɚɞɭɫɚ 3. AEC, ɯ100. ɊȿɁɍɅɌȺɌɂ 50 Ʉɨɞ 16 (39,02%) ɛɢɥɚ ʁɟ ɩɪɢɫɭɬɧɚ ɬɭɦɨɪɫɤɚ ɟɤɫɩɪɟɫɢʁɚ 10-50% (2+)–ɫɥɢɤɚ 15. ɋɚɦɨ ɭ ʁɟɞɧɨɦ ɨɞ 8 ɫɄȻ ɢɡ ɩɚɪɰɢʁɚɥɧɟ ɧɟɮɪɟɤɬɨɦɢʁɟ ɢɥɢ 12,5%, ɧɚђɟɧɚ ʁɟ ɰɢɫɬɢɱɧɚ ɞɟɝɟɧɟɪɚɰɢʁɚ ɭ ɫɪɟɞʃɟ ɞɢɮɟɪɟɧɬɨɜɚɧɨɦ ɄȻ. ɂɦɭɧɨɯɢɫɬɨɯɟɦɢʁɫɤɢ, ɭɬɜɪђɟɧɚ ʁɟ ɞɢɮɭɡɧɚ ɢ ɢɧɬɟɧɡɢɜɧɚ ɪɟɚɤɰɢʁɚ ɡɚKIM-1 (ɫɥɢɤɟ 16. ɢ 17.). ɋɥɢɤɟ 13. ɢ 14. ɉɚɩɢɥɚɪɧɢ ɩɨɞɬɢɩ ɭ ɨɤɜɢɪɭ ɫɄȻ ɝɪɚɞɭɫɚ 2 (ɥɟɜɨ- ɯɟɦɚɬɨɤɫɢɥɢɧ ɟɨɡɢɧ),ɫɚ ɢɡɪɚɡɢɬɨɦ KIM-1 ɟɤɫɩɪɟɫɢʁɨɦ (ɞɟɫɧɨ). ɋɥɢɤɚ15. ɋɪɟɞʃɟ ɢɡɪɚɠɟɧɚɪɟɚɤɰɢʁɚ ɡɚKIM-1ɭ ɭɡɨɪɤɭ ɫɚ ɫɄȻ ɫɚ ɡɚɯɜɚɬɚʃɟɦ ɥɢɦɮɧɢɯ ɢ ɜɚɫɤɭɥɚɪɧɢɯ ɩɪɨɫɬɨɪɚ. AEC, ɯ40. ɊȿɁɍɅɌȺɌɂ 51 ɐɢɫɬɢɱɧɚ ɞɟɝɟɧɟɪɚɰɢʁɚ ʁɟ ɩɨɫɬɨʁɚɥɚ ɭ ɨɤɨ 33% ɭɡɨɪɚɤɚ ɬɭɦɨɪɚ ɞɨɛɢʁɟɧɢɯ ɪɚɞɢɤɚɥɧɨɦ ɧɟɮɪɟɤɬɨɦɢʁɨɦ. Ɏɨɤɚɥɧɚ, ɫɪɟɞʃɟ ɢɡɪɚɠɟɧɚ ɢ ɩɪɟɬɟɠɧɨ ɦɟɦɛɪɚɧɫɤɚ ɪɟɚɤɰɢʁɚ ɡɚ KIM- 1ɭɨɱɟɧɚ ʁɟ ɭ ɨɜɢɦ ɞɟɥɨɜɢɦɚ ɫɄȻ, ɚɥɢ ɧɢʁɟ ɭɨɱɟɧɚ ɭ ɩɨʂɢɦɚ ɭɨɛɢɱɚʁɟɧɨɝ ɚɥɜɟɨɥɚɪɧɨɝ ɢɡɝɥɟɞɚ (ɫɥɢɤɚ 18.). ɍ ɟɩɢɬɟɥɭ ɫɚɛɢɪɧɢɯ ɤɚɧɚɥɢʄɚ ɨɞɫɬɪɚʃɟɧɢɯ ɛɭɛɪɟɝɚ, ɢɡ ɧɟɬɭɦɨɪɫɤɨɝ ɬɤɢɜɚ, ɩɪɢɦɟɪ ɫɪɟɞʃɟ ɢɡɪɚɠɟɧɟ ɢɦɭɧɨɪɟɚɤɬɢɜɧɨɫɬɢ-ɫɥɢɤɚ 19. ɋɥɢɤɚ 16. ɋɪɟɞʃɟ ɞɢɮɟɪɟɧɬɨɜɚɧɢ ɫɄȻ ɫɚ ɰɢɫɬɢɱɧɨɦ ɞɟɝɟɧɟɪɚɰɢʁɨɦ, H&E, ɯ100. ɋɥɢɤɚ17. KIM-1 3+ ɭ ɢɫɬɨɦ ɭɡɨɪɤɭ, AEC, ɯ40. ɋɥɢɤɚ18. ɋɪɟɞʃɟ ɢɡɪɚɠɟɧɚ KIM-1ɟɤɫɩɪɟɫɢʁɚ ɭ ɰɟɧɬɪɚɥɧɨɦ ɞɟɥɭ ɄȻ. AEC, ɯ100. ɊȿɁɍɅɌȺɌɂ 52 ɍ ɭɡɨɪɰɢɦɚ ɬɤɢɜɚ ɄȻ ɝɪɚɞɭɫɚ 3, ɭɨɱɟɧɚ ʁɟ ɰɢɬɨɩɥɚɡɦɚɬɫɤɚ ɢɦɭɧɨɪɟɚɤɬɢɜɧɨɫɬ ɨɡɧɚɱɟɧɚ ɤɚɨ 2+. Ʉɨɞ ɫɚɪɤɨɦɚɬɨɢɞɧɟ ɮɨɪɦɟ ɄȻ, ɫɚɦɨ ɭ ɞɟɥɨɜɢɦɚ ɬɭɦɨɪɚ ɫɚ ɪɚɞɛɨɢɞɧɢɦ ɢɡɝɥɟɞɨɦ, ɭɨɱɟɧɚ ʁɟ ɦɟɦɛɪɚɧɫɤɚ ɢɦɭɧɨɪɟɚɤɬɢɜɧɨɫɬ ɫɪɟɞʃɟɝ ɢɧɬɟɧɡɢɬɟɬɚ (ɫɥɢɤɟ 20. ɢ 21.). ɋɥɢɤɚ 19.Ʉɨɧɬɪɨɥɧɚ, ɩɨɡɢɬɢɜɧɚ ɪɟɚɤɰɢʁɚ ɡɚKIM-1 ɭ ɧɟɬɭɦɨɪɫɤɨɦ ɞɟɥɭ ɛɭɛɪɟɝɚ. AEC, ɯ40. ɋɥɢɤɚ20. Ɏɨɤɚɥɧɚ ɪɟɚɤɬɢɜɧɨɫɬ, 2+,KIM-1.AEC, ɯ200. ɋɥɢɤɚ 21. Ɇɟɦɛɪɚɧɫɤɚ ɢ ɮɨɤɚɥɧɚ ɪɟɚɤɬɢɜɧɨɫɬ, 2+,KIM-1. AEC, ɯ200. ɊȿɁɍɅɌȺɌɂ 53 4.3. Ʉɨɦɩɚɪɚɰɢʁɚ ɤɨɧɰɟɧɬɪɚɰɢʁɚ KIM-1 ɢ AQP-1 ɢɡɦɟђɭ ɢɫɩɢɬɢɜɚɧɢɯ ɝɪɭɩɚ 4.3.1. Ʉɨɦɩɚɪɚɰɢʁɚ ɭɪɢɧɚɪɧɟ ɤɨɧɰɟɧɬɪɚɰɢʁɟ KIM-1 ɢɡɦɟђɭ ɢɫɩɢɬɢɜɚɧɢɯ ɝɪɭɩɚ ɍ ɢɫɬɪɚɠɢɜɚʃɭ ʁɟ ɫɩɪɨɜɟɞɟɧɨ ɩɨɪɟђɟʃɟ ɜɪɟɞɧɨɫɬɢ ɚɩɫɨɥɭɬɧɟ ɤɨɧɰɟɧɬɪɚɰɢʁɟ uKIM-1 (ng/ml) ɭ ɝɪɭɩɢ ɡɞɪɚɜɢɯ ɢ uKIM-1 (ng/ml) ɩɨ ɦɟɪɟʃɢɦɚ (ɢɧɢɰɢʁɚɥɧɨ ɢɥɢ ɩɪɟɨɩɟɪɚɬɢɜɧɨ, ɩɪɜɚ ɢ ɞɪɭɝɚ ɩɨɫɬɨɩɟɪɚɬɢɜɧɚ ɤɨɧɬɪɨɥɚ) ɭ ɝɪɭɩɢ ɨɛɨɥɟɥɢɯ. Ⱦɟɫɤɪɢɩɬɢɜɧɢ ɩɨɞɚɰɢ ɢ ɪɟɡɭɥɬɚɬɢ ɬɟɫɬɢɪɚʃɚ ɩɪɢɤɚɡɚɧɢ ɫɭ ɭ ɬɚɛɟɥɢ ɛɪ. 26. Ɍɚɛɟɥɚ ɛɪ. 26. Ⱦɟɫɤɪɢɩɬɢɜɧɢ ɩɨɞɚɰɢ ɢ ɪɟɡɭɥɬɚɬɢ ɬɟɫɬɢɪɚʃɚ uKIM-1 (nР/ml) ɭ ɝɪɭɩɢ ɡɞɪɚɜɢɯ ɢ uKIM-1 (nР/ml) ɩɨ ɦɟɪɟʃɢɦɚ (ɢɧɢɰɢʁɚɥɧɨ, I ɢ II ɩɨɫɬɨɩ. ɤɨɧɬɪɨɥɚ) ɭ ɝɪɭɩɢ ɨɛɨɥɟɥɢɯ ɉɚɪɨɜɢ ɦɟɪɟʃɚ uKIM-1(ng/ml) Ⱦɟɫɤɪɢɩɬɢɜɧɢ ɩɨɞɚɰɢ Wilcoxon signed rank ɬɟɫɬ with continuity correction N ɉɪɨɫɟɤ (ɋȾ) Ɇɟɞɢʁɚɧɚ (ɨɩɫɟɝ) Ɂɞɪɚɜɢ vs 40 0.14 (0.08) 0.122 (0.036-0.281) V= 150.5 p= 5.034*10-6 Ȼɨɥɟɫɧɢ (ɢɧɢцɢјɚɥɧɚ ɜ.) 40 1.02 (1.49) 0.34 (0.038-5) Ɂɞɪɚɜɢ vs 40 0.14 (0.08) 0.122 (0.036-0.281) V= 298.5 p= 0.045 Ȼɨɥɟɫɧɢ (I ɩɨɫɬ. ɤɨɧ.) 36 0.29 (0.26) 0.215 (0-0.939) Ɂɞɪɚɜɢ vs 40 0.14 (0.08) 0.122 (0.036-0.281) V= 340 p= 0.176 Ȼɨɥɟɫɧɢ (II ɩɨɫɬ. ɤɨɧ.) 23 0.14 (0.2) 0.088 (0.039-0.98) ɂɡ ɬɚɛɟɥɟ ɛɪ. 26. ɫɟ ɜɢɞɢ ɞɚ ʁɟ ɢɧɢɰɢʁɚɥɧɚ ɜɪɟɞɧɨɫɬ ɚɩɫɨɥɭɬɧɟ ɤɨɧɰɟɧɬɪɚɰɢʁɟ uKIM-1 (ng/ml) ɭ ɝɪɭɩɢ ɨɛɨɥɟɥɢɯ ɫɬɚɬɢɫɬɢɱɤɢ ɡɧɚɱɚʁɧɨ ɜɢɲɚ ɭ ɨɞɧɨɫɭ ɧɚ ʃɟɧɭ ɜɪɟɞɧɨɫɬ ɭ ɝɪɭɩɢɡɞɪɚɜɢɯ (p=5.034*10-6). ɇɚ ɩɪɜɨʁ ɩɨɫɬɨɩɟɪɚɬɢɜɧɨʁ ɤɨɧɬɪɨɥɢ ɜɪɟɞɧɨɫɬ uKIM-1 (ng/ml) ɭ ɝɪɭɩɢ ɨɛɨɥɟɥɢɯ ɩɚɞɚ ɢ ɞɨɫɬɢɠɟ ɧɚʁɧɢɠɭ ɜɪɟɞɧɨɫɬ ɧɚ ɞɪɭɝɨʁ ɩɨɫɬɨɩɟɪɚɬɢɜɧɨʁ ɤɨɧɬɪɨɥɢ. ɇɚ ɩɪɜɨʁ ɩɨɫɬɨɩɟɪɚɬɢɜɧɨʁ ɤɨɧɬɪɨɥɢ ɩɨɫɬɨʁɢ ɫɬɚɬɢɫɬɢɱɤɢ ɡɧɚɱɚʁɧɚ ɪɚɡɥɢɤɚ ɢɡɦɟђɭ ɝɪɭɩɚ (p= 0.045). ɇɚ ɞɪɭɝɨʁ ɩɨɫɬɨɩɟɪɚɬɢɜɧɨʁ ɤɨɧɬɪɨɥɢ ɧɟ ɩɨɫɬɨʁɢ ɫɬɚɬɢɫɬɢɱɤɢ ɡɧɚɱɚʁɧɚ ɪɚɡɥɢɤɚ ɢɡɦɟђɭ ɝɪɭɩɚ (p=0.176). ɇɚ ɝɪɚɮɢɤɨɧɭ ɛɪ. 1. ɩɪɢɤɚɡɚɧɟ ɫɭ ɜɪɟɞɧɨɫɬɢ ɚɩɫɨɥɭɬɧɟ ɤɨɧɰɟɧɬɪɚɰɢʁɟ uKIM-1 (ng/ml) ɭ ɝɪɭɩɢ ɡɞɪɚɜɢɯ ɢ uKIM-1 (ng/ml) ɩɨ ɦɟɪɟʃɢɦɚ (ɢɧɢɰɢʁɚɥɧɨ ɢɥɢ ɩɪɟɨɩɟɪɚɬɢɜɧɨ, ɩɪɜɚ ɢ ɞɪɭɝɚ ɩɨɫɬɨɩɟɪɚɬɢɜɧɚ ɤɨɧɬɪɨɥɚ) ɭ ɝɪɭɩɢ ɨɛɨɥɟɥɢɯ. ɊȿɁɍɅɌȺɌɂ 54 Ƚɪɚɮɢɤɨɧ ɛɪ.1. ɉɪɢɤɚɡ uKIM-1 (nР/ml) ɭ ɝɪɭɩɢ ɡɞɪɚɜɢɯ ɢ uKIM-1 (nР/ml) ɩɨ ɦɟɪɟʃɢɦɚ (ɢɧɢɰɢʁɚɥɧɨ, I ɢ II ɩɨɫɬɨɩ. ɤɨɧɬɪɨɥɚ) ɭ ɝɪɭɩɢ ɨɛɨɥɟɥɢɯ Ⱦɟɫɤɪɢɩɬɢɜɧɢ ɩɨɞɚɰɢ ɢ ɪɟɡɭɥɬɚɬɢ ɬɟɫɬɢɪɚʃɚ ɢɡɦɟђɭ ɝɪɭɩɟ ɡɞɪɚɜɢɯ ɢ ɝɪɭɩɟ ɨɛɨɥɟɥɢɯ ɫɩɪɨɜɟɞɟɧɢ ɫɭ ɢ ɡɚ ɤɨɪɢɝɨɜɚɧɭ ɜɪɟɞɧɨɫɬ uKIM-1(ng/mgUcr)ɢ ɩɪɢɤɚɡɚɧɢ ɫɭ ɭ ɬɚɛɟɥɢ ɛɪ. 27. Ɍɚɛɟɥɚ ɛɪ. 27. Ⱦɟɫɤɪɢɩɬɢɜɧɢ ɩɨɞɚɰɢ ɢ ɪɟɡɭɥɬɚɬɢ ɬɟɫɬɢɪɚʃɚ uKIM-1(ng/mgUcr) ɭ ɝɪɭɩɢ ɡɞɪɚɜɢɯ ɢ uKIM-1 (ng/mgUcr) ɩɨ ɦɟɪɟʃɢɦɚ (ɢɧɢɰɢʁɚɥɧɨ, I ɢ II ɩɨɫɬɨɩ. ɤɨɧɬɪɨɥɚ) ɭ ɝɪɭɩɢ ɨɛɨɥɟɥɢɯ ɉɚɪɨɜɢ ɦɟɪɟʃɚ uKIM-1 (ng/ml) Ⱦɟɫɤɪɢɩɬɢɜɧɢ ɩɨɞɚɰɢ Wilcoxon signed rank ɬɟɫɬ with continuity correction N ɉɪɨɫɟɤ (ɋȾ) Ɇɟɞɢʁɚɧɚ (ɨɩɫɟɝ) Ɂɞɪɚɜɢ vs 40 0.23 (0.15) 0.18 (0.043-0.604) V= 250 p= 0.0015 Ȼɨɥɟɫɧɢ (ɢɧɢцɢјɚɥɧɚ ɜ.) 40 0.9 (1.84) 0.364 (0.076-9.8) Ɂɞɪɚɜɢ vs 40 0.23 (0.15) 0.18 (0.043-0.604) V= 305 p= 0.056 Ȼɨɥɟɫɧɢ (I ɩɨɫɬɨɩ. ɤɨɧ.) 36 0.33 (0.22) 0.278 (0.072-0.814) Ɂɞɪɚɜɢ vs 40 0.23 (0.15) 0.18 (0.043-0.604) V= 323.5 p= 0.194 Ȼɨɥɟɫɧɢ (II ɩɨɫɬɨɩ. ɤɨɧ.) 22 0.17 (0.1) 0.150 (0.05-0.456) Ʉɚɨ ɲɬɨ ɫɟ ɢɡ ɬɚɛɟɥɟ ɛɪ. 27. ɦɨɠɟ ɜɢɞɟɬɢ, ɢɧɢɰɢʁɚɥɧɚ ɜɪɟɞɧɨɫɬ ɤɨɪɢɝɨɜɚɧɟ ɤɨɧɰɟɧɬɪɚɰɢʁɟ uKIM-1(ng/mgUcr) ɭ ɝɪɭɩɢ ɨɛɨɥɟɥɢɯ ɫɬɚɬɢɫɬɢɱɤɢ ʁɟ ɡɧɚɱɚʁɧɨ ɜɢɲɚ ɭ ɨɞɧɨɫɭ ɧɚ ʃɟɧɭ ɜɪɟɞɧɨɫɬ ɭ ɝɪɭɩɢ ɡɞɪɚɜɢɯ (p=0.0015). ɇɚ ɩɪɜɨʁ ɩɨɫɬɨɩɟɪɚɬɢɜɧɨʁ ɤɨɧɬɪɨɥɢ ɜɪɟɞɧɨɫɬ uKIM- 1(ng/mgUcr) ɭ ɝɪɭɩɢ ɨɛɨɥɟɥɢɯ ɩɚɞɚ ɢ ɞɨɫɬɢɠɟ ɧɚʁɧɢɠɭ ɜɪɟɞɧɨɫɬ ɧɚ ɞɪɭɝɨʁ ɩɨɫɬɨɩɟɪɚɬɢɜɧɨʁ ɤɨɧɬɪɨɥɢ. ɇɚ ɩɪɜɨʁ ɢ ɞɪɭɝɨʁ ɩɨɫɬɨɩɟɪɚɬɢɜɧɨʁ ɤɨɧɬɪɨɥɢ ɧɟ ɩɨɫɬɨʁɢ ɫɬɚɬɢɫɬɢɱɤɢ ɡɧɚɱɚʁɧɚ ɪɚɡɥɢɤɚ ɢɡɦɟђɭ ɝɪɭɩɚ. ɇɚ ɝɪɚɮɢɤɨɧɭ ɛɪ. 2. ɩɪɢɤɚɡɚɧɟ ɫɭ ɜɪɟɞɧɨɫɬɢ ɤɨɪɢɝɨɜɚɧɟ ɤɨɧɰɟɧɬɪɚɰɢʁɟ uKIM-1 (ng/mgUcr) ɭ ɝɪɭɩɢ ɡɞɪɚɜɢɯ ɢ uKIM-1 (ng/mgUcr) ɩɨ ɦɟɪɟʃɢɦɚ (ɢɧɢɰɢʁɚɥɧɨ ɢɥɢ ɩɪɟɨɩɟɪɚɬɢɜɧɨ, ɩɪɜɚ ɢ ɞɪɭɝɚ ɩɨɫɬɨɩɟɪɚɬɢɜɧɚ ɤɨɧɬɪɨɥɚ) ɭ ɝɪɭɩɢ ɨɛɨɥɟɥɢɯ 0 0.2 0.4 0.6 0.8 1 1.2 K IM -1 ( n g /m l) ɊȿɁɍɅɌȺɌɂ 55 Ƚɪɚɮɢɤɨɧ ɛɪ. 2. ɉɪɢɤɚɡ uKIM-1 (ng/mgUcr) ɭ ɝɪɭɩɢ ɡɞɪɚɜɢɯ ɢ uKIM-1 (ng/mgUcr) ɩɨ ɦɟɪɟʃɢɦɚ (ɢɧɢɰɢʁɚɥɧɨ, I ɢ II ɩɨɫɬɨɩ. ɤɨɧɬɪɨɥɚ) ɭ ɝɪɭɩɢ ɨɛɨɥɟɥɢɯ Ɉɞ ɢɧɬɟɪɟɫɚ ɡɚ ɢɫɬɪɚɠɢɜɚʃɟ ɛɢɥɨ ʁɟ ɞɚ ɫɟ ɩɨɪɟɞɢ ɜɪɟɞɧɨɫɬ ɚɩɫɨɥɭɬɧɟ ɤɨɧɰɟɧɬɪɚɰɢʁɟ uKIM-1(ng/ml) ɩɪɟɦɚ ɤɚɬɟɝɨɪɢʁɢ ɜɟɥɢɱɢɧɟ ɬɭɦɨɪɚ ɭ ɝɪɭɩɢ ɨɛɨɥɟɥɢɯ ɢ ɭɪɢɧɚɪɧɟ ɤɨɧɰɟɧɬɪɚɰɢʁɟ KIM-1 ɭ ɝɪɭɩɢ ɡɞɪɚɜɢɯ. Ⱦɟɫɤɪɢɩɬɢɜɧɢ ɩɨɞɚɰɢ ɢ ɪɟɡɭɥɬɚɬɢ ɬɟɫɬɢɪɚʃɚ ɩɪɢɤɚɡɚɧɢ ɫɭ ɭ ɬɚɛɟɥɢ ɛɪ. 28. Ɍɚɛɟɥɚ ɛɪ. 28. Ⱦɟɫɤɪɢɩɬɢɜɧɢ ɩɨɞɚɰɢ ɢ ɪɟɡɭɥɬɚɬɢ ɬɟɫɬɢɪɚʃɚ uKIM-1(nР/ml) ɩɪɟɦɚ ɤɚɬɟɝɨɪɢʁɢ ɜɟɥɢɱɢɧɟ ɬɭɦɨɪɚ ɭ ɝɪɭɩɢ ɨɛɨɥɟɥɢɯ ɢ uKIM-1(nР/ml)ɭ ɝɪɭɩɢ ɡɞɪɚɜɢɯ uKIM-1.0 Ɉɛɨɥɟɥɢ-ɤɚɬɟɝɨɪɢʁɟ ɜɟɥɢɱɢɧɟ ɬɭɦɨɪɚ Ɂɞɪɚɜɢ Kruskal- Wallis-ɨɜ ɬɟɫɬ ≤4МЦ (1) 4.1-7 cm (2) >7 cm (3) N (100%) 18 (100%) 10 (90%) 12 (100%) 40 (100%) ɉɪɨɫɟɤ (ɋȾ) 0.46 (0.59) 0.52 (0.6) 2.28 (2.13) 0.14 (0.08) χ22=28.74; p= 2.53*10-6 Ɇɟɞɢʁɚɧɚ (ɨɩɫɟɝ) 0.29 (0.038-2.1) 0.24 (0.075-2) 1 (0.147-5) 0.12 (0.036-0.281) Ȼɟɡ ɩɨɞɚɬɚɤɚ - 1 (10%) - - Ʉɚɨ ɲɬɨ ɫɟ ɢɡ ɬɚɛɟɥɟ ɛɪ. 28. ɜɢɞɢ, ɩɨɫɬɨʁɢ ɫɬɚɬɢɫɬɢɱɤɢ ɡɧɚɱɚʁɧɚ ɪɚɡɥɢɤɚ ɢɡɦɟђɭ ɜɪɟɞɧɨɫɬɢ uKIM-1(ng/ml) ɩɪɟɦɚ ɤɚɬɟɝɨɪɢʁɢ ɜɟɥɢɱɢɧɟ ɬɭɦɨɪɚ ɭ ɝɪɭɩɢ ɨɛɨɥɟɥɢɯ ɢ uKIM-1(ng/ml) ɭ ɝɪɭɩɢ ɡɞɪɚɜɢɯ (p=2.53*10-6). Ⱦɨɞɚɬɧɢɦ ɬɟɫɬɢɪɚʃɟɦ ɩɚɪɨɜɚ ɡɞɪɚɜɢ ɫɚ ɤɚɬɟɝɨɪɢʁɚɦɚ ɜɟɥɢɱɢɧɟ ɬɭɦɨɪɚ ɭ ɝɪɭɩɢ ɨɛɨɥɟɥɢɯ, ɞɨɛɢʁɟɧɢ ɩɨɞɚɰɢ ɫɭ ɩɪɢɤɚɡɚɧɢ ɭ ɬɚɛɟɥɢ ɛɪ. 29. 0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 K IM -1 ( n g /m g U cr ) ɊȿɁɍɅɌȺɌɂ 56 Ɍɚɛɟɥɚ ɛɪ. 29. Ɋɟɡɭɥɬɚɬɢ ɬɟɫɬɢɪɚʃɚ ɜɪɟɞɧɨɫɬɢ uKIM-1.0 (nР/ml) ɩɨ ɩɚɪɨɜɢɦɚ ɡɞɪɚɜɢ ɢ ɤɚɬɟɝɨɪɢʁɟ ɜɟɥɢɱɢɧɟ ɬɭɦɨɪɚ ɭ ɝɪɭɩɢ ɨɛɨɥɟɥɢɯ ɉɚɪɨɜɢ ɤɚɬɟɝɨɪɢʁɚ ɜɟɥ. ɬɭɦɨɪɚ ɢ ɡɞɪɚɜɢ Wilcox rank sum test with continuity correction ≤4 cm vs ɡɞɪɚɜɢ W= 336.5; p*= 0.002 4.1-7 cm vs ɡɞɪɚɜɢ W= 193; p*= 0.006 > 7cm vs ɡɞɪɚɜɢ W= 280 ; p*= 5.342*10-6 *Bonferroni korekcija: 0.05/3=0.0167 Ʉɚɨ ɲɬɨ ɫɟ ɜɢɞɢ ɢɡ ɬɚɛɟɥɚ ɛɪ. 28. ɢ 29. ɜɢɞɢ, ɜɪɟɞɧɨɫɬ ɚɩɫɨɥɭɬɧɟ ɤɨɧɰɟɧɬɪɚɰɢʁɟ uKIM- 1(ng/ml) ɭ ɫɜɢɦ ɤɚɬɟɝɨɪɢʁɚɦɚ ɜɟɥɢɱɢɧɟ ɬɭɦɨɪɚ ɭ ɝɪɭɩɢ ɨɛɨɥɟɥɢɯ, ɫɬɚɬɢɫɬɢɱɤɢ ʁɟ ɡɧɚɱɚʁɧɨ ɜɟʄɚ ɭ ɨɞɧɨɫɭ ɧɚ ɜɪɟɞɧɨɫɬ uKIM-1(ng/ml) ɭ ɝɪɭɩɢ ɡɞɪɚɜɢɯ. ɂɫɬɢ ɨɛɥɢɤ ɩɨɪɟђɟʃɚ ɫɩɪɨɜɟɞɟɧ ʁɟ ɢ ɡɚ ɜɪɟɞɧɨɫɬ ɤɨɪɢɝɨɜɚɧɟ ɤɨɧɰɟɧɬɪɚɰɢʁɟ uKIM- 1(ng/mgUcr). Ɍɚɛɟɥɚ ɛɪ. 30. Ⱦɟɫɤɪɢɩɬɢɜɧɢ ɩɨɞɚɰɢ ɢ ɪɟɡɭɥɬɚɬɢ ɬɟɫɬɢɪɚʃɚ uKIM-1(ng/mgUcr) ɩɪɟɦɚ ɤɚɬɟɝɨɪɢʁɢ ɜɟɥɢɱɢɧɟ ɬɭɦɨɪɚ ɭ ɝɪɭɩɢ ɨɛɨɥɟɥɢɯ ɢ uKIM-1(ng/mgUcr) ɭ ɝɪɭɩɢ ɡɞɪɚɜɢɯ uKIM-1 Ɉɛɨɥɟɥɢ-ɤɚɬɟɝɨɪɢʁɟ ɜɟɥɢɱɢɧɟ ɬɭɦɨɪɚ Ɂɞɪɚɜɢ Kruskal- Wallis-ɨɜ ɬɟɫɬ ≤4МЦ (1) 4.1-7 cm (2) >7 cm (3) N (%) 18 (100%) 10 (100%) 12 (100%) 40 (100%) ɉɪɨɫɟɤ (ɋȾ) 0.37 (0.32) 0.28 (0.16) 2.2 (3.02) 0.23 (0.15) χ22=28.57; p= 8.03*10-5 Ɇɟɞɢʁɚɧɚ (ɨɩɫɟɝ) 0.28 (0.109-1.40) 0.22 (0.076-0.56) 0.66 (0.34-9.8) 0.18 (0.04-0.604) Ȼɟɡ ɩɨɞɚɬɚɤɚ - 1 (10%) - - Ʉɚɨ ɲɬɨ ɫɟ ɢɡ ɬɚɛɟɥɟ ɛɪ. 30. ɜɢɞɢ, ɩɨɫɬɨʁɢ ɫɬɚɬɢɫɬɢɱɤɢ ɡɧɚɱɚʁɧɚ ɪɚɡɥɢɤɚ ɢɡɦɟђɭ ɜɪɟɞɧɨɫɬɢ ɤɨɪɢɝɨɜɚɧɟ ɤɨɧɰɟɧɬɪɚɰɢʁɟ uKIM-1(ng/mgUcr) ɩɪɟɦɚ ɤɚɬɟɝɨɪɢʁɢ ɜɟɥɢɱɢɧɟ ɬɭɦɨɪɚ ɭ ɝɪɭɩɢ ɨɛɨɥɟɥɢɯ ɢ uKIM-1(ng/mgUcr) ɭ ɝɪɭɩɢ ɡɞɪɚɜɢɯ (p=8.03*10-5). Ⱦɨɞɚɬɧɢɦ ɬɟɫɬɢɪɚʃɟɦ ɩɚɪɨɜɚ ɡɞɪɚɜɢ ɫɚ ɤɚɬɟɝɨɪɢʁɚɦɚ ɜɟɥɢɱɢɧɟ ɬɭɦɨɪɚ ɭ ɝɪɭɩɢ ɨɛɨɥɟɥɢɯ, ɞɨɛɢʁɟɧɢ ɩɨɞɚɰɢ ɫɭ ɩɪɢɤɚɡɚɧɢ ɭ ɬɚɛɟɥɢ ɛɪ. 31. Ɍɚɛɟɥɚ ɛɪ. 31. Ɋɟɡɭɥɬɚɬɢ ɬɟɫɬɢɪɚʃɚ ɜɪɟɞɧɨɫɬɢ uKIM-1.0 (ng/mgUcr) ɩɨ ɩɚɪɨɜɢɦɚ ɡɞɪɚɜɢ ɢ ɤɚɬɟɝɨɪɢʁɚ ɜɟɥɢɱɢɧɟ ɬɭɦɨɪɚ ɭ ɝɪɭɩɢ ɨɛɨɥɟɥɢɯ ɉɚɪɨɜɢ ɤɚɬɟɝɨɪɢʁɚ ɜɟɥ. ɬɭɦɨɪɚ ɢ ɡɞɪɚɜɢ Wilcox rank sum test with continuity correction ≤4 cm vs ɡɞɪɚɜɢ W= 291; p*= 0.058 4.1-7 cm vs ɡɞɪɚɜɢ W= 150; p*= 0.270 > 7cm vs ɡɞɪɚɜɢ W= 269; p*= 3.215*10-6 *Bonferroni korekcija: 0.05/3=0.0167 Ʉɚɨ ɲɬɨ ɫɟ ɢɡ ɬɚɛɟɥɚ ɛɪ. 30. ɢ 31.ɜɢɞɢ, ɩɪɟɨɩɟɪɚɬɢɜɧɚ ɜɪɟɞɧɨɫɬ ɤɨɪɢɝɨɜɚɧɟ ɤɨɧɰɟɧɬɪɚɰɢʁɟ uKIM-1.0 (ng/mgUcr) ɜɟʄɚ ʁɟ ɭ ɫɜɢɦ ɤɚɬɟɝɨɪɢʁɚɦɚ ɜɟɥɢɱɢɧɟ ɬɭɦɨɪɚ ɭ ɝɪɭɩɢ ɨɛɨɥɟɥɢɯ ɭ ɊȿɁɍɅɌȺɌɂ 57 ɨɞɧɨɫɭ ɧɚ ɜɪɟɞɧɨɫɬ ɤɨɪɢɝɨɜɚɧɟ ɤɨɧɰɟɧɬɪɚɰɢʁɟ uKIM-1.0 (ng/mgUcr) ɭ ɝɪɭɩɢ ɡɞɪɚɜɢɯ, ɚɥɢ ʁɟ ɫɬɚɬɢɫɬɢɫɬɢɱɤɢ ɡɧɚɱɚʁɧɨ ɜɢɲɚ ɬɟɤ ɭ ɤɚɬɟɝɨɪɢʁɢ ɬɭɦɨɪɚ ɜɟʄɢɯ ɨɞ 7 cm. 4.3.2. Ʉɨɦɩɚɪɚɰɢʁɚ ɭɪɢɧɚɪɧɟ ɤɨɧɰɟɧɬɪɚɰɢʁɟ AQP-1 ɢɡɦɟђɭ ɢɫɩɢɬɢɜɚɧɢɯ ɝɪɭɩɚ ɍ ɢɫɬɪɚɠɢɜɚʃɭ ʁɟ ɫɩɪɨɜɟɞɟɧɨ ɩɨɪɟђɟʃɟ ɜɪɟɞɧɨɫɬɢ ɚɩɫɨɥɭɬɧɟ ɤɨɧɰɟɧɬɪɚɰɢʁɟ uAQP-1 (ng/ml) ɭ ɝɪɭɩɢ ɡɞɪɚɜɢɯ ɢ uAQP-1 (ng/ml) ɩɨ ɦɟɪɟʃɢɦɚ (ɢɧɢɰɢʁɚɥɧɨ ɬʁ. ɩɪɟɨɩɟɪɚɬɢɜɧɨ, ɩɪɜɚ ɢ ɞɪɭɝɚ ɩɨɫɬɨɩɟɪɚɬɢɜɧɚ ɤɨɧɬɪɨɥɚ) ɭ ɝɪɭɩɢ ɨɛɨɥɟɥɢɯ. Ⱦɟɫɤɪɢɩɬɢɜɧɢ ɩɨɞɚɰɢ ɢ ɪɟɡɭɥɬɚɬɢ ɬɟɫɬɢɪɚʃɚ ɩɪɢɤɚɡɚɧɢ ɫɭ ɭ ɬɚɛɟɥɢ ɛɪ. 32. Ɍɚɛɟɥɚɛɪ. 32. Ⱦɟɫɤɪɢɩɬɢɜɧɢ ɩɨɞɚɰɢ ɢ ɪɟɡɭɥɬɚɬɢ ɬɟɫɬɢɪɚʃɚ uAQP1 (nР/ml) ɭ ɝɪɭɩɢ ɡɞɪɚɜɢɯ ɢ uAQP1 (nР/ml) ɩɨ ɦɟɪɟʃɢɦɚ (ɢɧɢɰɢʁɚɥɧɨ, I ɢ II ɩɨɫɬɨɩ. ɤɨɧɬɪɨɥɚ) ɭ ɝɪɭɩɢ ɨɛɨɥɟɥɢɯ ɉɚɪɨɜɢ ɦɟɪɟʃɚ uAQP1 (ng/ml) Ⱦɟɫɤɪɢɩɬɢɜɧɢ ɩɨɞɚɰɢ Wilcoxon signed rank ɬɟɫɬ with continuity correction N ɉɪɨɫɟɤ (ЋD) Ɇɟɞɢʁɚɧɚ (ɨɩɫɟɝ) Ɂɞɪɚɜɢ vs 40 0.09 (0.05) 0.088 (0-0.27) V= 465 p= 0.9717 Ȼɨɥɟɫɧɢ (ɢɧɢцɢјɚɥɧɚ ɜ.) 39 0.1 (0.04) 0.086 (0-0.287) Ɂɞɪɚɜɢ vs 40 0.09 (0.05) 0.088 (0-0.27) V= 362 p= 0.2285 Ȼɨɥɟɫɧɢ (I ɩɨɫɬɨɩ. ɤɨɧ.) 37 0.1 (0.03) 0.091 (0-0.149) Ɂɞɪɚɜɢ vs 40 0.09 (0.05) 0.088 (0-0.27) V= 306 p= 0.5297 Ȼɨɥɟɫɧɢ (II ɩɨɫɬɨɩ. ɤɨɧ.) 23 0.08 (0.04) 0.083 (0-0.211) ɂɡ ɬɚɛɟɥɟ ɛɪ. 32. ɫɟ ɜɢɞɢ ɞɚ ɧɟ ɩɨɫɬɨʁɢ ɫɬɚɬɢɫɬɢɱɤɢ ɡɧɚɱɚʁɧɚ ɪɚɡɥɢɤɚ ɭ ɜɪɟɞɧɨɫɬɢ uAQP1 (ng/ml) ɢ ɬɨ ɤɚɤɨ ɢɧɢɰɢʁɚɥɧɢɯ, ɬɚɤɨ ɢ ɜɪɟɞɧɨɫɬɢ ɧɚ ɩɪɜɨʁ ɢ ɞɪɭɝɨʁ ɩɨɫɬɨɩɟɪɚɬɢɜɧɨʁ ɤɨɧɬɪɨɥɢ ɭ ɝɪɭɩɢ ɨɛɨɥɟɥɢɯ ɭ ɨɞɧɨɫɭ ɧɚ ɜɪɟɞɧɨɫɬɢ uAQP1 (ng/ml) ɭ ɝɪɭɩɢ ɡɞɪɚɜɢɯ. ɂɫɬɢ ɜɢɞ ɬɟɫɬɢɪɚʃɚ ɢɡɦɟђɭ ɝɪɭɩɟ ɡɞɪɚɜɢɯ ɢ ɝɪɭɩɟ ɨɛɨɥɟɥɢɯ ɫɩɪɨɜɟɞɟɧ ʁɟ ɢ ɡɚ ɤɨɪɢɝɨɜɚɧɭ ɜɪɟɞɧɨɫɬ uAQP1 (ng/mgUcr). Ⱦɟɫɤɪɢɩɬɢɜɧɢ ɩɨɞɚɰɢ ɢ ɪɟɡɭɥɬɚɬɢ ɬɟɫɬɢɪɚʃɚ ɢ ɩɪɢɤɚɡɚɧɢ ɫɭ ɭ ɬɚɛɟɥɢ ɛɪ. 33. Ɍɚɛɟɥɚ ɛɪ. 33. Ⱦɟɫɤɪɢɩɬɢɜɧɢ ɩɨɞɚɰɢ ɢ ɪɟɡɭɥɬɚɬɢ ɬɟɫɬɢɪɚʃɚ uAQP1 (ng/mgUcr) ɭ ɝɪɭɩɢ ɡɞɪɚɜɢɯ ɢ uAQP1 (ng/mgUcr) ɩɨ ɦɟɪɟʃɢɦɚ (ɢɧɢɰɢʁɚɥɧɨ, I ɢ II ɩɨɫɬɨɩ. ɤɨɧɬɪɨɥɚ) ɭ ɝɪɭɩɢ ɨɛɨɥɟɥɢɯ ɉɚɪɨɜɢ ɦɟɪɟʃɚ uAQP1 (ng/mgUcr) Ⱦɟɫɤɪɢɩɬɢɜɧɢ ɩɨɞɚɰɢ Wilcoxon signed rank ɬɟɫɬ with continuity correction N ɉɪɨɫɟɤ (ЋD) Ɇɟɞɢʁɚɧɚ (ɨɩɫɟɝ) Ɂɞɪɚɜɢ vs 40 0.18 (0.16) 0.140 (0-0.717) V= 621 p= 0.0309 Ȼɨɥɟɫɧɢ (ɢɧɢцɢјɚɥɧɚ ɜ.) 39 0.11 (0.09) 0.079 (0-0.412) Ɂɞɪɚɜɢ vs 40 0.18 (0.16) 0.140 (0-0.717) V= 490 p= 0.3855 Ȼɨɥɟɫɧɢ (I ɩɨɫɬɨɩ. ɤɨɧ.) 36 0.15 (0.16) 0.104 (0-0.925) Ɂɞɪɚɜɢ vs 40 0.18 (0.16) 0.140 (0-0.717) V= 256.5 p= 0.6858 Ȼɨɥɟɫɧɢ (II ɩɨɫɬɨɩ. ɤɨɧ.) 23 0.2 (0.2) 0.166 (0-0.79) ɊȿɁɍɅɌȺɌɂ 58 Ʉɚɨ ɲɬɨ ɫɟ ɢɡ ɬɚɛɟɥɟ ɛɪ. 33. ɦɨɠɟ ɜɢɞɟɬɢ, ɢɧɢɰɢʁɚɥɧɚ ɜɪɟɞɧɨɫɬ ɤɨɪɢɝɨɜɚɧɟ ɤɨɧɰɟɧɬɪɚɰɢʁɟ uAQP1 (ng/mgUcr)ɭ ɝɪɭɩɢ ɨɛɨɥɟɥɢɯ ɫɬɚɬɢɫɬɢɱɤɢ ʁɟ ɡɧɚɱɚʁɧɨ ɧɢɠɚ ɭ ɨɞɧɨɫɭ ɧɚ ʃɟɧɭ ɜɪɟɞɧɨɫɬ ɭ ɝɪɭɩɢ ɡɞɪɚɜɢɯ (p=0.031). ɇɚ ɩɪɜɨʁ ɩɨɫɬɨɩɟɪɚɬɢɜɧɨʁ ɤɨɧɬɪɨɥɢ ɜɪɟɞɧɨɫɬ uAQP1 (ng/mgUcr)ɭ ɝɪɭɩɢ ɨɛɨɥɟɥɢɯ ɪɚɫɬɟ ɢ ɞɨɫɬɢɠɟ ɧɚʁɜɢɲɭ ɜɪɟɞɧɨɫɬ ɧɚ ɞɪɭɝɨʁ ɩɨɫɬɨɩɟɪɚɬɢɜɧɨʁ ɤɨɧɬɪɨɥɢ, ɩɪɢ ɱɟɦɭ ɧɚ ɩɪɜɨʁ ɢ ɞɪɭɝɨʁ ɩɨɫɬɨɩɟɪɚɬɢɜɧɨʁ ɤɨɧɬɪɨɥɢ ɧɟ ɩɨɫɬɨʁɢ ɫɬɚɬɢɫɬɢɱɤɢ ɡɧɚɱɚʁɧɚ ɪɚɡɥɢɤɚ ɭ ɜɪɟɞɧɨɫɬɢ uAQP1 (ng/mgUcr) ɢɡɦɟђɭ ɝɪɭɩɚ. Ɉɞ ɢɧɬɟɪɟɫɚ ɡɚ ɢɫɬɪɚɠɢɜɚʃɟ ɛɢɥɨ ʁɟ ɞɚ ɫɟ ɩɨɪɟɞɢ ɩɪɟɨɩɟɪɚɬɢɜɧɚ ɜɪɟɞɧɨɫɬ ɚɩɫɨɥɭɬɧɟ ɤɨɧɰɟɧɬɪɚɰɢʁɟ uAQP-1.0(ng/ml) ɩɪɟɦɚ ɤɚɬɟɝɨɪɢʁɢ ɜɟɥɢɱɢɧɟ ɬɭɦɨɪɚ ɭ ɝɪɭɩɢ ɨɛɨɥɟɥɢɯ ɢ ɭɪɢɧɚɪɧɟ ɤɨɧɰɟɧɬɪɚɰɢʁɟ AQP-1(ng/ml)ɭ ɝɪɭɩɢ ɡɞɪɚɜɢɯ. Ⱦɟɫɤɪɢɩɬɢɜɧɢ ɩɨɞɚɰɢ ɢ ɪɟɡɭɥɬɚɬɢ ɬɟɫɬɢɪɚʃɚ ɩɪɢɤɚɡɚɧɢ ɫɭ ɭ ɬɚɛɟɥɢ ɛɪ. 34. Ɍɚɛɟɥɚ ɛɪ. 34. Ⱦɟɫɤɪɢɩɬɢɜɧɢ ɩɨɞɚɰɢ ɢ ɪɟɡɭɥɬɚɬɢ ɬɟɫɬɢɪɚʃɚ uAQP-1.0 (nР/ml) ɩɪɟɦɚ ɤɚɬɟɝɨɪɢʁɢ ɜɟɥɢɱɢɧɟ ɬɭɦɨɪɚ ɭ ɝɪɭɩɢ ɨɛɨɥɟɥɢɯ ɢ uAQP-1 (nР/ml) ɭ ɝɪɭɩɢ ɡɞɪɚɜɢɯ uAQP-1.0 Ɉɛɨɥɟɥɢ-ɤɚɬɟɝɨɪɢʁɟ ɜɟɥɢɱɢɧɟ ɬɭɦɨɪɚ Ɂɞɪɚɜɢ Kruskal- Wallis-ɨɜ ɬɟɫɬ ≤4МЦ (1) 4.1-7 cm (2) >7 cm (3) N (%) 17 (94.12%) 10 (90%) 12 (100%) 40 (100%) ɉɪɨɫɟɤ (ɋȾ) 0.1 (0.06) 0.08 (0.03) 0.1 (0.04) 0.09 (0.05) χ22=0.995; p= 0.8023 Ɇɟɞɢʁɚɧɚ (ɨɩɫɟɝ) 0.085 (0.073-0.287) 0.087 (0-0.097) 0.087 (0.077-0.207) 0.088 (0-0.207) Ȼɟɡ ɩɨɞɚɬɚɤɚ 1 (5.88%) 1 (10%) - - Ʉɚɨ ɲɬɨ ɫɟ ɢɡ ɬɚɛɟɥɟ ɛɪ. 34. ɜɢɞɢ, ɧɟ ɩɨɫɬɨʁɢ ɫɬɚɬɢɫɬɢɱɤɢ ɡɧɚɱɚʁɧɚ ɪɚɡɥɢɤɚ ɢɡɦɟђɭ ɩɪɟɨɩɟɪɚɬɢɜɧɢɯ ɜɪɟɞɧɨɫɬɢ uAQP-1 (ng/ml) ɩɪɟɦɚ ɤɚɬɟɝɨɪɢʁɢ ɜɟɥɢɱɢɧɟ ɬɭɦɨɪɚ ɭ ɝɪɭɩɢ ɨɛɨɥɟɥɢɯ ɢuAQP-1(ng/ml) ɭ ɝɪɭɩɢ ɡɞɪɚɜɢɯ. Ⱦɨɞɚɬɧɢɦ ɬɟɫɬɢɪɚʃɟɦ ɩɚɪɨɜɚ ɡɞɪɚɜɢ ɫɚɤɚɬɟɝɨɪɢʁɚɦɚ ɜɟɥɢɱɢɧɟ ɬɭɦɨɪɚ ɭ ɝɪɭɩɢ ɨɛɨɥɟɥɢɯ, ɞɨɛɢʁɟɧɢ ɩɨɞɚɰɢ ɫɭ ɩɪɢɤɚɡɚɧɢ ɭ ɬɚɛɟɥɢ ɛɪ. 35. Ɍɚɛɟɥɚ ɛɪ. 35. Ɋɟɡɭɥɬɚɬɢ ɬɟɫɬɢɪɚʃɚ ɜɪɟɞɧɨɫɬɢ uAQP-1.0 (nР/ml) ɩɨ ɩɚɪɨɜɢɦɚ ɡɞɪɚɜɢ ɢ ɤɚɬɟɝɨɪɢʁɟ ɜɟɥɢɱɢɧɟ ɬɭɦɨɪɚ ɭ ɝɪɭɩɢ ɨɛɨɥɟɥɢɯ ɉɚɪɨɜɢ ɤɚɬɟɝɨɪɢʁɚ ɜɟɥ. ɬɭɦɨɪɚ ɢ ɡɞɪɚɜɢ Wilcox rank sum test with continuity correction ≤4 cm vs ɡɞɪɚɜɢ W=211; p*= 0.863 4.1-7 cm vs ɡɞɪɚɜɢ W= 102; p*= 0.508 > 7cm vs ɡɞɪɚɜɢ W= 158 ; p*= 0.650 *Bonferroni korekcija: 0.05/3=0.0167 Ʉɚɨ ɲɬɨ ɫɟ ɜɢɞɢ ɢɡ ɬɚɛɟɥɚ ɛɪ. 34. ɢ 35., ɧɟ ɩɨɫɬɨʁɢ ɫɬɚɬɢɫɬɢɱɤɢ ɡɧɚɱɚʁɧɚ ɪɚɡɥɢɤɚ ɭ ɩɪɟɨɩɟɪɚɬɢɜɧɨʁ ɜɪɟɞɧɨɫɬɢ ɚɩɫɨɥɭɬɧɟ ɤɨɧɰɟɧɬɪɚɰɢʁɟ uAQP-1(ng/ml) ɧɢ ɭ ʁɟɞɧɨʁ ɨɞ ɤɚɬɟɝɨɪɢʁɚ ɜɟɥɢɱɢɧɟ ɬɭɦɨɪɚ ɭ ɝɪɭɩɢ ɨɛɨɥɟɥɢɯ ɭ ɨɞɧɨɫɭ ɧɚ ɜɪɟɞɧɨɫɬ uAQP-1(ng/ml) ɭ ɝɪɭɩɢ ɡɞɪɚɜɢɯ. ɊȿɁɍɅɌȺɌɂ 59 Ⱦɟɫɤɪɢɩɬɢɜɧɢ ɩɨɞɚɰɢ ɢ ɪɟɡɭɥɬɚɬɢ ɬɟɫɬɢɪɚʃɚ ɡɚ ɩɪɟɨɩɟɪɚɬɢɜɧɭ ɤɨɪɢɝɨɜɚɧɭ ɜɪɟɞɧɨɫɬ ɤɨɧɰɟɧɬɪɚɰɢʁɟ uAQP-1.0 (ng/mgUcr) ɩɪɟɦɚ ɤɚɬɟɝɨɪɢʁɢ ɜɟɥɢɱɢɧɟ ɬɭɦɨɪɚ ɭ ɝɪɭɩɢ ɨɛɨɥɟɥɢɯ ɢ ɭɪɢɧɚɪɧɟ ɤɨɧɰɟɧɬɪɚɰɢʁɟ AQP-1(ng/mgUcr) ɭ ɝɪɭɩɢ ɡɞɪɚɜɢɯ ɩɪɢɤɚɡɚɧɢ ɫɭ ɭ ɬɚɛɟɥɢ ɛɪ. 36. Ɍɚɛɟɥɚ ɛɪ. 36. Ⱦɟɫɤɪɢɩɬɢɜɧɢ ɩɨɞɚɰɢ ɢ ɪɟɡɭɥɬɚɬɢ ɬɟɫɬɢɪɚʃɚ uAQP-1.0 (ng/mgUcr) ɩɪɟɦɚ ɤɚɬɟɝɨɪɢʁɢ ɜɟɥɢɱɢɧɟ ɬɭɦɨɪɚ ɭ ɝɪɭɩɢ ɨɛɨɥɟɥɢɯ ɢ uAQP-1 (ng/mgUcr) ɭ ɝɪɭɩɢ ɡɞɪɚɜɢɯ uAQP-1.0 Ɉɛɨɥɟɥɢ-ɤɚɬɟɝɨɪɢʁɟ ɜɟɥɢɱɢɧɟ ɬɭɦɨɪɚ Ɂɞɪɚɜɢ Kruskal- Wallis-ɨɜ ɬɟɫɬ ≤4МЦ (1) 4.1-7 cm (2) >7 cm (3) N (%) 17 (100%) 10 (100%) 12 (100%) 40 (100%) ɉɪɨɫɟɤ (ɋȾ) 0.14 (0.12) 0.07 (0.04) 0.1 (0.07) 0.18 (0.16) χ22=7.47; p= 0.058 Ɇɟɞɢʁɚɧɚ (ɨɩɫɟɝ) 0.093 (0.023-0.412) 0.062 (0-0.144) 0.077 (0.037-0.248) 0.140 (0-0.717) Ȼɟɡ ɩɨɞɚɬɚɤɚ 1 (6%) 1 (10%) - - Ʉɚɨ ɲɬɨ ɫɟ ɢɡ ɬɚɛɟɥɟ ɛɪ. 36. ɜɢɞɢ, ɜɪɟɞɧɨɫɬuAQP-1(ng/mgUcr) ɭ ɝɪɭɩɢ ɡɞɪɚɜɢɯ ʁɟ ɜɢɲɚ ɭ ɨɞɧɨɫɭ ɧɚ ɩɪɟɨɩɟɪɚɬɢɜɧɭ ɜɪɟɞɧɨɫɬ uAQP-1(ng/mgUcr) ɭ ɫɜɟ ɬɪɢ ɤɚɬɟɝɨɪɢʁɟ ɜɟɥɢɱɢɧɟ ɬɭɦɨɪɚ ɭ ɝɪɭɩɢ ɨɛɨɥɟɥɢɯ, ɚɥɢ ɛɟɡ ɫɬɚɬɢɫɬɢɱɤɟ ɡɧɚɱɚʁɧɨɫɬɢ. Ⱦɨɞɚɬɧɢɦ ɬɟɫɬɢɪɚʃɟɦ ɩɚɪɨɜɚ ɡɞɪɚɜɢ ɫɚ ɤɚɬɟɝɨɪɢʁɚɦɚ ɜɟɥɢɱɢɧɟ ɬɭɦɨɪɚ ɭ ɝɪɭɩɢ ɨɛɨɥɟɥɢɯ, ɞɨɛɢʁɟɧɢ ɩɨɞɚɰɢ ɫɭ ɩɪɢɤɚɡɚɧɢ ɭ ɬɚɛɟɥɢ ɛɪ. 37. Ɍɚɛɟɥɚ ɛɪ. 37. Ɋɟɡɭɥɬɚɬɢ ɬɟɫɬɢɪɚʃɚ ɜɪɟɞɧɨɫɬɢ uAQP-1(ng/mgUcr) ɩɨ ɩɚɪɨɜɢɦɚ ɡɞɪɚɜɢ ɢ ɤɚɬɟɝɨɪɢʁɟ ɜɟɥɢɱɢɧɟ ɬɭɦɨɪɚ ɭ ɝɪɭɩɢ ɨɛɨɥɟɥɢɯ ɉɚɪɨɜɢ ɤɚɬɟɝɨɪɢʁɚ ɜɟɥ. ɬɭɦɨɪɚ ɢ ɡɞɪɚɜɢ Wilcox rank sum test with continuity correction ≤4 cm vs ɡɞɪɚɜɢ W=171; p*= 0.389 4.1-7 cm vs ɡɞɪɚɜɢ W= 55.5; p*= 0.015 > 7cm vs ɡɞɪɚɜɢ W= 88.5 ; p*= 0.065 *Bonferroni korekcija: 0.05/3=0.0167 Ʉɚɨ ɲɬɨ ɫɟ ɢɡ ɬɚɛɟɥɟ ɛɪ. 37. ɜɢɞɢ, ɩɨɫɬɨʁɢ ɫɬɚɬɢɫɬɢɱɤɢ ɡɧɚɱɚʁɧɚ ɪɚɡɥɢɤɚ ɭ ɜɪɟɞɧɨɫɬɢ ɩɪɟɨɩɟɪɚɬɢɜɧɟ ɤɨɪɢɝɨɜɚɧɟ ɤɨɧɰɟɧɬɪɚɰɢʁɟ uAQP-1 ɢɡɦɟђɭ ɡɞɪɚɜɢɯ ɢ ɤɚɬɟɝɨɪɢʁɟ ɜɟɥɢɱɢɧɟ ɬɭɦɨɪɚ 4.1-7 cm (p*= 0.015). 4.4. Ʉɨɦɩɚɪɚɰɢʁɚ ɩɪɟɨɩɟɪɚɬɢɜɧɢɯ ɜɪɟɞɧɨɫɬɢ uKIM-1 ɢ uAQP-1 ɢ ɩɚɬɨɯɢɫɬɨɥɨɲɤɢɯ ɤɚɪɚɤɬɟɪɢɫɬɢɤɚ ɬɭɦɨɪɚ ɭ ɝɪɭɩɢ ɨɛɨɥɟɥɢɯ 4.4.1. Ʉɨɦɩɚɪɚɰɢʁɚ ɩɪɟɨɩɟɪɚɬɢɜɧɢɯ ɜɪɟɞɧɨɫɬɢ uKIM-1 ɢ ɩɚɬɨɯɢɫɬɨɥɨɲɤɢɯ ɤɚɪɚɤɬɟɪɢɫɬɢɤɚ ɬɭɦɨɪɚ ɍ ɬɚɛɟɥɢ ɛɪ. 38. ɧɚɜɟɞɟɧɢ ɫɭ ɞɟɫɤɪɢɩɬɢɜɧɢ ɩɨɞɚɰɢ ɢ ɪɟɡɭɥɬɚɬɢ ɬɟɫɬɢɪɚʃɚ ɜɪɟɞɧɨɫɬɢ ɜɟɥɢɱɢɧɟ ɬɭɦɨɪɚ (cm) ɢ ɜɪɟɞɧɨɫɬɢ ɚɩɫɨɥɭɬɧɟ ɤɨɧɰɟɧɬɪɚɰɢʁɟ uKIM-1(ng/ml) ɭ ɝɪɭɩɢ ɨɛɨɥɟɥɢɯ. ɊȿɁɍɅɌȺɌɂ 60 Tɚɛɟɥɚ ɛɪ. 38. Ⱦɟɫɤɪɢɩɬɢɜɧɢ ɩɨɞɚɰɢ ɢ ɪɟɡɭɥɬɚɬɢ ɬɟɫɬɢɪɚʃɚ ɜɪɟɞɧɨɫɬɢ ɜɟɥɢɱɢɧɟ ɬɭɦɨɪɚ (cm) ɢ uKIM-1(ng/ml) ɉɚɪɚɦɟɬɪɢ Ⱦɟɫɤɪɢɩɬɢɜɧɢ ɩɨɞɚɰɢ Ɍɟɫɬ N ɉɪɨɫɟɤ (ɋȾ) Ɇɟɞɢʁɚɧɚ (ɨɩɫɟɝ) ȼɟɥɢɱɢɧɚ ɬɭɦɨɪɚ (cm) 41 5.46 (3.02) 4.3 (2-13) Spearman's rank correlation ρ=0.498; p =0.001 uKIM-1(ng/ml) 41 1.02 (1.49) 0.34 (0.038-5) ɂɡ ɬɚɛɟɥɟ ɛɪ. 38. ɫɟ ɜɢɞɢ ɞɚ ɩɨɫɬɨʁɢ ɫɬɚɬɢɫɬɢɱɤɢ ɡɧɚɱɚʁɧɚ ɩɨɡɢɬɢɜɧɚ ɭɦɟɪɟɧɚ ɤɨɪɟɥɚɰɢʁɚ ɢɡɦɟђɭ ɜɟɥɢɱɢɧɟ ɬɭɦɨɪɚ ɢ ɚɩɫɨɥɭɬɧɟ ɤɨɧɰɟɧɬɪɚɰɢʁɟ uKIM-1(ng/ml) (ρ=0.498), ɲɬɨ ɫɟ ɦɨɠɟ ɜɢɞɟɬɢ ɢ ɢɡ ɝɪɚɮɢɤɨɧɚ ɛɪ. 3. Ƚɪɚɮɢɤɨɧ ɛɪ.3. Кɨɪɟɥɚɰɢʁɚ ɜɟɥɢɱɢɧɟ ɬɭɦɨɪɚ ɢ ɚɩɫɨɥɭɬɧɟ ɩɪɟɨɩɟɪɚɬɢɜɧɟ ɤɨɧɰɟɧɬɪɚɰɢʁɟ uKIM-1(ng/ml) ɍ ɬɚɛɟɥɢ ɛɪ. 39. ɧɚɜɟɞɟɧɢ ɫɭ ɞɟɫɤɪɢɩɬɢɜɧɢ ɩɨɞɚɰɢ ɢ ɪɟɡɭɥɬɚɬɢ ɬɟɫɬɢɪɚʃɚ ɜɪɟɞɧɨɫɬɢ ɜɟɥɢɱɢɧɟ ɬɭɦɨɪɚ (cm) ɢ ɜɪɟɞɧɨɫɬɢ ɤɨɪɢɝɨɜɚɧɟ ɤɨɧɰɟɧɬɪɚɰɢʁɟ uKIM-1(ng/mgUcr) ɭ ɝɪɭɩɢ ɨɛɨɥɟɥɢɯ. y = 0.34664x - 0.86760 0 1 2 3 4 5 6 0 2 4 6 8 10 12 14 ȼɟɥɢɱɢɧɚ ɬɭɦɨɪɚ (МЦ) K IM - 1 (n g/ m l) ɊȿɁɍɅɌȺɌɂ 61 Tɚɛɟɥɚ ɛɪ. 39.Ⱦɟɫɤɪɢɩɬɢɜɧɢ ɩɨɞɚɰɢ ɢ ɪɟɡɭɥɬɚɬɢ ɬɟɫɬɢɪɚʃɚ ɜɪɟɞɧɨɫɬɢ ɜɟɥɢɱɢɧɟ ɬɭɦɨɪɚ (cm) ɢ uKIM-1(ng/mgUcr) ɉɚɪɚɦɟɬɪɢ Ⱦɟɫɤɪɢɩɬɢɜɧɢ ɩɨɞɚɰɢ Ɍɟɫɬ N ɉɪɨɫɟɤ (ɋȾ) Ɇɟɞɢʁɚɧɚ (ɨɩɫɟɝ) ȼɟɥɢɱɢɧɚ ɬɭɦɨɪɚ (cm) 41 5.46 (3.02) 4.3 (2-13) Spearman's rank correlation ρ=0.541; p =0.003 uKIM-1(ng/mgUcr) 41 0.9 (1.84) 0.364 (0.076-9.8) ɂɡ ɬɚɛɟɥɟ ɛɪ. 39. ɫɟ ɜɢɞɢ ɞɚ ɩɨɫɬɨʁɢ ɫɬɚɬɢɫɬɢɱɤɢ ɡɧɚɱɚʁɧɚ ɭɦɟɪɟɧɚ ɞɨ ɞɨɛɪɚ ɤɨɪɟɥɚɰɢʁɚ ɢɡɦɟђɭ ɜɟɥɢɱɢɧɟ ɬɭɦɨɪɚ ɢ ɤɨɪɢɝɨɜɚɧɟ ɤɨɧɰɟɧɬɪɚɰɢʁɟ uKIM-1(ng/mgUcr) (ρ=0.541), ɲɬɨ ɫɟ ɦɨɠɟ ɜɢɞɟɬɢ ɢ ɢɡ ɝɪɚɮɢɤɨɧɚ ɛɪ. 4. Ƚɪɚɮɢɤɨɧ ɛɪ.4. Кɨɪɟɥɚɰɢʁɚ ɜɟɥɢɱɢɧɟ ɬɭɦɨɪɚ ɢ ɤɨɪɢɝɨɜɚɧɟ ɩɪɟɨɩɟɪɚɬɢɜɧɟ ɤɨɧɰɟɧɬɪɚɰɢʁɟ uKIM-1 (ng/mgUcr) Ɉɞ ɢɧɬɟɪɟɫɚ ɡɚ ɢɫɬɪɚɠɢɜɚʃɟ ɛɢɥɨ ʁɟ ɢɫɩɢɬɢɜɚʃɟ ɜɪɟɞɧɨɫɬɢ ɚɩɫɨɥɭɬɧɟ ɤɨɧɰɟɧɬɪɚɰɢʁɟ KIM- 1 ɭ ɭɪɢɧɭ ɩɪɟ ɨɩɟɪɚɰɢʁɟ, ɨɡɧɚɱɟɧɨ ɤɚɨ uKIM-1.0 (ng/ml), ɭ ɨɞɧɨɫɭ ɧɚ ɤɚɬɟɝɨɪɢʁɟ ɜɟɥɢɱɢɧɟ ɬɭɦɨɪɚ. Ⱦɟɫɤɪɢɩɬɢɜɧɢ ɩɨɞɚɰɢ ɢ ɪɟɡɭɥɬɚɬɢ ɬɟɫɬɢɪɚʃɚ ɩɪɢɤɚɡɚɧɢ ɫɭ ɭ ɬɚɛɟɥɢ ɛɪ. 40. y = 0.40922x - 1.33680 0 1 2 3 4 5 6 7 8 9 10 0 2 4 6 8 10 12 14 ȼɟɥɢɱɢɧɚ ɬɭɦɨɪɚ (МЦ) K IM - 1. 0. (n g/ m gU cr ) ɊȿɁɍɅɌȺɌɂ 62 Ɍɚɛɟɥɚ ɛɪ.40. Ⱦɟɫɤɪɢɩɬɢɜɧɢ ɩɨɞɚɰɢ ɤɨɧɰɟɧɬɪɚɰɢʁɟ uKIM-1.0 (nР/ml) ɭ ɨɞɧɨɫɭ ɧɚ ɤɚɬɟɝɨɪɢʁɟ ɜɟɥɢɱɢɧɟ ɬɭɦɨɪɚ ɢ ɪɟɡɭɥɬɚɬɢ ɬɟɫɬɢɪɚʃɚ uKIM-1.0 Ʉɚɬɟɝɨɪɢʁɟ ɜɟɥɢɱɢɧɟ ɬɭɦɨɪɚ Kruskal Wallis-ɨɜ ɬɟɫɬ ≤4МЦ (1) 4.1-7 cm (2) >7 cm (3) N (%) 18 (100%) 11 (100%) 12 (100%) χ22=11 34; p= 0.003 ɉɪɨɫɟɤ (ɋȾ) Ɇɟɞɢʁɚɧɚ (ɨɩɫɟɝ) Ȼɟɡ ɩɨɞɚɬɚɤɚ 0.46 (0.59) 0.29 (0.038-2.106) - 0.52 (0.6) 0.238 (0.075-2) 1 (9.09%) 2.28 (2.13) 1 (0.147-5) - Ʉɚɨ ɲɬɨ ɫɟ ɢɡ ɬɚɛɟɥɟ ɛɪ. 40 ɜɢɞɢ, ɩɨɫɬɨʁɢ ɫɬɚɬɢɫɬɢɱɤɢ ɡɧɚɱɚʁɧɚ ɪɚɡɥɢɤɚ (p=0.003) ɭ ɜɪɟɞɧɨɫɬɢɦɚ uKIM-1.0 ɢɡɦɟђɭ ɤɚɬɟɝɨɪɢʁɚ ɜɟɥɢɱɢɧɟ ɬɭɦɨɪɚ. Ⱦɨɞɚɬɧɢɦ ɬɟɫɬɢɪɚʃɟɦ ɞɨɛɢʁɟɧɢ ɫɭ ɪɟɡɭɥɬɚɬɢ ɩɪɢɤɚɡɚɧɢ ɭ ɬɚɛɟɥɢ ɛɪ. 41. Ɍɚɛɟɥɚ ɛɪ. 41. Ɋɟɡɭɥɬɚɬɢ ɬɟɫɬɢɪɚʃɚ ɜɪɟɞɧɨɫɬɢ uKIM-1.0 (nР/ml) ɩɨ ɩɚɪɨɜɢɦɚ ɤɚɬɟɝɨɪɢʁɚ ɜɟɥɢɱɢɧɟ ɬɭɦɨɪɚ ɉɚɪɨɜɢ ɤɚɬɟɝɨɪɢʁɚ ɜɟɥɢɱɢɧɟ ɬɭɦɨɪɚ Wilcox rank sum test with continuity correction ≤4 cm vs 4.1-7 cm W= 91.5; p*= 0.96 ≤4 cm vs >7 cm W= 32 ; p*= 0.0014 4.1-7 cm vs > 7cm W= 22 ; p*= 0.013 *Bonferroni korekcija: 0.05/3=0.0167 Ʉɚɨ ɲɬɨ ɫɟ ɜɢɞɢ ɢɡ ɬɚɛɟɥɚ ɛɪ. 40. ɢ 41., ɜɪɟɞɧɨɫɬɢ uKIM-1.0 ɭ ɝɪɭɩɢ ɬɭɦɨɪɚ ɜɟʄɢɯ ɨɞ 7 cm ɫɬɚɬɢɫɬɢɱɤɢ ɫɭ ɡɧɚɱɚʁɧɨ ɜɢɲɟ ɭ ɨɞɧɨɫɭ ɧɚ ɜɪɟɞɧɨɫɬɢ uKIM-1.0 ɭ ɝɪɭɩɢ ɬɭɦɨɪɚ ɜɟɥɢɱɢɧɟ 4.1-7 cm ɢɥɢ ɦɚʃɢɯ ɨɞ 4 cm. ȼɪɟɞɧɨɫɬɢ ɚɩɫɨɥɭɬɧɟ ɩɪɟɨɩɟɪɚɬɢɜɧɟ ɤɨɧɰɟɧɬɪɚɰɢʁɟ uKIM-1 ɩɪɟɦɚ ɤɚɬɟɝɨɪɢʁɚɦɚ ɜɟɥɢɱɢɧɟ ɬɭɦɨɪɚ, ɩɪɢɤɚɡɚɧɟ ɫɭ ɧɚ ɝɪɚɮɢɤɨɧɭ ɛɪ.5. ɊȿɁɍɅɌȺɌɂ 63 Ƚɪɚɮɢɤɨɧ ɛɪ.5. ȼɪɟɞɧɨɫɬɢ ɚɩɫɨɥɭɬɧɟ ɤɨɧɰɟɧɬɪɚɰɢʁɟ uKIM-1.0 (ng/ml) ɭ ɨɞɧɨɫɭ ɧɚ ɤɚɬɟɝɨɪɢʁɟ ɜɟɥɢɱɢɧɟ ɬɭɦɨɪɚ ɉɨɪɟɞ ɚɩɫɨɥɭɬɧɢɯ ɢɫɩɢɬɚɧɟ ɫɭ ɢ ɤɨɪɢɝɨɜɚɧɟ ɤɨɧɰɟɧɬɪɚɰɢʁɟ uKIM-1 ɭ ɭɪɢɧɭ ɩɪɟ ɨɩɟɪɚɰɢʁɟ, uKIM-1.0 (ng/mgUcr), ɭ ɨɞɧɨɫɭ ɧɚ ɤɚɬɟɝɨɪɢʁɟ ɜɟɥɢɱɢɧɟ ɬɭɦɨɪɚ. Ⱦɟɫɤɪɢɩɬɢɜɧɢ ɩɨɞɚɰɢ ɢ ɪɟɡɭɥɬɚɬɢ ɬɟɫɬɢɪɚʃɚ ɩɪɢɤɚɡɚɧɢ ɫɭ ɭ ɬɚɛɟɥɢ ɛɪ. 42. Ɍɚɛɟɥɚ ɛɪ. 42. Ⱦɟɫɤɪɢɩɬɢɜɧɢ ɩɨɞɚɰɢ ɤɨɧɰɟɧɬɪɚɰɢʁɟ uKIM-1.0 (ng/mgUcr) ɭ ɨɞɧɨɫɭ ɧɚ ɤɚɬɟɝɨɪɢʁɟ ɜɟɥɢɱɢɧɟ ɬɭɦɨɪɚ ɢ ɪɟɡɭɥɬɚɬɢ ɬɟɫɬɢɪɚʃɚ uKIM-1.0 Ʉɚɬɟɝɨɪɢʁɟ ɜɟɥɢɱɢɧɟ ɬɭɦɨɪɚ Kruskal Wallis- ɨɜɬɟɫɬ ≤4МЦ (1) 4.1-7 cm(2) >7 cm(3) N (%) 18 (100%) 11 (100%) 12 (100%) χ22=13.73; p= 0.001 ɉɪɨɫɟɤ (ЋD) Ɇɟɞɢʁɚɧɚ (ɨɩɫɟɝ) Ȼɟɡ ɩɨɞɚɬɚɤɚ 0.37 (0.32) 0.282 (0.109-1.404) - 0.28 (0.16) 0.23 (0.076-0.565) 1 (9.09%) 2.2 (3.02) 0.662 (0.337-9.8) - Ʉɚɨ ɲɬɨ ɫɟ ɢɡ ɬɚɛɟɥɟ ɛɪ. 42. ɜɢɞɢ, ɩɨɫɬɨʁɢ ɫɬɚɬɢɫɬɢɱɤɢ ɡɧɚɱɚʁɧɚ ɪɚɡɥɢɤɚ (p=0.001) ɭ ɜɪɟɞɧɨɫɬɢɦɚ ɤɨɪɢɝɨɜɚɧɟ ɤɨɧɰɟɧɬɪɚɰɢʁɟ uKIM-1.0 ɢɡɦɟђɭ ɤɚɬɟɝɨɪɢʁɚ ɜɟɥɢɱɢɧɟ ɬɭɦɨɪɚ. Ⱦɨɞɚɬɧɢɦ ɬɟɫɬɢɪɚʃɟɦ ɞɨɛɢʁɟɧɢ ɫɭ ɪɟɡɭɥɬɚɬɢ ɩɪɢɤɚɡɚɧɢ ɭ ɬɚɛɟɥɢ ɛɪ. 43. Ɍɚɛɟɥɚ ɛɪ. 43. Ɋɟɡɭɥɬɚɬɢ ɬɟɫɬɢɪɚʃɚ ɜɪɟɞɧɨɫɬɢ uKIM-1.0 (ng/mgUcr) ɩɨ ɩɚɪɨɜɢɦɚ ɤɚɬɟɝɨɪɢʁɚ ɜɟɥɢɱɢɧɟ ɬɭɦɨɪɚ ɉɚɪɨɜɢ ɤɚɬɟɝɨɪɢʁɚ ɜɟɥɢɱɢɧɟ ɬɭɦɨɪɚ Wilcox rank sum test with continuity correction ≤4 cm vs 4.1-7 cm W= 98; p*= 0.719 ≤4 cm vs >7 cm W= 30 ; p*= 0.001 4.1-7 cm vs > 7cm W= 13 ; p*= 0.001 *Bonferroni ɤɨɪɟɤцɢјɚ: 0.05/3=0.0167 0 0.5 1 1.5 2 2.5 ≤4cŵ 4.1-7 cm >7 cm K IM - 1. 0 (n g/ m l) ɊȿɁɍɅɌȺɌɂ 64 Ʉɚɨ ɲɬɨ ɫɟ ɜɢɞɢ ɢɡ ɬɚɛɟɥɚ ɛɪ. 42. ɢ 43., ɤɨɪɢɝɨɜɚɧɟ ɜɪɟɞɧɨɫɬɢ uKIM-1.0 ɭ ɝɪɭɩɢ ɬɭɦɨɪɚ ɜɟʄɢɯ ɨɞ 7 cm, ɫɬɚɬɢɫɬɢɱɤɢ ɫɭ ɡɧɚɱɚʁɧɨ ɜɢɲɟ ɭ ɨɞɧɨɫɭ ɧɚ ɤɨɪɢɝɨɜɚɧɟ ɜɪɟɞɧɨɫɬɢ uKIM-1.0 ɭ ɝɪɭɩɢ ɬɭɦɨɪɚ ɜɟɥɢɱɢɧɟ 4.1-7cm ɢɥɢ ɦɚʃɢɯ ɨɞ 4 cm. ȼɪɟɞɧɨɫɬɢ ɤɨɪɢɝɨɜɚɧɟ ɩɪɟɨɩɟɪɚɬɢɜɧɟ ɤɨɧɰɟɧɬɪɚɰɢʁɟ uKIM-1 ɩɪɟɦɚ ɤɚɬɟɝɨɪɢʁɚɦɚ ɜɟɥɢɱɢɧɟ ɬɭɦɨɪɚ, ɩɪɢɤɚɡɚɧɟ ɫɭ ɢ ɧɚ ɝɪɚɮɢɤɨɧɭ ɛɪ. 6. Ƚɪɚɮɢɤɨɧ ɛɪ.6. ȼɪɟɞɧɨɫɬɢ ɤɨɪɢɝɨɜɚɧɟ ɤɨɧɰɟɧɬɪɚɰɢʁɟ uKIM-1.0 (ng/mgUcr) ɭ ɨɞɧɨɫɭ ɧɚ ɤɚɬɟɝɨɪɢʁɟ ɜɟɥɢɱɢɧɟ ɬɭɦɨɪɚ ɍ ɢɫɬɪɚɠɢɜɚʃɭ ʁɟ ɫɩɪɨɜɟɞɟɧɨ ɢɫɩɢɬɢɜɚʃɟ ɜɪɟɞɧɨɫɬɢ ɚɩɫɨɥɭɬɧɟ ɤɨɧɰɟɧɬɪɚɰɢʁɟ KIM-1 ɭ ɭɪɢɧɭ ɩɪɟ ɨɩɟɪɚɰɢʁɟ, ɨɡɧɚɱɟɧɨ ɤɚɨ uKIM-1.0 (ng/ml), ɭ ɨɞɧɨɫɭ ɧɚ ɤɚɬɟɝɨɪɢʁɟ ɩɚɬɨɥɨɲɤɢɯ ɫɬɚɞɢʁɭɦɚ ɬɭɦɨɪɚ. Ⱦɟɫɤɪɢɩɬɢɜɧɢ ɩɨɞɚɰɢ ɢ ɪɟɡɭɥɬɚɬɢ ɬɟɫɬɢɪɚʃɚ ɩɪɢɤɚɡɚɧɢ ɫɭ ɭ ɬɚɛɟɥɢ ɛɪ. 44. Ɍɚɛɟɥɚ ɛɪ. 44. Ⱦɟɫɤɪɢɩɬɢɜɧɢ ɩɨɞɚɰɢ ɤɨɧɰɟɧɬɪɚɰɢʁɟ uKIM-1.0 (nР/ml) ɭ ɨɞɧɨɫɭ ɧɚ ɤɚɬɟɝɨɪɢʁɟ ɩɚɬɨɥɨɲɤɢɯ ɫɬɚɞɢʁɭɦɚ ɬɭɦɨɪɚ ɢ ɪɟɡɭɥɬɚɬɢ ɬɟɫɬɢɪɚʃɚ uKIM-1.0 Ʉɚɬɟɝɨɪɢʁɟ ɩɚɬɨɥɨɲɤɢɯ ɫɬɚɞɢʁɭɦɚ ɬɭɦɨɪɚ Kruskal Wallis-ɨɜ ɬɟɫɬ pɌ1К (1) pɌ1Л (2) pT2a (3) pT3a (4) N (%) 13(100%) 10 (100%) 3 (100%) 14 (100%) ɉɪɨɫɟɤ (ɋȾ) 0.26 (0.14) 0.43 (0.59) 0.44 (0.38) 2.27 (1.94) χ 2 2=13.73; p= 0.0004 Ɇɟɞɢʁɚɧɚ (ɨɩɫɟɝ) 0.27 (0.038-0.459) 0.23 (0.075-2) 0.31 (0.14-0.873) 1.5 (0.212-5) Ȼɟɡ ɩɨɞɚɬɚɤɚ - 1 (9.09%) - - Ʉɚɨ ɲɬɨ ɫɟ ɢɡ ɬɚɛɟɥɟ ɛɪ. 44. ɜɢɞɢ, ɩɨɫɬɨʁɢ ɫɬɚɬɢɫɬɢɱɤɢ ɡɧɚɱɚʁɧɚ ɪɚɡɥɢɤɚ (p=0.0004) ɭ ɜɪɟɞɧɨɫɬɢɦɚ ɚɩɫɨɥɭɬɧɟ ɤɨɧɰɟɧɬɪɚɰɢʁɟ uKIM-1.0 ɢɡɦɟђɭ ɤɚɬɟɝɨɪɢʁɚ ɩɚɬɨɥɨɲɤɢɯ ɫɬɚɞɢʁɭɦɚ ɬɭɦɨɪɚ. 0 0.5 1 1.5 2 2.5 ≤4cm 4.1-7 cm >7 cm K IM -ϭ. Ϭ к о̬ ̛̐. ;Ŷg /ŵ gU crͿ ɊȿɁɍɅɌȺɌɂ 65 Ⱦɨɞɚɬɧɢɦ ɬɟɫɬɢɪɚʃɟɦ ɞɨɛɢʁɟɧɢ ɫɭ ɪɟɡɭɥɬɚɬɢ ɩɪɢɤɚɡɚɧɢ ɭ ɬɚɛɟɥɢ ɛɪ. 45. Ɍɚɛɟɥɚ ɛɪ. 45. Ɋɟɡɭɥɬɚɬɢ ɬɟɫɬɢɪɚʃɚ ɜɪɟɞɧɨɫɬɢ uKIM-1.0 (nР/ml) ɩɨ ɩɚɪɨɜɢɦɚ ɤɚɬɟɝɨɪɢʁɚ ɩɚɬɨɥɨɲɤɢɯ ɫɬɚɞɢʁɭɦɚ ɬɭɦɨɪɚ ɉɚɪɨɜɢ ɤɚɬɟɝɨɪɢʁɚ ɩɚɬɨɥɨɲɤɢɯ ɫɬɚɞɢʁɭɦɚ ɬɭɦɨɪɚ Wilcox rank sum test with continuity correction pT1ɚ vs pT1ɛ W= 70; p*= 0.784 pT1ɚ vs pT2ɚ W= 15 ; p*= 0.611 pT1ɚ vs pT3ɚ W= 12 ; p*= 0.0001 pT1ɛ vs pT2ɚ W= 10 ; p*= 0.468 pT1ɛ vs pT3ɚ W= 15.5; p*= 0.0015 pT2ɚ vs pT3ɚ W= 5; p*= 0.0488 *BonПОrronТ ɤɨɪɟɤцɢјɚ: 0.05/6=0.0083 Ʉɚɨ ɲɬɨ ɫɟ ɜɢɞɢ ɢɡ ɬɚɛɟɥɚ ɛɪ. 44. ɢ 45., ɩɪɟɨɩɟɪɚɬɢɜɧɟ ɜɪɟɞɧɨɫɬɢ uKIM-1 ɭ ɝɪɭɩɢ ɬɭɦɨɪɚ ɩɚɬɨɥɨɲɤɨɝ ɫɬɚɞɢʁɭɦɚ pT3ɚ, ɫɬɚɬɢɫɬɢɱɤɢ ɫɭ ɡɧɚɱɚʁɧɨ ɜɢɲɟ ɭ ɨɞɧɨɫɭ ɧɚ ɩɪɟɨɩɟɪɚɬɢɜɧɟ ɜɪɟɞɧɨɫɬɢ uKIM-1 ɭ ɝɪɭɩɢ ɬɭɦɨɪɚ ɫɬɚɞɢʁɭɦɚ pT1ɚ ɢ pT1ɛ. ɉɨɪɟɞ ɚɩɫɨɥɭɬɧɢɯ ɢɫɩɢɬɚɧɟ ɫɭ ɢ ɤɨɪɢɝɨɜɚɧɟ ɤɨɧɰɟɧɬɪɚɰɢʁɟ KIM-1 ɭ ɭɪɢɧɭ ɩɪɟ ɨɩɟɪɚɰɢʁɟ, uKIM-1.0 (ng/mgUcr) ɭ ɨɞɧɨɫɭ ɧɚ ɤɚɬɟɝɨɪɢʁɟ ɩɚɬɨɥɨɲɤɨɝ ɫɬɚɞɢʁɭɦɚ ɬɭɦɨɪɚ, ɚ ɞɟɫɤɪɢɩɬɢɜɧɢ ɩɨɞɚɰɢ ɢ ɪɟɡɭɥɬɚɬɢ ɬɟɫɬɢɪɚʃɚ ɩɪɢɤɚɡɚɧɢ ɫɭ ɭ ɬɚɛɟɥɢ ɛɪ. 46. Ɍɚɛɟɥɚ ɛɪ. 46. Ⱦɟɫɤɪɢɩɬɢɜɧɢ ɩɨɞɚɰɢ ɤɨɧɰɟɧɬɪɚɰɢʁɟ uKIM-1.0 (ng/mgUcr) ɭ ɨɞɧɨɫɭ ɧɚ ɤɚɬɟɝɨɪɢʁɟ ɩɚɬɨɥɨɲɤɢɯ ɫɬɚɞɢʁɭɦɚ ɬɭɦɨɪɚ ɢ ɪɟɡɭɥɬɚɬɢ ɬɟɫɬɢɪɚʃɚ uKIM-1.0 Ʉɚɬɟɝɨɪɢʁɟ ɩɚɬɨɥɨɲɤɢɯ ɫɬɚɞɢʁɭɦɚ ɬɭɦɨɪɚ Kruskal Wallis-ɨɜ ɬɟɫɬ pT1a (1) pT1b (2) pT2a (3) pT3a (4) N (%) 13(100%) 10 (100%) 3 (100%) 14 (100%) ɉɪɨɫɟɤ (ɋȾ) 0.27 (0.11) 0.25 (0.15) 0.38 (0.08) 2.07 (2.8) χ22=22.38; p= 5.42*10-5 Ɇɟɞɢʁɚɧɚ (ɨɩɫɟɝ) 0.25 (0.109-0.401) 0.21 (0.07-0.56) 0.34(0.34-0.47) 0.8 (0.26-9.8) Ȼɟɡ ɩɨɞɚɬɚɤɚ - 1 (9.09%) - - Ʉɚɨ ɲɬɨ ɫɟ ɢɡ ɬɚɛɟɥɟ ɛɪ. 46. ɜɢɞɢ, ɩɨɫɬɨʁɢ ɫɬɚɬɢɫɬɢɱɤɢ ɡɧɚɱɚʁɧɚ ɪɚɡɥɢɤɚ (p=5.42*10-5) ɭ ɩɪɟɨɩɟɪɚɬɢɜɧɢɦ ɜɪɟɞɧɨɫɬɢɦɚ ɤɨɪɢɝɨɜɚɧɢɯ ɤɨɧɰɟɧɬɪɚɰɢʁɚ uKIM-1 ɢɡɦɟђɭ ɤɚɬɟɝɨɪɢʁɚ ɩɚɬɨɥɨɲɤɢɯ ɫɬɚɞɢʁɭɦɚ ɬɭɦɨɪɚ. Ⱦɨɞɚɬɧɢɦ ɬɟɫɬɢɪɚʃɟɦ ɞɨɛɢʁɟɧɢ ɫɭ ɪɟɡɭɥɬɚɬɢ ɩɪɢɤɚɡɚɧɢ ɭ ɬɚɛɟɥɢ ɛɪ. 47. Ɍɚɛɟɥɚ ɛɪ. 47. Ɋɟɡɭɥɬɚɬɢ ɬɟɫɬɢɪɚʃɚ ɜɪɟɞɧɨɫɬɢ uKIM-1.0 (ng/mgUcr) ɩɨ ɩɚɪɨɜɢɦɚ ɤɚɬɟɝɨɪɢʁɚ ɩɚɬɨɥɨɲɤɢɯ ɫɬɚɞɢʁɭɦɚ ɬɭɦɨɪɚ ɉɚɪɨɜɢ ɤɚɬɟɝɨɪɢʁɚ ɩɚɬɨɥɨɲɤɢɯ ɫɬɚɞɢʁɭɦɚ ɬɭɦɨɪɚ Wilcox rank sum test with continuity correction pT1ɚ vs pT1ɛ W= 73.5; p*= 0.6197 pT1ɚ vs pT2ɚ W= 10 ; p*= 0.2393 pT 1ɚ vs pT3ɚ W= 6 ; p*= 2.99*10-6 pT1ɛ vs pT2ɚ W= 5 ; p*= 0.1119 ɊȿɁɍɅɌȺɌɂ 66 pT1ɛ vs pT3ɚ W=9; p*=9.89*10-5 pT2ɚ vs pT3ɚ W= 6; p*= 0.0676 *BonПОrronТ ɤɨɪɟɤцɢјɚ: 0.05/6=0.0083 Ʉɚɨ ɲɬɨ ɫɟ ɜɢɞɢ ɢɡ ɬɚɛɟɥɚ ɛɪ. 46. ɢ 47., ɞɨɛɢʁɟɧɟ ɩɪɟɨɩɟɪɚɬɢɜɧɟ ɤɨɪɢɝɨɜɚɧɟ ɜɪɟɞɧɨɫɬɢ uKIM-1 ɭ ɝɪɭɩɢ ɬɭɦɨɪɚ ɩɚɬɨɥɨɲɤɨɝ ɫɬɚɞɢʁɭɦɚ pT3ɚ, ɫɬɚɬɢɫɬɢɱɤɢ ɫɭ ɡɧɚɱɚʁɧɨ ɜɢɲɟ ɭ ɨɞɧɨɫɭ ɧɚ ɩɪɟɨɩɟɪɚɬɢɜɧɟ ɜɪɟɞɧɨɫɬɢ uKIM-1 ɭ ɝɪɭɩɢ ɬɭɦɨɪɚ ɫɬɚɞɢʁɭɦɚ pT1ɚ ɢ pT1ɛ. Ɉɞ ɢɧɬɟɪɟɫɚ ɡɚ ɢɫɬɪɚɠɢɜɚʃɟ ɛɢɥɨ ʁɟ ɢɫɩɢɬɢɜɚʃɟ ɜɪɟɞɧɨɫɬɢ ɚɩɫɨɥɭɬɧɟ ɤɨɧɰɟɧɬɪɚɰɢʁɟ KIM- 1 ɭ ɭɪɢɧɭ ɩɪɟ ɨɩɟɪɚɰɢʁɟ, ɨɡɧɚɱɟɧɨ ɤɚɨ uKIM-1.0 (ng/ml), ɭ ɨɞɧɨɫɭ ɧɚ ɤɚɬɟɝɨɪɢʁɟ ɯɢɫɬɨɥɨɲɤɨɝ ɝɪɚɞɭɫɚ ɬɭɦɨɪɚ. Ⱦɟɫɤɪɢɩɬɢɜɧɢ ɩɨɞɚɰɢ ɢ ɪɟɡɭɥɬɚɬɢ ɬɟɫɬɢɪɚʃɚ ɩɪɢɤɚɡɚɧɢ ɫɭ ɭ ɬɚɛɟɥɢ ɛɪ. 48. Ɍɚɛɟɥɚ ɛɪ. 48. Ⱦɟɫɤɪɢɩɬɢɜɧɢ ɩɨɞɚɰɢ ɤɨɧɰɟɧɬɪɚɰɢʁɟ uKIM-1.0 (nР/ml) ɭ ɨɞɧɨɫɭ ɧɚ ɤɚɬɟɝɨɪɢʁɟ ɯɢɫɬɨɥɨɲɤɨɝ ɝɪɚɞɭɫɚ ɬɭɦɨɪɚ ɢ ɪɟɡɭɥɬɚɬɢ ɬɟɫɬɢɪɚʃɚ uKIM-1.0 Ʉɚɬɟɝɨɪɢʁɟ ɯɢɫɬɨɥɨɲɤɨɝ ɝɪɚɞɭɫɚ ɬɭɦɨɪɚ Kruskal Wallis-ɨɜ ɬɟɫɬ G2 (1) G3 (2) G4 (3) N (%) 31 (100%) 8 (100%) 1 (100%) χ22=11.70; p= 0.003 ɉɪɨɫɟɤ (ɋȾ) Ɇɟɞɢʁɚɧɚ (ɨɩɫɟɝ) Ȼɟɡ ɩɨɞɚɬɚɤɚ 0.61 (0.99) 0.273 (0.038-5) 1 (3.12%) 2.35 (2.21) 1 (0.368-5) - 3 (-) 3 (3-3) - Ʉɚɨ ɲɬɨ ɫɟ ɢɡ ɬɚɛɟɥɟ ɛɪ. 48. ɜɢɞɢ, ɩɨɫɬɨʁɢ ɫɬɚɬɢɫɬɢɱɤɢ ɡɧɚɱɚʁɧɚ ɪɚɡɥɢɤɚ (p=0.003) ɭ ɩɪɟɨɩɟɪɚɬɢɜɧɢɦ ɜɪɟɞɧɨɫɬɢɦɚ uKIM-1.0 ɢɡɦɟђɭ ɤɚɬɟɝɨɪɢʁɚ ɯɢɫɬɨɥɨɲɤɨɝ ɝɪɚɞɭɫɚ ɬɭɦɨɪɚ. Ⱦɨɞɚɬɧɢɦ ɬɟɫɬɢɪɚʃɟɦ ɞɨɛɢʁɟɧɢ ɫɭ ɪɟɡɭɥɬɚɬɢ ɩɪɢɤɚɡɚɧɢ ɭ ɬɚɛɟɥɢ ɛɪ. 49. Ɍɚɛɟɥɚ ɛɪ. 49. Ɋɟɡɭɥɬɚɬɢ ɬɟɫɬɢɪɚʃɚ ɜɪɟɞɧɨɫɬɢ uKIM-1.0 (nР/ml) ɩɨ ɩɚɪɨɜɢɦɚ ɤɚɬɟɝɨɪɢʁɚ ɯɢɫɬɨɥɨɲɤɨɝ ɝɪɚɞɭɫɚ ɬɭɦɨɪɚ ɉɚɪɨɜɢ ɤɚɬɟɝɨɪɢʁɚ ɯɢɫɬɨɥɨɲɤɨɝ ɝɪɚɞɭɫɚ ɬɭɦɨɪɚ Wilcox rank sum test with continuity correction G2vs G3 W= 33.5; p*= 0.0017 G2 vs G4 W= 1 ; p*= 0.1294 G3 vs G4 W= 3 ; p*= 0.8432 *Bonferroni korekcija: 0.05/3=0.0167 Ʉɚɨ ɲɬɨ ɫɟ ɜɢɞɢ ɢɡ ɬɚɛɟɥɚ ɛɪ. 48. ɢ 49., ɩɪɟɨɩɟɪɚɬɢɜɧɟ ɜɪɟɞɧɨɫɬɢ uKIM-1 ɭ ɝɪɭɩɢ ɬɭɦɨɪɚ ɯɢɫɬɨɥɨɲɤɨɝ ɝɪɚɞɭɫɚ G3 ɫɬɚɬɢɫɬɢɱɤɢ ɫɭ ɡɧɚɱɚʁɧɨ ɜɢɲɟ (p*= 0.0017) ɭ ɨɞɧɨɫɭ ɧɚ ɜɪɟɞɧɨɫɬɢ uKIM-1 ɭ ɝɪɭɩɢ ɬɭɦɨɪɚ ɝɪɚɞɭɫɚ G2. ȼɪɟɞɧɨɫɬ uKIM-1 ɤɨɞ ɩɚɰɢʁɟɧɬɚ ɫɚ ɬɭɦɨɪɨɦ ɯɢɫɬɨɥɨɲɤɨɝ ɝɪɚɞɭɫɚ G4 ʁɟ ɜɢɲɚ ɭ ɨɞɧɨɫɭ ɧɚ ɜɪɟɞɧɨɫɬ uKIM-1ɭ ɝɪɭɩɢ ɬɭɦɨɪɚ ɝɪɚɞɭɫɚ G2 ɢ G3, ɚɥɢ ɛɟɡ ɫɬɚɬɢɫɬɢɱɤɟ ɡɧɚɱɚʁɧɨɫɬɢ. ɍ ɢɫɬɪɚɠɢɜɚʃɭ ɫɭ ɢɫɩɢɬɚɧɟ ɢ ɩɪɟɨɩɟɪɚɬɢɜɧɟ ɤɨɪɢɝɨɜɚɧɟ ɤɨɧɰɟɧɬɪɚɰɢʁɟ uKIM-1, uKIM- 1.0(ng/mgUcr), ɭ ɨɞɧɨɫɭ ɧɚ ɤɚɬɟɝɨɪɢʁɟɯɢɫɬɨɥɨɲɤɨɝ ɝɪɚɞɭɫɚ ɬɭɦɨɪɚ. Ⱦɟɫɤɪɢɩɬɢɜɧɢ ɩɨɞɚɰɢ ɢ ɪɟɡɭɥɬɚɬɢ ɬɟɫɬɢɪɚʃɚ ɩɪɢɤɚɡɚɧɢ ɫɭ ɭ ɬɚɛɟɥɢ ɛɪ. 50. ɊȿɁɍɅɌȺɌɂ 67 Ɍɚɛɟɥɚ ɛɪ. 50. Ⱦɟɫɤɪɢɩɬɢɜɧɢ ɩɨɞɚɰɢ ɤɨɧɰɟɧɬɪɚɰɢʁɟ uKIM-1.0 (ng/mgUcr) ɭ ɨɞɧɨɫɭ ɧɚ ɤɚɬɟɝɨɪɢʁɟ ɯɢɫɬɨɥɨɲɤɨɝ ɝɪɚɞɭɫɚ ɬɭɦɨɪɚ ɢ ɪɟɡɭɥɬɚɬɢ ɬɟɫɬɢɪɚʃɚ uKIM-1.0 Ʉɚɬɟɝɨɪɢʁɟ ɯɢɫɬɨɥɨɲɤɨɝ ɝɪɚɞɭɫɚ ɬɭɦɨɪɚ Kruskal Wallis-ɨɜ ɬɟɫɬ G2 (1) G3 (2) G4 (3) N (%) 31 (100%) 8 (100%) 1 (100%) χ22=12.40; p= 0.002 ɉɪɨɫɟɤ (ɋȾ) Ɇɟɞɢʁɚɧɚ (ɨɩɫɟɝ) Ȼɟɡ ɩɨɞɚɬɚɤɚ 0.42 (0.53) 0.257 (0.076-2.92) 1 (3.12%) 2.74 (3.57) 0.783 (0.342-9.8) - 1.16 (-) 1.16 (1.16-1.16) - Ʉɚɨ ɲɬɨ ɫɟ ɢɡ ɬɚɛɟɥɟ ɛɪ. 50. ɜɢɞɢ, ɩɨɫɬɨʁɢ ɫɬɚɬɢɫɬɢɱɤɢ ɡɧɚɱɚʁɧɚ ɪɚɡɥɢɤɚ (p=0.002) ɭ ɩɪɟɨɩɟɪɚɬɢɜɧɢɦ ɤɨɪɢɝɨɜɚɧɢɦ ɜɪɟɞɧɨɫɬɢɦɚ uKIM-1.0 ɢɡɦɟђɭ ɤɚɬɟɝɨɪɢʁɚ ɯɢɫɬɨɥɨɲɤɨɝ ɝɪɚɞɭɫɚ ɬɭɦɨɪɚ. Ⱦɨɞɚɬɧɢɦ ɬɟɫɬɢɪɚʃɟɦ ɞɨɛɢʁɟɧɢ ɫɭ ɪɟɡɭɥɬɚɬɢ ɩɪɢɤɚɡɚɧɢ ɭ ɬɚɛɟɥɢ ɛɪ. 51. Ɍɚɛɟɥɚ ɛɪ. 51. Ɋɟɡɭɥɬɚɬɢ ɬɟɫɬɢɪɚʃɚ ɜɪɟɞɧɨɫɬɢ uKIM-1.0 (ng/mgUcr) ɩɨ ɩɚɪɨɜɢɦɚ ɤɚɬɟɝɨɪɢʁɚ ɯɢɫɬɨɥɨɲɤɨɝ ɝɪɚɞɭɫɚ ɬɭɦɨɪɚ ɉɚɪɨɜɢ ɤɚɬɟɝɨɪɢʁɚ ɯɢɫɬɨɥɨɲɤɨɝ ɝɪɚɞɭɫɚ ɬɭɦɨɪɚ Wilcox rank sum test with continuity correction G2vs G3 W= 29; p*= 0.001 G2 vs G4 W= 2 ; p*= 0.1591 G3 vs G4 W= 3 ; p*= 0.8889 *Bonferroni korekcija: 0.05/3=0.0167 Ʉɚɨ ɲɬɨ ɫɟ ɜɢɞɢ ɢɡ ɬɚɛɟɥɚ ɛɪ. 50 ɢ 51., ɩɪɟɨɩɟɪɚɬɢɜɧɟ ɤɨɪɢɝɨɜɚɧɟ ɜɪɟɞɧɨɫɬɢ uKIM-1 ɭ ɝɪɭɩɢ ɬɭɦɨɪɚ ɯɢɫɬɨɥɨɲɤɨɝ ɝɪɚɞɭɫɚ G3 ɫɬɚɬɢɫɬɢɱɤɢ ɫɭ ɡɧɚɱɚʁɧɨ ɜɢɲɟ (p*= 0.001) ɭ ɨɞɧɨɫɭ ɧɚ ɜɪɟɞɧɨɫɬɢ uKIM-1 ɭ ɝɪɭɩɢ ɬɭɦɨɪɚ ɝɪɚɞɭɫɚ G2. Ʉɨɪɢɝɨɜɚɧɚ ɜɪɟɞɧɨɫɬ uKIM-1 ɤɨɞ ɩɚɰɢʁɟɧɬɚ ɫɚ ɬɭɦɨɪɨɦ ɯɢɫɬɨɥɨɲɤɨɝ ɝɪɚɞɭɫɚ G4 ʁɟ ɧɢɠɚ ɭ ɨɞɧɨɫɭ ɧɚ ɜɪɟɞɧɨɫɬ uKIM-1 ɭ ɝɪɭɩɢ ɬɭɦɨɪɚ ɝɪɚɞɭɫɚ G3, ɚɥɢ ɛɟɡ ɫɬɚɬɢɫɬɢɱɤɟ ɡɧɚɱɚʁɧɨɫɬɢ. Ɉɞ ɢɧɬɟɪɟɫɚ ɡɚ ɢɫɬɪɚɠɢɜɚʃɟ ɛɢɥɨ ʁɟ ɢɫɩɢɬɢɜɚʃɟ ɜɪɟɞɧɨɫɬɢ ɚɩɫɨɥɭɬɧɟ ɤɨɧɰɟɧɬɪɚɰɢʁɟ KIM- 1 ɭ ɭɪɢɧɭ ɩɪɟ ɨɩɟɪɚɰɢʁɟ, ɨɡɧɚɱɟɧɨ ɤɚɨ uKIM-1.0(ng/ml), ɭ ɨɞɧɨɫɭ ɧɚ ɤɚɬɟɝɨɪɢʁɟ ɥɢɦɮɧɨ- ɜɚɫɤɭɥɚɪɧɟ ɢɧɜɚɡɢʁɟ. Ⱦɟɫɤɪɢɩɬɢɜɧɢ ɩɨɞɚɰɢ ɢ ɪɟɡɭɥɬɚɬɢ ɬɟɫɬɢɪɚʃɚ ɩɪɢɤɚɡɚɧɢ ɫɭ ɭ ɬɚɛɟɥɢ ɛɪ. 52. Ɍɚɛɟɥɚ ɛɪ. 52. Ⱦɟɫɤɪɢɩɬɢɜɧɢ ɩɨɞɚɰɢ ɤɨɧɰɟɧɬɪɚɰɢʁɟ uKIM-1.0 (nР/ml) ɭ ɨɞɧɨɫɭ ɧɚ ɤɚɬɟɝɨɪɢʁɟ ɥɢɦɮɧɨɜɚɫɤɭɥɚɪɧɟ ɢɧɜɚɡɢʁɟ ɢ ɪɟɡɭɥɬɚɬɢ ɬɟɫɬɢɪɚʃɚ uKIM-1.0 Ʉɚɬɟɝɨɪɢʁɟ ɥɢɦɮɧɨ-ɜɚɫɤɭɥɚɪɧɟ ɢɧɜɚɡɢʁɟ Kruskal Wallis-ɨɜ ɬɟɫɬ L0V0 (1) L0V1 (L1V0) (2) L1V1 (3) N (%) 7 (100%) 13 (100%) 20 (100%) χ22=9.59; p= 0.008 ɉɪɨɫɟɤ (ɋȾ) Ɇɟɞɢʁɚɧɚ (ɨɩɫɟɝ) Ȼɟɡ ɩɨɞɚɬɚɤɚ 0.25 (0.16) 0.256 (0.038-0.459) - 0.39 (0.5) 0.247 (0.102-2) - 1.7 (1.85) 0.936 (0.075-5) 1 (4.76%) ɊȿɁɍɅɌȺɌɂ 68 Ʉɚɨ ɲɬɨ ɫɟ ɢɡ ɬɚɛɟɥɟ ɛɪ. 52. ɜɢɞɢ, ɩɨɫɬɨʁɢ ɫɬɚɬɢɫɬɢɱɤɢ ɡɧɚɱɚʁɧɚ ɪɚɡɥɢɤɚ (p=0.008) ɭ ɩɪɟɨɩɟɪɚɬɢɜɧɢɦ ɜɪɟɞɧɨɫɬɢɦɚ uKIM-1.0 ɢɡɦɟђɭ ɤɚɬɟɝɨɪɢʁɚɥɢɦɮɧɨ-ɜɚɫɤɭɥɚɪɧɟ ɢɧɜɚɡɢʁɟ. Ⱦɨɞɚɬɧɢɦ ɬɟɫɬɢɪɚʃɟɦ ɞɨɛɢʁɟɧɢ ɫɭ ɪɟɡɭɥɬɚɬɢ ɩɪɢɤɚɡɚɧɢ ɭ ɬɚɛɟɥɢ ɛɪ. 53. Ɍɚɛɟɥɚ ɛɪ. 53. Ɋɟɡɭɥɬɚɬɢ ɬɟɫɬɢɪɚʃɚ ɜɪɟɞɧɨɫɬɢ uKIM-1.0 (nР/ml) ɩɨ ɩɚɪɨɜɢɦɚ ɤɚɬɟɝɨɪɢʁɚ ɥɢɦɮɧɨ-ɜɚɫɤɭɥɚɪɧɟ ɢɧɜɚɡɢʁɟ ɉɚɪɨɜɢ ɤɚɬɟɝɨɪɢʁɚ ɥɢɦɮɧɨ-ɜɚɫɤɭɥɚɪɧɟ ɢɧɜɚɡɢʁɟ Wilcox rank sum test with continuity correction L0V0 vs L0V1 (L1V0) W= 40; p*= 0.6992 L0V0 vs L1V1 W= 26 ; p*= 0.0159 L0V1 (L1V0) vs L1V1 W= 60.5; p*= 0.0109 *Bonferroni korekcija: 0.05/3=0.0167 Ʉɚɨ ɲɬɨ ɫɟ ɜɢɞɢ ɢɡ ɬɚɛɟɥɚ ɛɪ. 52. ɢ 53., ɚɩɫɨɥɭɬɧɟ ɩɪɟɨɩɟɪɚɬɢɜɧɟ ɜɪɟɞɧɨɫɬɢ uKIM-1 ɭ ɝɪɭɩɢ ɫɚ ɥɢɦɮɧɨ-ɜɚɫɤɭɥɚɪɧɨɦ ɢɧɜɚɡɢʁɨɦ (ɤɚɬɟɝɨɪɢʁɚ L1V1) ɫɬɚɬɢɫɬɢɱɤɢ ɫɭ ɡɧɚɱɚʁɧɨ ɜɢɲɟ ɭ ɨɞɧɨɫɭ ɧɚ ɝɪɭɩɭ ɛɟɡ ɥɢɦɮɧɨɜɚɫɤɭɥɚɪɧɟ ɢɧɜɚɡɢʁɟ (ɤɚɬɟɝɨɪɢʁɚ L0V0) ɢ ɧɚ ɝɪɭɩɭ ɫɚ ɬɭɦɨɪɫɤɨɦ ɥɢɦɮɧɨɦ ɢɥɢ ɜɚɫɤɭɥɚɪɧɨɦ ɢɧɜɚɡɢʁɨɦ (ɤɚɬɟɝɨɪɢʁɚ L0V1, ɨɞɧɨɫɧɨ L1V0). Ɋɟɡɭɥɬɚɬɢ ɬɟɫɬɢɪɚʃɚ ɤɨɪɢɝɨɜɚɧɟ ɤɨɧɰɟɧɬɪɚɰɢʁɟ uKIM-1, uKIM-1.0 (ng/mgUcr), ɭ ɨɞɧɨɫɭ ɧɚ ɤɚɬɟɝɨɪɢʁɟ ɬɭɦɨɪɫɤɟ ɥɢɦɮɧɨɜɚɫɤɭɥɚɪɧɟ ɢɧɜɚɡɢʁɟ ɩɪɢɤɚɡɚɧɢ ɫɭ ɭ ɬɚɛɟɥɢ ɛɪ. 54. Ɍɚɛɟɥɚ ɛɪ.54. Ⱦɟɫɤɪɢɩɬɢɜɧɢ ɩɨɞɚɰɢ ɤɨɧɰɟɧɬɪɚɰɢʁɟ uKIM-1.0 (ng/mgUcr) ɭ ɨɞɧɨɫɭ ɧɚ ɤɚɬɟɝɨɪɢʁɟɥɢɦɮɧɨ-ɜɚɫɤɭɥɚɪɧɟ ɢɧɜɚɡɢʁɟ ɢ ɪɟɡɭɥɬɚɬɢ ɬɟɫɬɢɪɚʃɚ uKIM-1.0 Ʉɚɬɟɝɨɪɢʁɟ ɥɢɦɮɧɨɜɚɫɤɭɥɚɪɧɟ ɢɧɜɚɡɢʁɟ Kruskal Wallis-ɨɜ ɬɟɫɬ L0V0 (1) L0V1 (L1V0) (2) L1V1 (3) N (%) 7 (100%) 13 (100%) 20 (100%) χ22=16.99; p= 0.0002 ɉɪɨɫɟɤ (ɋȾ) Ɇɟɞɢʁɚɧɚ (ɨɩɫɟɝ) Ȼɟɡ ɩɨɞɚɬɚɤɚ 0.18 (0.05) 0.154 (0.141-0.247) - 0.3 (0.13) 0.318 (0.109-0.565) - 1.54 (2.46) 0.482 (0.076-9.8) 1 (4.76%) Ʉɚɨ ɲɬɨ ɫɟ ɢɡ ɬɚɛɟɥɟ ɛɪ. 54. ɜɢɞɢ, ɩɨɫɬɨʁɢ ɫɬɚɬɢɫɬɢɱɤɢ ɡɧɚɱɚʁɧɚ ɪɚɡɥɢɤɚ (p=0.0002) ɭ ɤɨɪɢɝɨɜɚɧɢɦ ɩɪɟɨɩɟɪɚɬɢɜɧɢɦ ɜɪɟɞɧɨɫɬɢɦɚ uKIM-1.0 ɢɡɦɟђɭ ɤɚɬɟɝɨɪɢʁɚ ɥɢɦɮɧɨ- ɜɚɫɤɭɥɚɪɧɟ ɢɧɜɚɡɢʁɟ. Ⱦɨɞɚɬɧɢɦ ɬɟɫɬɢɪɚʃɟɦ ɞɨɛɢʁɟɧɢ ɫɭ ɪɟɡɭɥɬɚɬɢ ɩɪɢɤɚɡɚɧɢ ɭ ɬɚɛɟɥɢ ɛɪ. 55. Ɍɚɛɟɥɚ ɛɪ. 55. Ɋɟɡɭɥɬɚɬɢ ɬɟɫɬɢɪɚʃɚ ɜɪɟɞɧɨɫɬɢ uKIM-1.0 (ng/mgUcr) ɩɨ ɩɚɪɨɜɢɦɚ ɤɚɬɟɝɨɪɢʁɚɥɢɦɮɧɨ-ɜɚɫɤɭɥɚɪɧɟ ɢɧɜɚɡɢʁɟ ɉɚɪɨɜɢ ɤɚɬɟɝɨɪɢʁɚ ɥɢɦɮɧɨ-ɜɚɫɤɭɥɚɪɧɟ ɢɧɜɚɡɢʁɟ Wilcox rank sum test with continuity correction L0V0 vs L0V1 (L1V0) W= 23.5; p*= 0.0883 L0V0 vs L1V1 W= 8; p*= 0.0001 L0V1 (L1V0) vs L1V1 W= 48; p*= 0.0019 *Bonferroni korekcija: 0.05/3=0.0167 ɊȿɁɍɅɌȺɌɂ 69 Ʉɚɨ ɲɬɨ ɫɟ ɜɢɞɢ ɢɡ ɬɚɛɟɥɚ 54. ɢ 55., ɤɨɪɢɝɨɜɚɧɟ ɩɪɟɨɩɟɪɚɬɢɜɧɟ ɜɪɟɞɧɨɫɬɢ uKIM-1 ɭ ɝɪɭɩɢ ɫɚ ɥɢɦɮɧɨ-ɜɚɫɤɭɥɚɪɧɨɦ ɢɧɜɚɡɢʁɨɦ (ɤɚɬɟɝɨɪɢʁɚ L1V1) ɫɬɚɬɢɫɬɢɱɤɢ ɫɭ ɡɧɚɱɚʁɧɨ ɜɢɲɟ ɭ ɨɞɧɨɫɭ ɧɚ ɝɪɭɩɭ ɛɟɡ ɥɢɦɮɧɨ-ɜɚɫɤɭɥɚɪɧɟ ɢɧɜɚɡɢʁɟ (ɤɚɬɟɝɨɪɢʁɚ L0V0) ɢ ɧɚ ɝɪɭɩɭ ɫɚ ɬɭɦɨɪɫɤɨɦ ɥɢɦɮɧɨɦ ɢɥɢ ɜɚɫɤɭɥɚɪɧɨɦ ɢɧɜɚɡɢʁɨɦ (ɤɚɬɟɝɨɪɢʁɚ L0V1 ɨɞɧɨɫɧɨ L1V0). ɍ ɢɫɬɪɚɠɢɜɚʃɭ ʁɟ ɫɩɪɨɜɟɞɟɧɨ ɢɫɩɢɬɢɜɚʃɟ ɜɪɟɞɧɨɫɬɢ ɚɩɫɨɥɭɬɧɟ ɤɨɧɰɟɧɬɪɚɰɢʁɟ KIM-1 ɭ ɭɪɢɧɭ ɩɪɟ ɨɩɟɪɚɰɢʁɟ, ɨɡɧɚɱɟɧɨ ɤɚɨ uKIM-1.0 (ng/ml), ɭ ɨɞɧɨɫɭ ɧɚ ɤɚɬɟɝɨɪɢʁɟ ɩɨɫɬɨɩɟɪɚɬɢɜɧɨɝ TNM ɫɬɚɞɢʁɭɦɚ. Ⱦɟɫɤɪɢɩɬɢɜɧɢ ɩɨɞɚɰɢ ɢ ɪɟɡɭɥɬɚɬɢ ɬɟɫɬɢɪɚʃɚ ɩɪɢɤɚɡɚɧɢ ɫɭ ɭ ɬɚɛɟɥɢ ɛɪ. 56. Ɍɚɛɟɥɚ ɛɪ. 56. Ⱦɟɫɤɪɢɩɬɢɜɧɢ ɩɨɞɚɰɢ ɤɨɧɰɟɧɬɪɚɰɢʁɟ uKIM-1.0 (nР/ml) ɭ ɨɞɧɨɫɭ ɧɚ ɤɚɬɟɝɨɪɢʁɟ ɩɨɫɬɨɩɟɪɚɬɢɜɧɨɝ TNM ɫɬɚɞɢʁɭɦɚ ɢ ɪɟɡɭɥɬɚɬɢ ɬɟɫɬɢɪɚʃɚ uKIM-1.0 Ʉɚɬɟɝɨɪɢʁɟ ɩɨɫɬɨɩɟɪɚɬɢɜɧɨɝ TNM ɫɬɚɞɢʁɭɦɚ Kruskal Wallis-ɨɜ ɬɟɫɬ I (1) II (2) III (3) IV(4) N (%) 22 (100%) 3 (100%) 13 (100%) 2 (100%) ɉɪɨɫɟɤ (ɋȾ) 0.34 (0.41) 0.44 (0.38) 2.03 (1.88) 2.76 (3.16) χ 2 2=13.84; p= 0.002 Ɇɟɞɢʁɚɧɚ (ɨɩɫɟɝ) 0.25 (0.038-2) 0.31 (0.147-0.873) 1 (0.144-5) 2.76 (0.529-5) Ȼɟɡ ɩɨɞɚɬɚɤɚ 1 (4.35%) - - - Ʉɚɨ ɲɬɨ ɫɟ ɢɡ ɬɚɛɟɥɟ ɛɪ. 56. ɜɢɞɢ, ɩɨɫɬɨʁɢ ɫɬɚɬɢɫɬɢɱɤɢ ɡɧɚɱɚʁɧɚ ɪɚɡɥɢɤɚ (p=0.002) ɭ ɜɪɟɞɧɨɫɬɢɦɚ ɤɨɧɰɟɧɬɪɚɰɢʁɟ uKIM-1.0 ɢɡɦɟђɭ ɤɚɬɟɝɨɪɢʁɚ ɩɨɫɬɨɩɟɪɚɬɢɜɧɨɝ TNM ɫɬɚɞɢʁɭɦɚ. Ⱦɨɞɚɬɧɢɦ ɬɟɫɬɢɪɚʃɟɦ ɞɨɛɢʁɟɧɢ ɫɭ ɪɟɡɭɥɬɚɬɢ ɩɪɢɤɚɡɚɧɢ ɭ ɬɚɛɟɥɢ ɛɪ. 57. Ɍɚɛɟɥɚ ɛɪ. 57. Ɋɟɡɭɥɬɚɬɢ ɬɟɫɬɢɪɚʃɚ ɜɪɟɞɧɨɫɬɢ uKIM-1.0 (nР/ml) ɩɨ ɩɚɪɨɜɢɦɚ ɤɚɬɟɝɨɪɢʁɚ ɩɨɫɬɨɩɟɪɚɬɢɜɧɨɝ TNM ɫɬɚɞɢʁɭɦɚ ɉɚɪɨɜɢ ɤɚɬɟɝɨɪɢʁɚ ɩɚɬɨɥɨɲɤɢɯ ɫɬɚɞɢʁɭɦɚ ɬɭɦɨɪɚ Wilcox rank sum test with continuity correction I vs II W= 25; p*= 0.5504 I vs III W= 41.5; p*= 0.0006 I vs IV W= 2; p*= 0.0289 II vs III W= 7; p*= 0.1044 II vs IV W=1; p*=0.4 III vs IV W= 11.5; p*= 0.8634 *BonПОrronТ ɤɨɪɟɤцɢјɚ: 0.05/6=0.0083 Ʉɚɨ ɲɬɨ ɫɟ ɜɢɞɢ ɢɡ ɬɚɛɟɥɚ ɛɪ. 56.ɢ 57., ɞɨɛɢʁɟɧɟ ɩɪɟɨɩɟɪɚɬɢɜɧɟ ɚɩɫɨɥɭɬɧɟ ɜɪɟɞɧɨɫɬɢ uKIM-1ɭ ɝɪɭɩɢ ɩɚɰɢʁɟɧɚɬɚ ɫɚ ɬɪɟʄɢɦ ɩɨɫɬɨɩɟɪɚɬɢɜɧɢɦ TNM ɫɬɚɞɢʁɭɦɨɦ, ɫɬɚɬɢɫɬɢɱɤɢ ɫɭ ɡɧɚɱɚʁɧɨ ɜɢɲɟ ɭ ɨɞɧɨɫɭ ɧɚ ɩɪɟɨɩɟɪɚɬɢɜɧɟ ɜɪɟɞɧɨɫɬɢ uKIM-1 ɭ ɝɪɭɩɢ ɩɚɰɢʁɟɧɚɬɚ ɤɨʁɢ ɫɭ ɛɢɥɢ ɭ ɩɪɜɨɦ TNM ɫɬɚɞɢʁɭɦɭ. ɊȿɁɍɅɌȺɌɂ 70 ɂɫɬɢ ɨɛɥɢɤ ɬɟɫɬɢɪɚʃɚ ɫɩɪɨɜɟɞɟɧ ʁɟ ɢ ɫɚ ɤɨɪɢɝɨɜɚɧɨɦ ɤɨɧɰɟɧɬɪɚɰɢʁɨɦ uKIM-1, uKIM-1.0 (ng/mgUcr), ɭ ɨɞɧɨɫɭ ɧɚ ɤɚɬɟɝɨɪɢʁɟ ɩɨɫɬɨɩɟɪɚɬɢɜɧɨɝ TNM ɫɬɚɞɢʁɭɦɚ, ɚ ɞɟɫɤɪɢɩɬɢɜɧɢ ɩɨɞɚɰɢ ɢ ɪɟɡɭɥɬɚɬɢ ɬɟɫɬɢɪɚʃɚ ɩɪɢɤɚɡɚɧɢ ɫɭ ɭ ɬɚɛɟɥɢ ɛɪ. 58. Ɍɚɛɟɥɚ ɛɪ. 58. Ⱦɟɫɤɪɢɩɬɢɜɧɢ ɩɨɞɚɰɢ ɤɨɧɰɟɧɬɪɚɰɢʁɟ uKIM-1.0 (ng/mgUcr) ɭ ɨɞɧɨɫɭ ɧɚ ɤɚɬɟɝɨɪɢʁɟɩɨɫɬɨɩɟɪɚɬɢɜɧɨɝ TNM ɫɬɚɞɢʁɭɦɚ ɢ ɪɟɡɭɥɬɚɬɢ ɬɟɫɬɢɪɚʃɚ uKIM-1.0 Ʉɚɬɟɝɨɪɢʁɟ ɩɨɫɬɨɩɟɪɚɬɢɜɧɨɝ TNM ɫɬɚɞɢʁɭɦɚ Kruskal Wallis-ɨɜ ɬɟɫɬ I (1) II (2) III (3) IV(4) N (%) 22 (100%) 3 (100%) 12 (100%) 2 (100%) ɉɪɨɫɟɤ (ɋȾ) 0.26 (0.13) 0.38 (0.08) 1.45 (1.78) 5.15 (6.58) χ 2 2=20.15; p= 0.0001 Ɇɟɞɢʁɚɧɚ (ɨɩɫɟɝ) 0.22 (0.076-0.565) 0.34 (0.337-0.47) 0.77 (0.24-6.67) 5.15 (0.494-9.8) Ȼɟɡ ɩɨɞɚɬɚɤɚ 1 (4.35%) - 1 (7.69%) - Ʉɚɨ ɲɬɨ ɫɟ ɢɡ ɬɚɛɟɥɟ ɛɪ. 58. ɜɢɞɢ, ɩɨɫɬɨʁɢ ɫɬɚɬɢɫɬɢɱɤɢ ɡɧɚɱɚʁɧɚ ɪɚɡɥɢɤɚ (p=0.0001) ɭ ɜɪɟɞɧɨɫɬɢɦɚ ɩɪɟɨɩɟɪɚɬɢɜɧɢɯ ɤɨɪɢɝɨɜɚɧɢɯ ɤɨɧɰɟɧɬɪɚɰɢʁɚ uKIM-1 ɢɡɦɟђɭ ɤɚɬɟɝɨɪɢʁɚ ɩɨɫɬɨɩɟɪɚɬɢɜɧɨɝ TNM ɫɬɚɞɢʁɭɦɚ. Ⱦɨɞɚɬɧɢɦ ɬɟɫɬɢɪɚʃɟɦ ɞɨɛɢʁɟɧɢ ɫɭ ɪɟɡɭɥɬɚɬɢ ɩɪɢɤɚɡɚɧɢ ɭ ɬɚɛɟɥɢ ɛɪ. 59. Ɍɚɛɟɥɚ ɛɪ. 59. Ɋɟɡɭɥɬɚɬɢ ɬɟɫɬɢɪɚʃɚ ɜɪɟɞɧɨɫɬɢ uKIM-1.0 (ng/mgUcr) ɩɨ ɩɚɪɨɜɢɦɚ ɤɚɬɟɝɨɪɢʁɚ ɩɨɫɬɨɩɟɪɚɬɢɜɧɨɝ TNM ɫɬɚɞɢʁɭɦɚ ɉɚɪɨɜɢ ɤɚɬɟɝɨɪɢʁɚ ɩɚɬɨɥɨɲɤɢɯ ɫɬɚɞɢʁɭɦɚ ɬɭɦɨɪɚ Wilcox rank sum test with continuity correction I vs II W= 15; p*= 0.1433 I vs III W= 24; p*= 5.21*10-5 I vs IV W= 4; p*= 0.0322 II vs III W= 9; p*= 0.1893 II vs IV W=4; p*=0.2 III vs IV W= 8; p*= 0.4762 *BonПОrronТ ɤɨɪɟɤцɢјɚ: 0.05/6=0.0083 Ʉɚɨ ɲɬɨ ɫɟ ɜɢɞɢ ɢɡ ɬɚɛɟɥɚ ɛɪ. 58.ɢ 59., ɞɨɛɢʁɟɧɟ ɩɪɟɨɩɟɪɚɬɢɜɧɟ ɤɨɪɢɝɨɜɚɧɟ ɜɪɟɞɧɨɫɬɢ uKIM-1ɭ ɝɪɭɩɢ ɩɚɰɢʁɟɧɚɬɚ ɫɚ ɬɪɟʄɢɦ ɩɨɫɬɨɩɟɪɚɬɢɜɧɢɦ TNM ɫɬɚɞɢʁɭɦɨɦ, ɫɬɚɬɢɫɬɢɱɤɢ ɫɭ ɡɧɚɱɚʁɧɨ ɜɢɲɟ ɭ ɨɞɧɨɫɭ ɧɚ ɩɪɟɨɩɟɪɚɬɢɜɧɟ ɜɪɟɞɧɨɫɬɢ uKIM-1 ɭ ɝɪɭɩɢ ɩɚɰɢʁɟɧɚɬɚ ɤɨʁɢ ɫɭ ɛɢɥɢ ɭ ɩɪɜɨɦ TNM ɫɬɚɞɢʁɭɦɭ. 4.4.2. ɂɫɩɢɬɢɜɚʃɟ ɩɨɜɟɡɚɧɨɫɬɢ ɩɪɟɨɩɟɪɚɬɢɜɧɢɯ ɜɪɟɞɧɨɫɬɢ uAQP-1 ɢ ɩɚɬɨɯɢɫɬɨɥɨɲɤɢɯ ɤɚɪɚɤɬɟɪɢɫɬɢɤɚ ɬɭɦɨɪɚ ɍ ɬɚɛɟɥɢ ɛɪ. 60. ɧɚɜɟɞɟɧɢ ɫɭ ɞɟɫɤɪɢɩɬɢɜɧɢ ɩɨɞɚɰɢ ɢ ɪɟɡɭɥɬɚɬɢ ɬɟɫɬɢɪɚʃɚ ɜɪɟɞɧɨɫɬɢ ɜɟɥɢɱɢɧɟ ɬɭɦɨɪɚ (cm) ɢ ɜɪɟɞɧɨɫɬɢ ɚɩɫɨɥɭɬɧɟ ɤɨɧɰɟɧɬɪɚɰɢʁɟ uAQP-1 (ng/ml) ɭ ɝɪɭɩɢ ɨɛɨɥɟɥɢɯ. ɊȿɁɍɅɌȺɌɂ 71 Tɚɛɟɥɚ ɛɪ. 60. Ⱦɟɫɤɪɢɩɬɢɜɧɢ ɩɨɞɚɰɢ ɢ ɪɟɡɭɥɬɚɬɢ ɬɟɫɬɢɪɚʃɚ ɜɪɟɞɧɨɫɬɢ ɜɟɥɢɱɢɧɟ ɬɭɦɨɪɚ (cm) ɢ uAQP-1(ng/ml) ɉɚɪɚɦɟɬɪɢ Ⱦɟɫɤɪɢɩɬɢɜɧɢ ɩɨɞɚɰɢ Ɍɟɫɬ N ɉɪɨɫɟɤ (ɋȾ) Ɇɟɞɢʁɚɧɚ (ɨɩɫɟɝ) ȼɟɥɢɱɢɧɚ ɬɭɦɨɪɚ (cm) 39 5.5 (3.05) 4.4 (2-13) Spearman's rank correlation ρ=0.123; p =0.454 uAQP-1 (ng/ml) 39 0.1 (0.04) 0.086 (0-0.287) ɂɡ ɬɚɛɟɥɟ ɛɪ. 60.ɫɟ ɜɢɞɢ ɞɚ ɧɟ ɩɨɫɬɨʁɢ ɫɬɚɬɢɫɬɢɱɤɢ ɡɧɚɱɚʁɧɚ ɤɨɪɟɥɚɰɢʁɚ ɢɡɦɟђɭ ɜɟɥɢɱɢɧɟ ɬɭɦɨɪɚ ɢ ɚɩɫɨɥɭɬɧɟ ɤɨɧɰɟɧɬɪɚɰɢʁɟ uAQP-1(ng/ml), ɲɬɨ ɫɟ ɦɨɠɟ ɜɢɞɟɬɢ ɢ ɢɡ ɝɪɚɮɢɤɨɧɚ ɛɪ. 7. Ƚɪɚɮɢɤɨɧ ɛɪ. 7. Кɨɪɟɥɚɰɢʁɚ ɢɡɦɟђɭ ɜɟɥɢɱɢɧɟ ɬɭɦɨɪɚ ɢ ɚɩɫɨɥɭɬɧɟ ɩɪɟɨɩɟɪɚɬɢɜɧɟ ɤɨɧɰɟɧɬɪɚɰɢʁɟ uAQP-1 (ng/ml) ɍ ɬɚɛɟɥɢ ɛɪ. 61. ɧɚɜɟɞɟɧɢ ɫɭ ɞɟɫɤɪɢɩɬɢɜɧɢ ɩɨɞɚɰɢ ɢ ɪɟɡɭɥɬɚɬɢ ɬɟɫɬɢɪɚʃɚ ɜɪɟɞɧɨɫɬɢ ɜɟɥɢɱɢɧɟ ɬɭɦɨɪɚ (cm) ɢ ɜɪɟɞɧɨɫɬɢ ɤɨɪɢɝɨɜɚɧɟ ɤɨɧɰɟɧɬɪɚɰɢʁɟ uAQP-1(ng/mgUcr) ɭ ɝɪɭɩɢ ɨɛɨɥɟɥɢɯ. y = 0.00094x + 0.09091 0.0 0.1 0.2 0.3 0 2 4 6 8 10 12 14 ȼɟɥɢɱɢɧɚ ɬɭɦɨɪɚ (МЦ) A QP 1. 0 (n g/ m l) ɊȿɁɍɅɌȺɌɂ 72 Tɚɛɟɥɚ ɛɪ. 61. Ⱦɟɫɤɪɢɩɬɢɜɧɢ ɩɨɞɚɰɢ ɢ ɪɟɡɭɥɬɚɬɢ ɬɟɫɬɢɪɚʃɚ ɜɪɟɞɧɨɫɬɢ ɜɟɥɢɱɢɧɟ ɬɭɦɨɪɚ (cm) ɢ uAQP-1(ng/mgUcr) ɉɚɪɚɦɟɬɪɢ Ⱦɟɫɤɪɢɩɬɢɜɧɢ ɩɨɞɚɰɢ Ɍɟɫɬ N ɉɪɨɫɟɤ (ɋȾ) Ɇɟɞɢʁɚɧɚ (ɨɩɫɟɝ) ȼɟɥɢɱɢɧɚ ɬɭɦɨɪɚ (cm) 39 5.5 (3.05) 4.4 (2-13) Spearman's rank correlation ρ=–0.124; p =0.453 uAQP-1 (ng/mgUcr) 39 0.11 (0.09) 0.079 (0-0.412) ɂɡ ɬɚɛɟɥɟ ɛɪ. 61.ɫɟ ɜɢɞɢ ɞɚ ɧɟ ɩɨɫɬɨʁɢ ɫɬɚɬɢɫɬɢɱɤɢ ɡɧɚɱɚʁɧɚ ɤɨɪɟɥɚɰɢʁɚ ɢɡɦɟђɭ ɜɟɥɢɱɢɧɟ ɬɭɦɨɪɚ ɢ ɜɪɟɞɧɨɫɬɢ ɤɨɪɢɝɨɜɚɧɟ ɤɨɧɰɟɧɬɪɚɰɢʁɟ uAQP-1(ng/mgUcr), ɲɬɨ ʁɟ ɩɪɢɤɚɡɚɧɨ ɧɚ ɝɪɚɮɢɤɨɧɭ ɛɪ. 8. Ƚɪɚɮɢɤɨɧ ɛɪ. 8. Кɨɪɟɥɚɰɢʁɚ ɢɡɦɟђɭ ɜɟɥɢɱɢɧɟ ɬɭɦɨɪɚ ɢ ɤɨɪɢɝɨɜɚɧɟ ɩɪɟɨɩɟɪɚɬɢɜɧɟ ɤɨɧɰɟɧɬɪɚɰɢʁɟ uAQP-1 (ng/mgUcr) Ɉɞ ɢɧɬɟɪɟɫɚ ɡɚ ɢɫɬɪɚɠɢɜɚʃɟ ɛɢɥɨ ʁɟ ɢɫɩɢɬɢɜɚʃɟ ɜɪɟɞɧɨɫɬɢ ɚɩɫɨɥɭɬɧɟ ɤɨɧɰɟɧɬɪɚɰɢʁɟ AQP-1 ɭ ɭɪɢɧɭ ɩɪɟ ɨɩɟɪɚɰɢʁɟ, ɨɡɧɚɱɟɧɨ ɤɚɨ uAQP-1.0 (ng/ml), ɭ ɨɞɧɨɫɭ ɧɚ ɤɚɬɟɝɨɪɢʁɟ ɜɟɥɢɱɢɧɟ ɬɭɦɨɪɚ. Ⱦɟɫɤɪɢɩɬɢɜɧɢ ɩɨɞɚɰɢ ɢ ɪɟɡɭɥɬɚɬɢ ɬɟɫɬɢɪɚʃɚ ɩɪɢɤɚɡɚɧɢ ɫɭ ɭ ɬɚɛɟɥɢ ɛɪ. 62. y = -0.00322x + 0.12570 0.0 0.1 0.2 0.3 0.4 0.5 0 2 4 6 8 10 12 14 ȼɟɥɢɱɢɧɚ ɬɭɦɨɪɚ (МЦ) AЉ Ј1 .0. ɤɨ ɪɢ ɝ. ( n g /m g U cr ) ɊȿɁɍɅɌȺɌɂ 73 Ɍɚɛɟɥɚ ɛɪ. 62. Ⱦɟɫɤɪɢɩɬɢɜɧɢ ɩɨɞɚɰɢ ɤɨɧɰɟɧɬɪɚɰɢʁɟ uAQP-1.0 (nР/ml) ɭ ɨɞɧɨɫɭ ɧɚ ɤɚɬɟɝɨɪɢʁɟ ɜɟɥɢɱɢɧɟ ɬɭɦɨɪɚ ɢ ɪɟɡɭɥɬɚɬɢ ɬɟɫɬɢɪɚʃɚ uAQP-1.0 Ʉɚɬɟɝɨɪɢʁɟ ɜɟɥɢɱɢɧɟ ɬɭɦɨɪɚ Kruskal Wallis-ɨɜ ɬɟɫɬ ≤4cm (1) 4.1-7 cm (2) >7 cm (3) N (%) 17 (100%) 10 (100%) 12 (100%) χ22=1.025; p= 0.599 ɉɪɨɫɟɤ (ɋȾ) Ɇɟɞɢʁɚɧɚ (ɨɩɫɟɝ) Ȼɟɡ ɩɨɞɚɬɚɤɚ 0.1 (0.06) 0.085 (0.073-0.287) 1(5.56%) 0.08 (0.03) 0.087 (0-0.097) 1 (9.09%) 0.1 (0.04) 0,087 (0.077-0.207) - Ʉɚɨ ɲɬɨ ɫɟ ɢɡ ɬɚɛɟɥɟ ɛɪ. 62. ɜɢɞɢ, ɧɟ ɩɨɫɬɨʁɢ ɫɬɚɬɢɫɬɢɱɤɢ ɡɧɚɱɚʁɧɚ ɪɚɡɥɢɤɚ ɭ ɜɪɟɞɧɨɫɬɢɦɚ uAQP-1.0 ɢɡɦɟђɭ ɤɚɬɟɝɨɪɢʁɚ ɜɟɥɢɱɢɧɟ ɬɭɦɨɪɚ. Ⱦɨɞɚɬɧɢɦ ɬɟɫɬɢɪɚʃɟɦ ɞɨɛɢʁɟɧɢ ɫɭ ɪɟɡɭɥɬɚɬɢ ɩɪɢɤɚɡɚɧɢ ɭ ɬɚɛɟɥɢ ɛɪ. 63. Ɍɚɛɟɥɚ ɛɪ. 63. Ɋɟɡɭɥɬɚɬɢ ɬɟɫɬɢɪɚʃɚ ɜɪɟɞɧɨɫɬɢ uAQP-1.0 (nР/ml) ɩɨ ɩɚɪɨɜɢɦɚ ɤɚɬɟɝɨɪɢʁɚ ɜɟɥɢɱɢɧɟ ɬɭɦɨɪɚ ɉɚɪɨɜɢ ɤɚɬɟɝɨɪɢʁɚ ɜɟɥɢɱɢɧɟ ɬɭɦɨɪɚ Wilcox rank sum test with continuity correction ≤4 cm vs 4.1-7 cm W= 95.5; p*= 0.615 ≤4 cm vs >7 cm W= 85; p*= 0.464 4.1-7 cm vs > 7cm W= 47; p*= 0.408 *Bonferroni korekcija: 0.05/3=0.0167 Ʉɚɨ ɲɬɨ ɫɟ ɜɢɞɢ ɢɡ ɬɚɛɟɥɟ ɛɪ. 63., ɬɟɫɬɢɪɚʃɟɦ ɜɪɟɞɧɨɫɬɢ uAQP-1.0 (ng/ml) ɩɨ ɩɚɪɨɜɢɦɚ ɤɚɬɟɝɨɪɢʁɚ ɜɟɥɢɱɢɧɟ ɬɭɦɨɪɚ ɧɢʁɟ ɞɨɛɢʁɟɧɚ ɫɬɚɬɢɫɬɢɱɤɢ ɡɧɚɱɚʁɧɚ ɪɚɡɥɢɤɚ ɢɡɦɟђɭ ɩɚɪɨɜɚ. ɉɨɪɟɞ ɚɩɫɨɥɭɬɧɢɯ ɢɫɩɢɬɚɧɟ ɫɭ ɢ ɤɨɪɢɝɨɜɚɧɟ ɤɨɧɰɟɧɬɪɚɰɢʁɟ uAQP-1ɭ ɭɪɢɧɭ ɩɪɟ ɨɩɟɪɚɰɢʁɟ, uAQP-1.0(ng/mgUcr), ɭ ɨɞɧɨɫɭ ɧɚ ɤɚɬɟɝɨɪɢʁɟ ɜɟɥɢɱɢɧɟ ɬɭɦɨɪɚ. Ⱦɟɫɤɪɢɩɬɢɜɧɢ ɩɨɞɚɰɢ ɢ ɪɟɡɭɥɬɚɬɢ ɬɟɫɬɢɪɚʃɚ ɩɪɢɤɚɡɚɧɢ ɫɭ ɭ ɬɚɛɟɥɢ ɛɪ. 64. Ɍɚɛɟɥɚ ɛɪ. 64. Ⱦɟɫɤɪɢɩɬɢɜɧɢ ɩɨɞɚɰɢ ɤɨɧɰɟɧɬɪɚɰɢʁɟ uAQP-1.0 (ng/mgUcr) ɭ ɨɞɧɨɫɭ ɧɚ ɤɚɬɟɝɨɪɢʁɟ ɜɟɥɢɱɢɧɟ ɬɭɦɨɪɚ ɢ ɪɟɡɭɥɬɚɬɢ ɬɟɫɬɢɪɚʃɚ uAQP-1.0 Ʉɚɬɟɝɨɪɢʁɟ ɜɟɥɢɱɢɧɟ ɬɭɦɨɪɚ Kruskal Wallis-ɨɜ ɬɟɫɬ ≤4cm (1) 4.1-7 cm (2) >7 cm (3) N (%) 17 (100%) 10 (100%) 12 (100%) χ22=2.790; p= 0.248 ɉɪɨɫɟɤ (ɋȾ) Ɇɟɞɢʁɚɧɚ (ɨɩɫɟɝ) Ȼɟɡ ɩɨɞɚɬɚɤɚ 0.14 (0.12) 0.093 (0.023-0.412) 1(5.56%) 0.07 (0.04) 0.062 (0-0.144) 1 (9.09%) 0.1 (0.07) 0.077 (0.037-0.248) - Ʉɚɨ ɲɬɨ ɫɟ ɢɡ ɬɚɛɟɥɟ ɛɪ. 64. ɜɢɞɢ, ɧɟ ɩɨɫɬɨʁɢ ɫɬɚɬɢɫɬɢɱɤɢ ɡɧɚɱɚʁɧɚ ɪɚɡɥɢɤɚ ɭ ɜɪɟɞɧɨɫɬɢɦɚ ɤɨɪɢɝɨɜɚɧɟ ɤɨɧɰɟɧɬɪɚɰɢʁɟ uAQP-1.0 ɢɡɦɟђɭ ɤɚɬɟɝɨɪɢʁɚ ɜɟɥɢɱɢɧɟ ɬɭɦɨɪɚ. Ⱦɨɞɚɬɧɢɦ ɬɟɫɬɢɪɚʃɟɦ ɞɨɛɢʁɟɧɢ ɫɭ ɪɟɡɭɥɬɚɬɢ ɩɪɢɤɚɡɚɧɢ ɭ ɬɚɛɟɥɢ ɛɪ. 65. ɊȿɁɍɅɌȺɌɂ 74 Ɍɚɛɟɥɚ ɛɪ. 65. Ɋɟɡɭɥɬɚɬɢ ɬɟɫɬɢɪɚʃɚ ɜɪɟɞɧɨɫɬɢ uAQP-1.0 (ng/mgUcr) ɩɨ ɩɚɪɨɜɢɦɚ ɤɚɬɟɝɨɪɢʁɚ ɜɟɥɢɱɢɧɟ ɬɭɦɨɪɚ ɉɚɪɨɜɢ ɤɚɬɟɝɨɪɢʁɚ ɜɟɥɢɱɢɧɟ ɬɭɦɨɪɚ Wilcox rank sum test with continuity correction ≤4 cm vs 4.1-7 cm W= 118; p*= 0.492 ≤4 cm vs >7 cm W= 118; p*= 0.493 4.1-7 cm vs > 7cm W= 46; p*= 0.373 *Bonferroni korekcija: 0.05/3=0.0167 Ʉɚɨ ɲɬɨ ɫɟ ɜɢɞɢ ɢɡ ɬɚɛɟɥɟ ɛɪ. 65., ɬɟɫɬɢɪɚʃɟɦ ɜɪɟɞɧɨɫɬɢ ɤɨɪɢɝɨɜɚɧɢɯ ɤɨɧɰɟɧɬɪɚɰɢʁɚ uAQP-1.0 (ng/mgUcr) ɩɨ ɩɚɪɨɜɢɦɚ ɤɚɬɟɝɨɪɢʁɚ ɜɟɥɢɱɢɧɟ ɬɭɦɨɪɚ ɧɢʁɟ ɞɨɛɢʁɟɧɚ ɫɬɚɬɢɫɬɢɱɤɢ ɡɧɚɱɚʁɧɚ ɪɚɡɥɢɤɚ ɢɡɦɟђɭ ɩɚɪɨɜɚ. ɍ ɢɫɬɪɚɠɢɜɚʃɭ ʁɟ ɫɩɪɨɜɟɞɟɧɨ ɢɫɩɢɬɢɜɚʃɟ ɜɪɟɞɧɨɫɬɢ ɚɩɫɨɥɭɬɧɟ ɤɨɧɰɟɧɬɪɚɰɢʁɟAQP-1 ɭ ɭɪɢɧɭ ɩɪɟ ɨɩɟɪɚɰɢʁɟ, ɨɡɧɚɱɟɧɨ ɤɚɨ uAQP-1.0 (ng/ml), ɭ ɨɞɧɨɫɭ ɧɚ ɤɚɬɟɝɨɪɢʁɟ ɩɚɬɨɥɨɲɤɢɯ ɫɬɚɞɢʁɭɦɚ ɬɭɦɨɪɚ. Ⱦɟɫɤɪɢɩɬɢɜɧɢ ɩɨɞɚɰɢ ɢ ɪɟɡɭɥɬɚɬɢ ɬɟɫɬɢɪɚʃɚ ɩɪɢɤɚɡɚɧɢ ɫɭ ɭ ɬɚɛɟɥɢ ɛɪ. 66. Ɍɚɛɟɥɚ ɛɪ. 66. Ⱦɟɫɤɪɢɩɬɢɜɧɢ ɩɨɞɚɰɢ ɤɨɧɰɟɧɬɪɚɰɢʁɟ AQP-1.0 (nР/ml) ɭ ɨɞɧɨɫɭ ɧɚ ɤɚɬɟɝɨɪɢʁɟ ɩɚɬɨɥɨɲɤɢɯ ɫɬɚɞɢʁɭɦɚ ɬɭɦɨɪɚ ɢ ɪɟɡɭɥɬɚɬɢ ɬɟɫɬɢɪɚʃɚ uAQP-1.0 Ʉɚɬɟɝɨɪɢʁɟ ɩɚɬɨɥɨɲɤɢɯ ɫɬɚɞɢʁɭɦɚ ɬɭɦɨɪɚ Kruskal Wallis-ɨɜ ɬɟɫɬ 1a (1) 1b (2) 2a (3) 3a (4) N (%) 13(100%) 10 (90.91%) 3 (100%) 13 (100%) ɉɪɨɫɟɤ (ɋȾ) 0.09 (0.03) 0.08 (0.03) 0.09 (0.01) 0.11 (0.06) χ 2 2=1.315; p= 0.725 Ɇɟɞɢʁɚɧɚ (ɨɩɫɟɝ) 0.082 (0.073-0.2) 0.087 (0-0.097) 0.092 (0.077-0.094) 0.086 (0.075-0.287) Ȼɟɡ ɩɨɞɚɬɚɤɚ - 1 (9.09%) - 1 (7.14%) Ʉɚɨ ɲɬɨ ɫɟ ɢɡ ɬɚɛɟɥɟ ɛɪ. 66. ɜɢɞɢ, ɧɟ ɩɨɫɬɨʁɢ ɫɬɚɬɢɫɬɢɱɤɢ ɡɧɚɱɚʁɧɚ ɪɚɡɥɢɤɚ ɭ ɜɪɟɞɧɨɫɬɢɦɚ ɤɨɧɰɟɧɬɪɚɰɢʁɟuAQP-1.0 ɢɡɦɟђɭ ɤɚɬɟɝɨɪɢʁɚ ɩɚɬɨɥɨɲɤɢɯ ɫɬɚɞɢʁɭɦɚ ɬɭɦɨɪɚ. Ⱦɨɞɚɬɧɢɦ ɬɟɫɬɢɪɚʃɟɦ ɞɨɛɢʁɟɧɢ ɫɭ ɪɟɡɭɥɬɚɬɢ ɩɪɢɤɚɡɚɧɢ ɭ ɬɚɛɟɥɢ ɛɪ. 67. Ɍɚɛɟɥɚ ɛɪ. 67. Ɋɟɡɭɥɬɚɬɢ ɬɟɫɬɢɪɚʃɚ ɜɪɟɞɧɨɫɬɢuAQP-1.0(nР/ml) ɩɨ ɩɚɪɨɜɢɦɚ ɤɚɬɟɝɨɪɢʁɚ ɩɚɬɨɥɨɲɤɢɯ ɫɬɚɞɢʁɭɦɚ ɬɭɦɨɪɚ ɉɚɪɨɜɢ ɤɚɬɟɝɨɪɢʁɚ ɩɚɬɨɥɨɲɤɢɯ ɫɬɚɞɢʁɭɦɚ ɬɭɦɨɪɚ Wilcox rank sum test with continuity correction 1ɚ vs 1ɛ W= 66.5; p*= 0.950 1ɚ vs 2ɚ W= 19; p*= 1 1ɚ vs 3ɚ W= 60; p*= 0.218 1ɛ vs 2ɚ W= 11.5; p*= 0.611 1ɛ vs 3ɚ W= 54; p*= 0.513 2ɚ vs 3ɚ W=19.5; p*=1 *BonПОrronТ ɤɨɪɟɤцɢјɚ: 0.05/6=0.0083 ɊȿɁɍɅɌȺɌɂ 75 Ʉɚɨ ɲɬɨ ɫɟ ɜɢɞɢ ɢɡ ɬɚɛɟɥɟ ɛɪ. 67., ɬɟɫɬɢɪɚʃɟɦ ɜɪɟɞɧɨɫɬɢ uAQP-1.0 (ng/ml) ɩɨ ɩɚɪɨɜɢɦɚ ɤɚɬɟɝɨɪɢʁɚ ɩɚɬɨɥɨɲɤɢɯ ɫɬɚɞɢʁɭɦɚɬɭɦɨɪɚ ɧɢʁɟ ɞɨɛɢʁɟɧɚ ɫɬɚɬɢɫɬɢɱɤɢ ɡɧɚɱɚʁɧɚ ɪɚɡɥɢɤɚ ɢɡɦɟђɭ ɩɚɪɨɜɚ. ɍ ɬɚɛɟɥɢ ɛɪ. 68. ɩɪɢɤɚɡɚɧɟ ɫɭ ɤɨɪɢɝɨɜɚɧɟ ɤɨɧɰɟɧɬɪɚɰɢʁɟ uAQP-1 ɭ ɭɪɢɧɭ ɩɪɟ ɨɩɟɪɚɰɢʁɟ, uAQP-1.0 (ng/mgUcr) ɭ ɨɞɧɨɫɭ ɧɚ ɤɚɬɟɝɨɪɢʁɟ ɩɚɬɨɥɨɲɤɢɯ ɫɬɚɞɢʁɭɦɚ ɬɭɦɨɪɚ. Ɍɚɛɟɥɚ ɛɪ. 68. Ⱦɟɫɤɪɢɩɬɢɜɧɢ ɩɨɞɚɰɢ ɤɨɧɰɟɧɬɪɚɰɢʁɟ AQP-1.0 (ng/mgUcr) ɭ ɨɞɧɨɫɭ ɧɚ ɤɚɬɟɝɨɪɢʁɟ ɩɚɬɨɥɨɲɤɢɯ ɫɬɚɞɢʁɭɦɚ ɬɭɦɨɪɚ ɢ ɪɟɡɭɥɬɚɬɢ ɬɟɫɬɢɪɚʃɚ uAQP-1.0 Ʉɚɬɟɝɨɪɢʁɟ ɩɚɬɨɥɨɲɤɢɯ ɫɬɚɞɢʁɭɦɚ ɬɭɦɨɪɚ Kruskal Wallis-ɨɜ ɬɟɫɬ 1a (1) 1b (2) 2a (3) 3a (4) N (%) 13(100%) 10 (90.91%) 3 (100%) 13 (100%) ɉɪɨɫɟɤ (ɋȾ) 0.14 (0.13) 0.08 (0.07) 0.13 (0.11) 0.1 (0.06) χ 2 2=1.472; p= 0.689 Ɇɟɞɢʁɚɧɚ (ɨɩɫɟɝ) 0.079 (0.023-0.412) 0.062 (0-0.243) 0.101 (0.037-0.248) 0.08 (0.037-0.239) Ȼɟɡ ɩɨɞɚɬɚɤɚ - 1 (9.09%) - 1(7.14%) Ʉɚɨ ɲɬɨ ɫɟ ɢɡ ɬɚɛɟɥɟ ɛɪ. 68. ɜɢɞɢ, ɧɟ ɩɨɫɬɨʁɢ ɫɬɚɬɢɫɬɢɱɤɢ ɡɧɚɱɚʁɧɚ ɪɚɡɥɢɤɚ ɭ ɜɪɟɞɧɨɫɬɢɦɚ ɤɨɪɢɝɨɜɚɧɟ ɤɨɧɰɟɧɬɪɚɰɢʁɟ uAQP-1.0 ɢɡɦɟђɭ ɤɚɬɟɝɨɪɢʁɚ ɩɚɬɨɥɨɲɤɢɯ ɫɬɚɞɢʁɭɦɚ ɬɭɦɨɪɚ, ɚ ɬɨ ʁɟ ɩɨɬɜɪђɟɧɨ ɢ ɬɟɫɬɢɪɚʃɟɦ ɩɚɪɨɜɚ ɤɚɬɟɝɨɪɢʁɚ ɩɚɬɨɥɨɲɤɢɯ ɫɬɚɞɢʁɭɦɚ ɬɭɦɨɪɚ, ɲɬɨ ɫɟ ɦɨɠɟ ɜɢɞɟɬɢ ɢɡ ɬɚɛɟɥɟ ɛɪ. 69. Ɍɚɛɟɥɚ ɛɪ. 69. Ɋɟɡɭɥɬɚɬɢ ɬɟɫɬɢɪɚʃɚ ɜɪɟɞɧɨɫɬɢuAQP-1.0(ng/mgUcr) ɩɨ ɩɚɪɨɜɢɦɚ ɤɚɬɟɝɨɪɢʁɚ ɩɚɬɨɥɨɲɤɢɯ ɫɬɚɞɢʁɭɦɚ ɬɭɦɨɪɚ ɉɚɪɨɜɢ ɤɚɬɟɝɨɪɢʁɚ ɩɚɬɨɥɨɲɤɢɯ ɫɬɚɞɢʁɭɦɚ ɬɭɦɨɪɚ Wilcox rank sum test with continuity correction 1ɚ vs 1ɛ W= 83; p*= 0.277 1ɚ vs 2ɚ W= 19; p*= 1 1ɚ vs 3ɚ W= 92; p*= 0.719 1ɛ vs 2ɚ W= 10; p*= 0.468 1ɛ vs 3ɚ W= 53.5; p*= 0.495 2ɚ vs 3ɚ W=22.5; p*=0.736 *BonПОrronТ ɤɨɪɟɤцɢјɚ: 0.05/6=0.0083 Ɉɞ ɢɧɬɟɪɟɫɚ ɡɚ ɢɫɬɪɚɠɢɜɚʃɟ ɛɢɥɨ ʁɟ ɢɫɩɢɬɢɜɚʃɟ ɜɪɟɞɧɨɫɬɢ ɚɩɫɨɥɭɬɧɟ ɤɨɧɰɟɧɬɪɚɰɢʁɟ AQP-1 ɭ ɭɪɢɧɭ ɩɪɟ ɨɩɟɪɚɰɢʁɟ, ɨɡɧɚɱɟɧɨ ɤɚɨ uAQP-1.0 (ng/ml), ɭ ɨɞɧɨɫɭ ɧɚ ɤɚɬɟɝɨɪɢʁɟ ɯɢɫɬɨɥɨɲɤɨɝ ɝɪɚɞɭɫɚ ɬɭɦɨɪɚ. Ⱦɟɫɤɪɢɩɬɢɜɧɢ ɩɨɞɚɰɢ ɢ ɪɟɡɭɥɬɚɬɢ ɬɟɫɬɢɪɚʃɚ ɩɪɢɤɚɡɚɧɢ ɫɭ ɭ ɬɚɛɟɥɢ ɛɪ. 70. ɊȿɁɍɅɌȺɌɂ 76 Ɍɚɛɟɥɚ ɛɪ. 70. Ⱦɟɫɤɪɢɩɬɢɜɧɢ ɩɨɞɚɰɢ ɤɨɧɰɟɧɬɪɚɰɢʁɟ uAQP-1.0(nР/ml) ɭ ɨɞɧɨɫɭ ɧɚ ɤɚɬɟɝɨɪɢʁɟ ɯɢɫɬɨɥɨɲɤɨɝ ɝɪɚɞɭɫɚ ɬɭɦɨɪɚ ɢ ɪɟɡɭɥɬɚɬɢ ɬɟɫɬɢɪɚʃɚ uAQP-1.0 Ʉɚɬɟɝɨɪɢʁɟ ɯɢɫɬɨɥɨɲɤɨɝ ɝɪɚɞɭɫɚ ɬɭɦɨɪɚ Kruskal Wallis-ɨɜ ɬɟɫɬ G2 (1) G3 (2) G4 (3) N (%) 30 (100%) 8 (100%) 1 (100%) χ22=2.107; p= 0.349 ɉɪɨɫɟɤ (ɋȾ) Ɇɟɞɢʁɚɧɚ (ɨɩɫɟɝ) Ȼɟɡ ɩɨɞɚɬɚɤɚ 0.09 (0.05) 0.0855 (0-0.287) 2 (6.67%) 0.11 (0.04) 0.09 (0.082-0.207) - 0.09 (-) 0.089 (0.089-0.089) - Ʉɚɨ ɲɬɨ ɫɟ ɢɡ ɬɚɛɟɥɟ ɛɪ. 70. ɜɢɞɢ, ɧɟ ɩɨɫɬɨʁɢ ɫɬɚɬɢɫɬɢɱɤɢ ɡɧɚɱɚʁɧɚ ɪɚɡɥɢɤɚ ɭ ɜɪɟɞɧɨɫɬɢɦɚ ɚɩɫɨɥɭɬɧɟ ɤɨɧɰɟɧɬɪɚɰɢʁɟ uAQP-1.0 ɢɡɦɟђɭ ɤɚɬɟɝɨɪɢʁɚ ɯɢɫɬɨɥɨɲɤɨɝ ɝɪɚɞɭɫɚ ɬɭɦɨɪɚ. Ɍɟɫɬɢɪɚʃɟɦ ɩɚɪɨɜɚ ɤɚɬɟɝɨɪɢʁɚ ɯɢɫɬɨɥɨɲɤɢɯ ɝɪɚɞɭɫɚ ɬɭɦɨɪɚ ɞɨɛɢʁɟɧɢ ɫɭ ɩɨɞɚɰɢ ɩɪɢɤɚɡɚɧɢ ɭ ɬɚɛɟɥɢ ɛɪ. 71. Ɍɚɛɟɥɚ ɛɪ. 71. Ɋɟɡɭɥɬɚɬɢ ɬɟɫɬɢɪɚʃɚ ɜɪɟɞɧɨɫɬɢ uAQP-1.0(nР/ml) ɩɨ ɩɚɪɨɜɢɦɚ ɤɚɬɟɝɨɪɢʁɚ ɯɢɫɬɨɥɨɲɤɨɝ ɝɪɚɞɭɫɚ ɬɭɦɨɪɚ ɉɚɪɨɜɢ ɤɚɬɟɝɨɪɢʁɚ ɯɢɫɬɨɥɨɲɤɨɝ ɝɪɚɞɭɫɚ ɬɭɦɨɪɚ Wilcox rank sum test with continuity correction G2vs G3 W= 79.5; p*=0.151 G2 vs G4 W= 12.5; p*=0.1294 G3 vs G4 W= 4; p*=1 *Bonferroni korekcija: 0.05/3=0.0167 Ʉɚɨ ɲɬɨ ɫɟ ɜɢɞɢ ɢɡ ɬɚɛɟɥɟ ɛɪ. 71., ɬɟɫɬɢɪɚʃɟɦ ɜɪɟɞɧɨɫɬɢ uAQP-1.0 (ng/ml) ɩɨ ɩɚɪɨɜɢɦɚ ɤɚɬɟɝɨɪɢʁɚ ɯɢɫɬɨɥɨɲɤɨɝ ɝɪɚɞɭɫɚ ɬɭɦɨɪɚ ɧɢʁɟ ɞɨɛɢʁɟɧɚ ɫɬɚɬɢɫɬɢɱɤɢ ɡɧɚɱɚʁɧɚ ɪɚɡɥɢɤɚ ɢɡɦɟђɭ ɩɚɪɨɜɚ. ɍ ɬɚɛɟɥɢ ɛɪ. 72. ɩɪɢɤɚɡɚɧɟ ɫɭ ɤɨɪɢɝɨɜɚɧɟ ɤɨɧɰɟɧɬɪɚɰɢʁɟ uAQP-1ɭ ɭɪɢɧɭ ɩɪɟ ɨɩɟɪɚɰɢʁɟ, uAQP-1.0 (ng/mgUcr) ɭ ɨɞɧɨɫɭ ɧɚ ɤɚɬɟɝɨɪɢʁɟ ɯɢɫɬɨɥɨɲɤɨɝ ɝɪɚɞɭɫɚ ɬɭɦɨɪɚ. Ɍɚɛɟɥɚ ɛɪ. 72. Ⱦɟɫɤɪɢɩɬɢɜɧɢ ɩɨɞɚɰɢ ɤɨɧɰɟɧɬɪɚɰɢʁɟ uAQP-1.0(ng/mgUcr) ɭ ɨɞɧɨɫɭ ɧɚ ɤɚɬɟɝɨɪɢʁɟɯɢɫɬɨɥɨɲɤɨɝ ɝɪɚɞɭɫɚ ɬɭɦɨɪɚ ɢ ɪɟɡɭɥɬɚɬɢ ɬɟɫɬɢɪɚʃɚ uAQP-1.0 Ʉɚɬɟɝɨɪɢʁɟ ɯɢɫɬɨɥɨɲɤɨɝ ɝɪɚɞɭɫɚ ɬɭɦɨɪɚ Kruskal Wallis-ɨɜ ɬɟɫɬ G2 (1) G3 (2) G4 (3) N (%) 30 (100%) 8 (100%) 1 (100%) χ22=1.206; p= 0.547 ɉɪɨɫɟɤ (ɋȾ) Ɇɟɞɢʁɚɧɚ (ɨɩɫɟɝ) Ȼɟɡ ɩɨɞɚɬɚɤɚ 0.11 (0.1) 0.077 (0-0.412) 2 (6.67%) 0.1 (0.07) 0.08 (0.037-0.239) - 0.04 (-) 0.041 (0.041-0.041) - Ʉɚɨ ɲɬɨ ɫɟ ɢɡ ɬɚɛɟɥɟ ɛɪ. 72. ɜɢɞɢ, ɧɟ ɩɨɫɬɨʁɢ ɫɬɚɬɢɫɬɢɱɤɢ ɡɧɚɱɚʁɧɚ ɪɚɡɥɢɤɚ ɭ ɜɪɟɞɧɨɫɬɢɦɚ ɤɨɪɢɝɨɜɚɧɟ ɤɨɧɰɟɧɬɪɚɰɢʁɟ uAQP-1.0 ɢɡɦɟђɭ ɤɚɬɟɝɨɪɢʁɚ ɯɢɫɬɨɥɨɲɤɨɝ ɝɪɚɞɭɫɚ ɬɭɦɨɪɚ. Ɍɟɫɬɢɪɚʃɟɦ ɩɚɪɨɜɚ ɤɚɬɟɝɨɪɢʁɚ ɯɢɫɬɨɥɨɲɤɢɯ ɝɪɚɞɭɫɚ ɬɭɦɨɪɚ ɞɨɛɢʁɟɧɢ ɫɭ ɩɨɞɚɰɢ ɩɪɢɤɚɡɚɧɢ ɭ ɬɚɛɟɥɢ ɛɪ. 73. ɊȿɁɍɅɌȺɌɂ 77 Ɍɚɛɟɥɚ ɛɪ. 73. Ɋɟɡɭɥɬɚɬɢ ɬɟɫɬɢɪɚʃɚ ɜɪɟɞɧɨɫɬɢ uAQP-1.0(ng/mgUcr) ɩɨ ɩɚɪɨɜɢɦɚ ɤɚɬɟɝɨɪɢʁɚ ɯɢɫɬɨɥɨɲɤɨɝ ɝɪɚɞɭɫɚ ɬɭɦɨɪɚ ɉɚɪɨɜɢ ɤɚɬɟɝɨɪɢʁɚ ɯɢɫɬɨɥɨɲɤɨɝ ɝɪɚɞɭɫɚ ɬɭɦɨɪɚ Wilcox rank sum test with continuity correction G2vs G3 W= 113; p*=0.816 G2 vs G4 W= 24; p*=0.342 G3 vs G4 W= 7; p*=0.331 *Bonferroni korekcija: 0.05/3=0.0167 Ʉɚɨ ɲɬɨ ɫɟ ɜɢɞɢ ɢɡ ɬɚɛɟɥɟ ɛɪ. 73., ɬɟɫɬɢɪɚʃɟɦ ɜɪɟɞɧɨɫɬɢ uAQP-1.0 (ng/mgUcr) ɩɨ ɩɚɪɨɜɢɦɚ ɤɚɬɟɝɨɪɢʁɚ ɯɢɫɬɨɥɨɲɤɨɝ ɝɪɚɞɭɫɚ ɬɭɦɨɪɚ ɧɢʁɟ ɞɨɛɢʁɟɧɚ ɫɬɚɬɢɫɬɢɱɤɢ ɡɧɚɱɚʁɧɚ ɪɚɡɥɢɤɚ ɢɡɦɟђɭ ɩɚɪɨɜɚ. ɍ ɢɫɬɪɚɠɢɜɚʃɭ ʁɟ ɫɩɪɨɜɟɞɟɧɨ ɢɫɩɢɬɢɜɚʃɟ ɜɪɟɞɧɨɫɬɢ ɚɩɫɨɥɭɬɧɟ ɤɨɧɰɟɧɬɪɚɰɢʁɟ AQP-1 ɭ ɭɪɢɧɭ ɩɪɟ ɨɩɟɪɚɰɢʁɟ, ɨɡɧɚɱɟɧɨ ɤɚɨ uAQP-1.0 (ng/ml), ɭ ɨɞɧɨɫɭ ɧɚ ɤɚɬɟɝɨɪɢʁɟ ɥɢɦɮɧɨ- ɜɚɫɤɭɥɚɪɧɟ ɢɧɜɚɡɢʁɟ. Ⱦɟɫɤɪɢɩɬɢɜɧɢ ɩɨɞɚɰɢ ɢ ɪɟɡɭɥɬɚɬɢ ɬɟɫɬɢɪɚʃɚ ɩɪɢɤɚɡɚɧɢ ɫɭ ɭ ɬɚɛɟɥɢ ɛɪ. 74. Ɍɚɛɟɥɚ ɛɪ. 74. Ⱦɟɫɤɪɢɩɬɢɜɧɢ ɩɨɞɚɰɢ ɤɨɧɰɟɧɬɪɚɰɢʁɟ uAQP-1.0 (nР/ml) ɭ ɨɞɧɨɫɭ ɧɚ ɤɚɬɟɝɨɪɢʁɟ ɥɢɦɮɧɨ-ɜɚɫɤɭɥɚɪɧɟ ɢɧɜɚɡɢʁɟ ɢ ɪɟɡɭɥɬɚɬɢ ɬɟɫɬɢɪɚʃɚ uAQP-1.0 Ʉɚɬɟɝɨɪɢʁɟ ɬɭɦɨɪɫɤɟ ɥɢɦɮɧɨ-ɜɚɫɤɭɥɚɪɧɟ ɢɧɜɚɡɢʁɟ Kruskal Wallis-ɨɜ ɬɟɫɬ L0V0 (1) L0V1 (L1V0) (2) L1V1 (3) N (%) 7 (100%) 13 (100%) 19 (100%) χ22=0.686; p= 0.709 ɉɪɨɫɟɤ (ɋȾ) Ɇɟɞɢʁɚɧɚ (ɨɩɫɟɝ) Ȼɟɡ ɩɨɞɚɬɚɤɚ 0.07 (0.03) 0.085 (0-0.103) - 0.1 (0.03) 0.086 (0.073-0.2) - 0.1 (0.05) 0.086 (0.074-0.287) 2 (10.53%) Ʉɚɨ ɲɬɨ ɫɟ ɢɡ ɬɚɛɟɥɟ ɛɪ. 74. ɜɢɞɢ, ɧɟ ɩɨɫɬɨʁɢ ɫɬɚɬɢɫɬɢɱɤɢ ɡɧɚɱɚʁɧɚ ɪɚɡɥɢɤɚ ɭ ɜɪɟɞɧɨɫɬɢɦɚ ɚɩɫɨɥɭɬɧɟ ɤɨɧɰɟɧɬɪɚɰɢʁɟ uAQP-1.0 ɢɡɦɟђɭ ɤɚɬɟɝɨɪɢʁɚ ɥɢɦɮɧɨ-ɜɚɫɤɭɥɚɪɧɟ ɢɧɜɚɡɢʁɟ. Ⱦɨɞɚɬɧɢɦ ɬɟɫɬɢɪɚʃɟɦ ɞɨɛɢʁɟɧɢ ɫɭ ɪɟɡɭɥɬɚɬɢ ɩɪɢɤɚɡɚɧɢ ɭ ɬɚɛɟɥɢ ɛɪ. 75. Ɍɚɛɟɥɚ ɛɪ. 75. Ɋɟɡɭɥɬɚɬɢ ɬɟɫɬɢɪɚʃɚ ɜɪɟɞɧɨɫɬɢ uAQP-1.0(nР/ml) ɩɨ ɩɚɪɨɜɢɦɚ ɤɚɬɟɝɨɪɢʁɚɥɢɦɮɧɨ-ɜɚɫɤɭɥɚɪɧɟ ɢɧɜɚɡɢʁɟ ɉɚɪɨɜɢ ɤɚɬɟɝɨɪɢʁɚ ɥɢɦɮɧɨ-ɜɚɫɤɭɥɚɪɧɟ ɢɧɜɚɡɢʁɟ Wilcox rank sum test with continuity correction L0V0 vs L0V1 (L1V0) W= 37; p*= 0.525 L0V0 vs L1V1 W= 53; p*= 0.451 L0V1 (L1V0) vs L1V1 W= 118; p*= 0.847 *Bonferroni korekcija: 0.05/3=0.0167 Ʉɚɨ ɲɬɨ ɫɟ ɜɢɞɢ ɢɡ ɬɚɛɟɥɟ ɛɪ. 75., ɬɟɫɬɢɪɚʃɟɦ ɜɪɟɞɧɨɫɬɢ uAQP-1.0 (ng/ml) ɩɨ ɩɚɪɨɜɢɦɚ ɤɚɬɟɝɨɪɢʁɚ ɬɭɦɨɪɫɤɟ ɥɢɦɮɧɨ-ɜɚɫɤɭɥɚɪɧɟ ɢɧɜɚɡɢʁɟ, ɧɢʁɟ ɞɨɛɢʁɟɧɚ ɫɬɚɬɢɫɬɢɱɤɢ ɡɧɚɱɚʁɧɚ ɪɚɡɥɢɤɚ ɢɡɦɟђɭ ɩɚɪɨɜɚ. ɊȿɁɍɅɌȺɌɂ 78 Ⱦɟɫɤɪɢɩɬɢɜɧɢ ɩɨɞɚɰɢ ɢ ɪɟɡɭɥɬɚɬɢ ɬɟɫɬɢɪɚʃɚ ɤɨɪɢɝɨɜɚɧɟ ɤɨɧɰɟɧɬɪɚɰɢʁɟ uAQP-1ɭ ɭɪɢɧɭ ɩɪɟ ɨɩɟɪɚɰɢʁɟ, uAQP-1.0 (ng/mgUcr), ɭ ɨɞɧɨɫɭ ɧɚ ɤɚɬɟɝɨɪɢʁɟ ɥɢɦɮɧɨ-ɜɚɫɤɭɥɚɪɧɟ ɢɧɜɚɡɢʁɟ ɩɪɢɤɚɡɚɧɢ ɫɭ ɭ ɬɚɛɟɥɢ ɛɪ. 76. Ɍɚɛɟɥɚ ɛɪ. 76. Ⱦɟɫɤɪɢɩɬɢɜɧɢ ɩɨɞɚɰɢ ɤɨɧɰɟɧɬɪɚɰɢʁɟ uAQP-1.0 (ng/mgUcr) ɭ ɨɞɧɨɫɭ ɧɚ ɤɚɬɟɝɨɪɢʁɟɥɢɦɮɧɨ-ɜɚɫɤɭɥɚɪɧɟ ɢɧɜɚɡɢʁɟ ɢ ɪɟɡɭɥɬɚɬɢ ɬɟɫɬɢɪɚʃɚ uAQP-1.0 Ʉɚɬɟɝɨɪɢʁɟ ɬɭɦɨɪɫɤɟ ɥɢɦɮɧɨ-ɜɚɫɤɭɥɚɪɧɟ ɢɧɜɚɡɢʁɟ Kruskal Wallis-ɨɜ ɬɟɫɬ L0V0 (1) L0V1 (L1V0) (2) L1V1 (3) N (%) 7 (100%) 13 (100%) 19 (100%) χ22=0.851; p= 0.653 ɉɪɨɫɟɤ (ɋȾ) Ɇɟɞɢʁɚɧɚ (ɨɩɫɟɝ) Ȼɟɡ ɩɨɞɚɬɚɤɚ 0.12 (0.15) 0.069 (0-0.412) - 0.11 (0.1) 0.067 (0.026-0.315) - 0.1 (0.06) 0.08 (0.037-0.248) 2 (10.53%) Ʉɚɨ ɲɬɨ ɫɟ ɢɡ ɬɚɛɟɥɟ ɛɪ. 76. ɜɢɞɢ, ɧɟ ɩɨɫɬɨʁɢ ɫɬɚɬɢɫɬɢɱɤɢ ɡɧɚɱɚʁɧɚ ɪɚɡɥɢɤɚ ɭ ɜɪɟɞɧɨɫɬɢɦɚ ɤɨɪɢɝɨɜɚɧɟ ɤɨɧɰɟɧɬɪɚɰɢʁɟ uAQP-1.0 ɢɡɦɟђɭ ɤɚɬɟɝɨɪɢʁɚ ɬɭɦɨɪɫɤɟ ɥɢɦɮɧɨ-ɜɚɫɤɭɥɚɪɧɟ ɢɧɜɚɡɢʁɟ, ɲɬɨ ʁɟ ɩɨɬɜɪђɟɧɨ ɢ ɬɟɫɬɢɪɚʃɟɦ ɩɚɪɨɜɚ ɤɚɬɟɝɨɪɢʁɚ ɬɭɦɨɪɫɤɟ ɥɢɦɮɧɨ-ɜɚɫɤɭɥɚɪɧɟ ɢɧɜɚɡɢʁɟ (ɬɚɛɟɥɚ ɛɪ. 77.). Ɍɚɛɟɥɚ ɛɪ. 77. Ɋɟɡɭɥɬɚɬɢ ɬɟɫɬɢɪɚʃɚ ɜɪɟɞɧɨɫɬɢ uAQP-1.0(ng/mgUcr) ɩɨ ɩɚɪɨɜɢɦɚ ɤɚɬɟɝɨɪɢʁɚ ɬɭɦɨɪɫɤɟ ɥɢɦɮɧɨ-ɜɚɫɤɭɥɚɪɧɟ ɢɧɜɚɡɢʁɟ ɉɚɪɨɜɢ ɤɚɬɟɝɨɪɢʁɚ ɥɢɦɮɧɨ-ɜɚɫɤɭɥɚɪɧɟ ɢɧɜɚɡɢʁɟ Wilcox rank sum test with continuity correction L0V0 vs L0V1 (L1V0) W= 37.5; p*= 0.551 L0V0 vs L1V1 W= 49.5; p*= 0.340 L0V1 (L1V0) vs L1V1 W= 122; p*= 0.969 *Bonferroni korekcija: 0.05/3=0.0167 ɍ ɢɫɬɪɚɠɢɜɚʃɭ ʁɟ ɫɩɪɨɜɟɞɟɧɨ ɢɫɩɢɬɢɜɚʃɟ ɜɪɟɞɧɨɫɬɢ ɚɩɫɨɥɭɬɧɟ ɤɨɧɰɟɧɬɪɚɰɢʁɟ uAQP-1 ɭ ɭɪɢɧɭ ɩɪɟ ɨɩɟɪɚɰɢʁɟ, ɨɡɧɚɱɟɧɨ ɤɚɨ uAQP-1(ng/ml), ɭ ɨɞɧɨɫɭ ɧɚ ɤɚɬɟɝɨɪɢʁɟ ɩɨɫɬɨɩɟɪɚɬɢɜɧɨɝ TNM ɫɬɚɞɢʁɭɦɚ. Ⱦɟɫɤɪɢɩɬɢɜɧɢ ɩɨɞɚɰɢ ɢ ɪɟɡɭɥɬɚɬɢ ɬɟɫɬɢɪɚʃɚ ɩɪɢɤɚɡɚɧɢ ɫɭ ɭ ɬɚɛɟɥɢ ɛɪ. 78. Ɍɚɛɟɥɚ ɛɪ. 78. Ⱦɟɫɤɪɢɩɬɢɜɧɢ ɩɨɞɚɰɢ ɤɨɧɰɟɧɬɪɚɰɢʁɟ uAQP-1 (nР/ml) ɭ ɨɞɧɨɫɭ ɧɚ ɤɚɬɟɝɨɪɢʁɟ ɩɨɫɬɨɩɟɪɚɬɢɜɧɨɝ TNM ɫɬɚɞɢʁɭɦɚ ɢ ɪɟɡɭɥɬɚɬɢ ɬɟɫɬɢɪɚʃɚ uAQP-1 Ʉɚɬɟɝɨɪɢʁɟ ɩɨɫɬɨɩɟɪɚɬɢɜɧɨɝ TNM ɫɬɚɞɢʁɭɦɚ Kruskal Wallis-ɨɜ ɬɟɫɬ I (1) II (2) III (3) IV(4) N (%) 22 (100%) 3 (100%) 12 (100%) 2 (100%) ɉɪɨɫɟɤ (ɋȾ) 0.09 (0.03) 0.09 (0.01) 0.11 (0.07) 0.1 (0.03) χ 2 2=1.604; p= 0.658 Ɇɟɞɢʁɚɧɚ (ɨɩɫɟɝ) 0.083 (0-0.2) 0.09 (0.077-0.094) 0.086 (0.075-0.287) 0.103 (0.085-0.122) Ȼɟɡ ɩɨɞɚɬɚɤɚ 1 (4.35%) - 1 (7.69%) - ɊȿɁɍɅɌȺɌɂ 79 ɂɡ ɬɚɛɟɥɟ ɛɪ. 78. ɫɟ ɜɢɞɢ ɞɚ ɧɟ ɩɨɫɬɨʁɢ ɫɬɚɬɢɫɬɢɱɤɢ ɡɧɚɱɚʁɧɚ ɪɚɡɥɢɤɚ ɭ ɜɪɟɞɧɨɫɬɢɦɚ ɚɩɫɨɥɭɬɧɟ ɤɨɧɰɟɧɬɪɚɰɢʁɟ uAQP-1.0 ɢɡɦɟђɭ ɤɚɬɟɝɨɪɢʁɚ ɩɨɫɬɨɩɟɪɚɬɢɜɧɨɝ TNM ɫɬɚɞɢʁɭɦɚ. Ⱦɨɞɚɬɧɢɦ ɬɟɫɬɢɪɚʃɟɦ ɞɨɛɢʁɟɧɢ ɫɭ ɪɟɡɭɥɬɚɬɢ ɩɪɢɤɚɡɚɧɢ ɭ ɬɚɛɟɥɢ ɛɪ. 79. Ɍɚɛɟɥɚ ɛɪ. 79. Ɋɟɡɭɥɬɚɬɢ ɬɟɫɬɢɪɚʃɚ ɜɪɟɞɧɨɫɬɢ ɚɩɫɨɥɭɬɧɟ ɤɨɧɰɟɧɬɪɚɰɢʁɟ uAQP-1.0(nР/ml) ɩɨ ɩɚɪɨɜɢɦɚ ɤɚɬɟɝɨɪɢʁɚ ɩɨɫɬɨɩɟɪɚɬɢɜɧɨɝ TNM ɫɬɚɞɢʁɭɦɚ ɉɚɪɨɜɢ ɤɚɬɟɝɨɪɢʁɚ ɩɚɬɨɥɨɲɤɢɯ ɫɬɚɞɢʁɭɦɚ ɬɭɦɨɪɚ Wilcox rank sum test with continuity correction I vs II W= 29.5; p*= 0.802 I vs III W= 106.5; p*= 0.366 I vs IV W= 11.5; p*= 0.295 II vs III W= 19.5; p*= 0.885 II vs IV W=2; p*=0.8 III vs IV W=4; p*= 0.783 *BonПОrronТ ɤɨɪɟɤцɢјɚ: 0.05/6=0.0083 Ɍɟɫɬɢɪɚʃɟɦ ɩɚɪɨɜɚ ɤɚɬɟɝɨɪɢʁɚ ɩɨɫɬɨɩɟɪɚɬɢɜɧɨɝ TNM ɫɬɚɞɢʁɭɦɚ ɧɢʁɟ ɞɨɛɢʁɟɧɚ ɫɬɚɬɢɫɬɢɱɤɢ ɡɧɚɱɚʁɧɚ ɪɚɡɥɢɤɚ ɢɡɦɟђɭ ɩɚɪɨɜɚ (ɬɚɛɟɥɚ ɛɪ. 79.). Ⱦɟɫɤɪɢɩɬɢɜɧɢ ɩɨɞɚɰɢ ɢ ɪɟɡɭɥɬɚɬɢ ɬɟɫɬɢɪɚʃɚ ɤɨɪɢɝɨɜɚɧɟ ɤɨɧɰɟɧɬɪɚɰɢʁɟ uAQP-1 ɭ ɭɪɢɧɭ ɩɪɟ ɨɩɟɪɚɰɢʁɟ, uAQP-1.0 (ng/mgUcr), ɭ ɨɞɧɨɫɭ ɧɚ ɤɚɬɟɝɨɪɢʁɟ ɩɨɫɬɨɩɟɪɚɬɢɜɧɨɝ TNM ɫɬɚɞɢʁɭɦɚ ɩɪɢɤɚɡɚɧɢ ɫɭ ɭ ɬɚɛɟɥɢ ɛɪ. 80. Ɍɚɛɟɥɚ ɛɪ. 80. Ⱦɟɫɤɪɢɩɬɢɜɧɢ ɩɨɞɚɰɢ ɤɨɪɢɝɨɜɚɧɟ ɤɨɧɰɟɧɬɪɚɰɢʁɟ uAQP-1 (ng/mgUcr) ɭ ɨɞɧɨɫɭ ɧɚ ɤɚɬɟɝɨɪɢʁɟɩɨɫɬɨɩɟɪɚɬɢɜɧɨɝ TNM ɫɬɚɞɢʁɭɦɚ ɢ ɪɟɡɭɥɬɚɬɢ ɬɟɫɬɢɪɚʃɚ uAQP-1 Ʉɚɬɟɝɨɪɢʁɟ ɩɨɫɬɨɩɟɪɚɬɢɜɧɨɝ TNM ɫɬɚɞɢʁɭɦɚ Kruskal Wallis-ɨɜ ɬɟɫɬ I (1) II (2) III (3) IV(4) N (%) 22 (100%) 3 (100%) 12 (100%) 2 (100%) ɉɪɨɫɟɤ (ɋȾ) 0.11 (0.11) 0.13 (0.11) 0.09 (0.05) 0.16 (0.11) χ 2 2=1.136; p= 0.768 Ɇɟɞɢʁɚɧɚ (ɨɩɫɟɝ) 0.072 (0-0.412) 0.101 (0.037-0.248) 0.077 (0.037-0.175) 0.159 (0.08-0.239) Ȼɟɡ ɩɨɞɚɬɚɤɚ 1 (4.35%) - 1 (7.69%) - ɂɡ ɬɚɛɟɥɟ ɛɪ. 80. ɫɟ ɜɢɞɢ ɞɚ ɧɟ ɩɨɫɬɨʁɢ ɫɬɚɬɢɫɬɢɱɤɢ ɡɧɚɱɚʁɧɚ ɪɚɡɥɢɤɚ ɭ ɜɪɟɞɧɨɫɬɢɦɚ ɤɨɪɢɝɨɜɚɧɟ ɤɨɧɰɟɧɬɪɚɰɢʁɟ uAQP-1.0 ɢɡɦɟђɭ ɤɚɬɟɝɨɪɢʁɚ ɩɨɫɬɨɩɟɪɚɬɢɜɧɨɝ TNM ɫɬɚɞɢʁɭɦɚ. Ⱦɨɞɚɬɧɢɦ ɬɟɫɬɢɪɚʃɟɦ ɞɨɛɢʁɟɧɢ ɫɭ ɪɟɡɭɥɬɚɬɢ ɩɪɢɤɚɡɚɧɢ ɭ ɬɚɛɟɥɢ ɛɪ. 81. Ɍɚɛɟɥɚ ɛɪ. 81. Ɋɟɡɭɥɬɚɬɢ ɬɟɫɬɢɪɚʃɚ ɜɪɟɞɧɨɫɬɢ uAQP-1.0 (ng/mgUcr) ɩɨ ɩɚɪɨɜɢɦɚ ɤɚɬɟɝɨɪɢʁɚ ɩɨɫɬɨɩɟɪɚɬɢɜɧɨɝ TNM ɫɬɚɞɢʁɭɦɚ ɉɚɪɨɜɢ ɤɚɬɟɝɨɪɢʁɚ ɩɚɬɨɥɨɲɤɢɯ ɫɬɚɞɢʁɭɦɚ ɬɭɦɨɪɚ Wilcox rank sum test with continuity correction I vs II W= 27; p*= 0.645 I vs III W= 126.5; p*= 0.857 I vs IV W= 14; p*= 0.433 II vs III W= 20.5; p*= 0.773 II vs IV W=3; p*=1 III vs IV W=5.5; p*= 0.273 *BonПОrronТ ɤɨɪɟɤцɢјɚ: 0.05/6=0.0083 ɊȿɁɍɅɌȺɌɂ 80 Ɍɟɫɬɢɪɚʃɟɦ ɤɨɪɢɝɨɜɚɧɟ ɤɨɧɰɟɧɬɪɚɰɢʁɟ uAQP-1.0 (ng/mgUcr) ɩɨ ɩɚɪɨɜɢɦɚ ɤɚɬɟɝɨɪɢʁɚ ɩɨɫɬɨɩɟɪɚɬɢɜɧɨɝ TNM ɫɬɚɞɢʁɭɦɚ, ɧɢʁɟ ɞɨɛɢʁɟɧɚ ɫɬɚɬɢɫɬɢɱɤɢ ɡɧɚɱɚʁɧɚ ɪɚɡɥɢɤɚ ɢɡɦɟђɭ ɩɚɪɨɜɚ (ɬɚɛɟɥɚ ɛɪ. 81.). 4.5. ɂɫɩɢɬɢɜɚʃɟ ɩɨɜɟɡɚɧɨɫɬɢ uKIM-1ɢ uAQP-1 ɢɜɪɫɬɟ ɨɩɟɪɚɬɢɜɧɨɝ ɥɟɱɟʃɚ ɭ ɝɪɭɩɢ ɨɛɨɥɟɥɢɯ 4.5.1. ɂɫɩɢɬɢɜɚʃɟ ɩɨɜɟɡɚɧɨɫɬɢ uKIM-1 ɢ ɜɪɫɬɟ ɨɩɟɪɚɬɢɜɧɨɝ ɥɟɱɟʃɚ Ɉɞ ɢɧɬɟɪɟɫɚ ɡɚ ɢɫɬɪɚɠɢɜɚʃɟ ɛɢɥɨ ʁɟ ɢɫɩɢɬɢɜɚʃɟ ɩɨɜɟɡɚɧɨɫɬɢ ɩɪɟɨɩɟɪɚɬɢɜɧɟ ɜɪɟɞɧɨɫɬɢ uKIM-1, ɨɡɧɚɱɟɧɨ ɤɚɨ uKIM-1.0 ɢ ɬɢɩɚ ɧɟɮɪɟɤɬɨɦɢʁɟ. ɍ ɬɚɛɟɥɢ ɛɪ. 82. ɧɚɜɟɞɟɧɢ ɫɭ ɞɟɫɤɪɢɩɬɢɜɧɢ ɩɨɞɚɰɢ ɨ ɜɪɟɞɧɨɫɬɢ ɚɩɫɨɥɭɬɧɟ ɤɨɧɰɟɧɬɪɚɰɢʁɟ uKIM-1.0 (ng/ml) ɢ ɬɢɩɚ ɧɟɮɪɟɤɬɨɦɢʁɟ. Ɍɚɛɟɥɚ ɛɪ. 82. Ⱦɟɫɤɪɢɩɬɢɜɧɢ ɩɨɞɚɰɢ ɤɨɧɰɟɧɬɪɚɰɢʁɟ uKIM-1.0 (nР/ml) ɭ ɨɞɧɨɫɭ ɧɚ ɬɢɩ ɧɟɮɪɟɤɬɨɦɢʁɟ ɢ ɪɟɡɭɥɬɚɬɢ ɬɟɫɬɢɪɚʃɚ Ⱦɟɫɤɪɢɩɬɢɜɧɢ ɩɨɞɚɰɢ ȼɪɟɞɧɨɫɬɢ uKIM-1.0 ɉɚɪɰɢʁɚɥɧɚ ɧɟɮɪɟɤɬɨɦɢʁɚ Ɋɚɞɢɤɚɥɧɚ ɧɟɮɪɟɤɬɨɦɢʁɚ N(%) 8 (100%) 32 (100%) ɉɪɨɫɟɤ (ɋȾ) 0.26 (0.17) 1.21 (1.61) Ɇɟɞɢʁɚɧɚ (ɨɩɫɟɝ) 0.261 (0.038-0.459) 0.37 (0.091-5) Ȼɟɡ ɩɨɞɚɬɚɤɚ - 1 (3%) Wilcoxon rank sum test with continuity correction: W= 75; p= 0.076 Ʉɚɨ ɲɬɨ ɫɟ ɜɢɞɢ ɢɡ ɬɚɛɟɥɟ ɛɪ. 82., ɩɪɟɨɩɟɪɚɬɢɜɧɚ ɜɪɟɞɧɨɫɬ ɚɩɫɨɥɭɬɧɟ ɤɨɧɰɟɧɬɪɚɰɢʁɟ uKIM-1 ɭ ɝɪɭɩɢ ɩɚɰɢʁɟɧɚɬɚ ɤɨɞ ɤɨʁɢɯ ʁɟ ɫɩɪɨɜɟɞɟɧɚ ɪɚɞɢɤɚɥɧɚ ɧɟɮɪɟɤɬɨɦɢʁɚ ʁɟ ɜɢɲɚ ɭ ɨɞɧɨɫɭ ɧɚ ɝɪɭɩɭ ɫɚ ɩɚɪɰɢʁɚɥɧɨɦ ɧɟɮɪɟɤɬɨɦɢʁɨɦ ɚɥɢ ɛɟɡ ɫɬɚɬɢɫɬɢɱɤɟ ɡɧɚɱɚʁɧɨɫɬɢ (p=0.076). ɂɫɬɢ ɨɛɥɢɤ ɬɟɫɬɢɪɚʃɚ ɫɩɪɨɜɟɞɟɧ ʁɟ ɢ ɡɚ ɤɨɪɢɝɨɜɚɧɭ ɤɨɧɰɟɧɬɪɚɰɢʁɭ uKIM-1, uKIM-1.0 (ng/mgUcr), ɚ ɪɟɡɭɥɬɚɬɢ ɫɭ ɩɪɢɤɚɡɚɧɢ ɭ ɬɚɛɟɥɢ 83. Ɍɚɛɟɥɚ ɛɪ. 83. Ⱦɟɫɤɪɢɩɬɢɜɧɢ ɩɨɞɚɰɢ ɤɨɧɰɟɧɬɪɚɰɢʁɟ uKIM-1.0 (ng/mgUcr) ɭ ɨɞɧɨɫɭ ɧɚ ɬɢɩ ɧɟɮɪɟɤɬɨɦɢʁɟ ɢ ɪɟɡɭɥɬɚɬɢ ɬɟɫɬɢɪɚʃɚ Ⱦɟɫɤɪɢɩɬɢɜɧɢ ɩɨɞɚɰɢ ȼɪɟɞɧɨɫɬɢ uKIM-1.0 ɉɚɪɰɢʁɚɥɧɚ ɧɟɮɪɟɤɬɨɦɢʁɚ Ɋɚɞɢɤɚɥɧɚ ɧɟɮɪɟɤɬɨɦɢʁɚ N(%) 8 (100%) 32 (100%) ɉɪɨɫɟɤ (ɋȾ) 0.2 (0.12) 1.07 (2.02) Ɇɟɞɢʁɚɧɚ (ɨɩɫɟɝ) 0.148 (0.076-0.401) 0.403 (0.109-9.8) Ȼɟɡ ɩɨɞɚɬɚɤɚ - 1 (3%) Wilcoxon rank sum test with continuity correction: W= 40; p= 0.003 ɊȿɁɍɅɌȺɌɂ 81 Ʉɚɨ ɲɬɨ ɫɟ ɜɢɞɢ ɢɡ ɬɚɛɟɥɟ ɛɪ. 83., ɩɪɟɨɩɟɪɚɬɢɜɧɚ ɜɪɟɞɧɨɫɬ ɤɨɪɢɝɨɜɚɧɟ ɤɨɧɰɟɧɬɪɚɰɢʁɟ uKIM-1.0 ɭ ɝɪɭɩɢ ɩɚɰɢʁɟɧɚɬɚ ɤɨɞ ɤɨʁɢɯ ʁɟ ɫɩɪɨɜɟɞɟɧɚ ɪɚɞɢɤɚɥɧɚ ɧɟɮɪɟɤɬɨɦɢʁɚ ɫɬɚɬɢɫɬɢɱɤɢ ʁɟ ɡɧɚɱɚʁɧɨ ɜɢɲɚ (p=0.003) ɭ ɨɞɧɨɫɭ ɧɚ ʃɟɝɨɜɭ ɤɨɧɰɟɧɬɪɚɰɢʁɭ ɭ ɝɪɭɩɢ ɩɚɰɢʁɟɧɚɬɚ ɫɚ ɩɚɪɰɢʁɚɥɧɨɦ ɧɟɮɪɟɤɬɨɦɢʁɨɦ. ɍ ɢɫɬɪɚɠɢɜɚʃɭ ʁɟ ɫɩɪɨɜɟɞɟɧɨ ɢɫɩɢɬɢɜɚʃɟ ɜɪɟɞɧɨɫɬɢ uKIM-1 ɧɚ ɩɪɜɨʁ ɩɨɫɬɨɩɟɪɚɬɢɜɧɨʁ ɤɨɧɬɪɨɥɢ, ɨɡɧɚɱɟɧɨ ɤɚɨ uKIM-1.1, ɤɚɨ ɢ ɧɚ ɞɪɭɝɨʁ ɩɨɫɬɨɩɟɪɚɬɢɜɧɨʁ ɤɨɧɬɪɨɥɢ ɢ ɨɡɧɚɱɟɧɨ ɤɚɨ uKIM-1.2. Ʉɨɧɰɟɧɬɪɚɰɢʁɟ uKIM-1 ɫɭ ɢɫɤɚɡɚɧɟ ɭ ɚɩɫɨɥɭɬɧɢɦ ɢ ɤɨɪɢɝɨɜɚɧɢɦ ɜɪɟɞɧɨɫɬɢɦɚ. ɍ ɬɚɛɟɥɢ ɛɪ. 84. ɧɚɜɟɞɟɧɢ ɫɭ ɪɟɡɭɥɬɚɬɢ ɬɟɫɬɢɪɚʃɚ ɜɪɟɞɧɨɫɬɢ ɚɩɫɨɥɭɬɧɟ ɤɨɧɰɟɧɬɪɚɰɢʁɟ uKIM-1 ɧɚ ɩɪɜɨʁ ɩɨɫɬɨɩɟɪɚɬɢɜɧɨʁ ɤɨɧɬɪɨɥɢ, uKIM-1.1 (ng/ml) ɢ ɬɢɩɚ ɧɟɮɪɟɤɬɨɦɢʁɟ. Ɍɚɛɟɥɚ ɛɪ. 84. Ⱦɟɫɤɪɢɩɬɢɜɧɢ ɩɨɞɚɰɢ ɤɨɧɰɟɧɬɪɚɰɢʁɟ uKIM-1.1 (nР/ml) ɭ ɨɞɧɨɫɭ ɧɚ ɬɢɩ ɧɟɮɪɟɤɬɨɦɢʁɟ ɢ ɪɟɡɭɥɬɚɬɢ ɬɟɫɬɢɪɚʃɚ Ⱦɟɫɤɪɢɩɬɢɜɧɢ ɩɨɞɚɰɢ ȼɪɟɞɧɨɫɬɢ uKIM-1.1 ɉɚɪɰɢʁɚɥɧɚ ɧɟɮɪɟɤɬɨɦɢʁɚ Ɋɚɞɢɤɚɥɧɚ ɧɟɮɪɟɤɬɨɦɢʁɚ N(%) 8 (100%) 32 (100%) ɉɪɨɫɟɤ (ɋȾ) 0.41 (0.31) 0.26 (0.24) Ɇɟɞɢʁɚɧɚ (ɨɩɫɟɝ) 0.239 (0.118-0.893) 0.143 (0-0.939) Ȼɟɡ ɩɨɞɚɬɚɤɚ - 1 (3%) Wilcoxon rank sum test with continuity correction: W= 137.5; p= 0.1557 Ʉɚɨ ɲɬɨ ɫɟ ɜɢɞɢ ɢɡ ɬɚɛɟɥɟ ɛɪ. 84., ɚɩɫɨɥɭɬɧɚ ɤɨɧɰɟɧɬɪɚɰɢʁɚ uKIM-1 ɧɚ ɩɪɜɨʁ ɩɨɫɬɨɩɟɪɚɬɢɜɧɨʁ ɤɨɧɬɪɨɥɢ ɜɢɲɚ ʁɟ ɭ ɝɪɭɩɢ ɩɚɰɢʁɟɧɚɬɚ ɤɨɞ ɤɨʁɢɯ ʁɟ ɫɩɪɨɜɟɞɟɧɚ ɩɚɪɰɢʁɚɥɧɚ ɧɟɮɪɟɤɬɨɦɢʁɚ ɭ ɨɞɧɨɫɭ ɧɚ ɝɪɭɩɭ ɤɨɞ ɤɨʁɢɯ ʁɟ ɫɩɪɨɜɟɞɟɧɚ ɪɚɞɢɤɚɥɧɚ ɧɟɮɪɟɤɬɨɦɢʁɚ, ɚɥɢ ɛɟɡ ɫɬɚɬɢɫɬɢɱɤɟ ɡɧɚɱɚʁɧɨɫɬɢ (p=0.156). ɍ ɬɚɛɟɥɢ ɛɪ. 85. ɧɚɜɟɞɟɧɢ ɫɭ ɞɟɫɤɪɢɩɬɢɜɧɢ ɩɨɞɚɰɢ ɢ ɪɟɡɭɥɬɚɬɢ ɬɟɫɬɢɪɚʃɚ ɜɪɟɞɧɨɫɬɢ ɤɨɪɢɝɨɜɚɧɟ ɤɨɧɰɟɧɬɪɚɰɢʁɟ uKIM-1 ɧɚ ɩɪɜɨʁ ɩɨɫɬɨɩɟɪɚɬɢɜɧɨʁ ɤɨɧɬɪɨɥɢ, uKIM-1.1 (ng/mgUcr), ɢ ɬɢɩɚ ɧɟɮɪɟɤɬɨɦɢʁɟ. Ɍɚɛɟɥɚ ɛɪ. 85. Ⱦɟɫɤɪɢɩɬɢɜɧɢ ɩɨɞɚɰɢ ɤɨɧɰɟɧɬɪɚɰɢʁɟ uKIM-1.1 (ng/mgUcr) ɭ ɨɞɧɨɫɭ ɧɚ ɬɢɩ ɧɟɮɪɟɤɬɨɦɢʁɟ ɢ ɪɟɡɭɥɬɚɬɢ ɬɟɫɬɢɪɚʃɚ Ⱦɟɫɤɪɢɩɬɢɜɧɢ ɩɨɞɚɰɢ ȼɪɟɞɧɨɫɬɢ uKIM-1.1 ɉɚɪɰɢʁɚɥɧɚ ɧɟɮɪɟɤɬɨɦɢʁɚ Ɋɚɞɢɤɚɥɧɚ ɧɟɮɪɟɤɬɨɦɢʁɚ N(%) 8 (100%) 32 (100%) ɉɪɨɫɟɤ (ɋȾ) 0.33 (0.2) 0.33 (0.23) Ɇɟɞɢʁɚɧɚ (ɨɩɫɟɝ) 0.277 (0.183-0.769) 0.279 (0.072-0.814) Ȼɟɡ ɩɨɞɚɬɚɤɚ - 1 (3%) Wilcoxon rank sum test with continuity correction: W= 108; p= 0.8104 ɊȿɁɍɅɌȺɌɂ 82 Ʉɚɨ ɲɬɨ ɫɟ ɜɢɞɢ ɢɡ ɬɚɛɟɥɟ ɛɪ. 85., ɧɟ ɩɨɫɬɨʁɢ ɫɬɚɬɢɫɬɢɱɤɢ ɡɧɚɱɚʁɧɚ ɪɚɡɥɢɤɚ ɭ ɜɪɟɞɧɨɫɬɢ ɤɨɪɢɝɨɜɧɟ ɤɨɧɰɟɧɬɪɚɰɢʁɟ uKIM-1 ɧɚ ɩɪɜɨʁ ɩɨɫɬɨɩɟɪɚɬɢɜɧɨʁ ɤɨɧɬɪɨɥɢ ɢɡɦɟђɭ ɩɚɰɢʁɟɧɚɬɚ ɫɚ ɩɚɪɰɢʁɚɥɧɨɦ ɢ ɪɚɞɢɤɚɥɧɨɦ ɧɟɮɪɟɤɬɨɦɢʁɨɦ. ɍ ɬɚɛɟɥɢ ɛɪ. 86. ɧɚɜɟɞɟɧɢ ɫɭ ɞɟɫɤɪɢɩɬɢɜɧɢ ɩɨɞɚɰɢ ɢ ɪɟɡɭɥɬɚɬɢ ɬɟɫɬɢɪɚʃɚ ɜɪɟɞɧɨɫɬɢ ɚɩɫɨɥɭɬɧɟ ɤɨɧɰɟɧɬɪɚɰɢʁɟ uKIM-1 ɧɚ ɞɪɭɝɨʁ ɩɨɫɬɨɩɟɪɚɬɢɜɧɨʁ ɤɨɧɬɪɨɥɢ, uKIM-1.2 (ng/ml), ɢ ɬɢɩɚ ɧɟɮɪɟɤɬɨɦɢʁɟ. Ɍɚɛɟɥɚ ɛɪ. 86. Ⱦɟɫɤɪɢɩɬɢɜɧɢ ɩɨɞɚɰɢ ɤɨɧɰɟɧɬɪɚɰɢʁɟ uKIM-1.2 (nР/ml) ɭ ɨɞɧɨɫɭ ɧɚ ɬɢɩ ɧɟɮɪɟɤɬɨɦɢʁɟ ɢ ɪɟɡɭɥɬɚɬɢ ɬɟɫɬɢɪɚʃɚ Ⱦɟɫɤɪɢɩɬɢɜɧɢ ɩɨɞɚɰɢ ȼɪɟɞɧɨɫɬɢ uKIM-1.2 ɉɚɪɰɢʁɚɥɧɚ ɧɟɮɪɟɤɬɨɦɢʁɚ Ɋɚɞɢɤɚɥɧɚ ɧɟɮɪɟɤɬɨɦɢʁɚ N(%) 8 (100%) 32 (100%) ɉɪɨɫɟɤ (ɋȾ) 0.16 (0.13) 0.14 (0.21) Ɇɟɞɢʁɚɧɚ (ɨɩɫɟɝ) 0.117 (0.051-0.388) 0.077 (0.039-0.98) Ȼɟɡ ɩɨɞɚɬɚɤɚ - 1 (3%) Wilcoxon rank sum test with continuity correction: W=56.5; p= 0.4122 Ʉɚɨ ɲɬɨ ɫɟ ɜɢɞɢ ɢɡ ɬɚɛɟɥɟ ɛɪ. 86., ɧɚ ɞɪɭɝɨʁ ɩɨɫɬɨɩɟɪɚɬɢɜɧɨʁ ɤɨɧɬɪɨɥɢ ɢ ɞɚʂɟ ɫɟ ɨɞɪɠɚɜɚʁɭ ɜɢɲɟ ɜɪɟɞɧɨɫɬɢ ɚɩɫɨɥɭɬɧɟ ɤɨɧɰɟɧɬɪɚɰɢʁɟ uKIM-1 ɭ ɝɪɭɩɢ ɩɚɰɢʁɟɧɚɬɚ ɫɚ ɩɚɪɰɢʁɚɥɧɨɦ ɧɟɮɪɟɤɬɨɦɢʁɨɦ ɭ ɨɞɧɨɫɭ ɧɚ ɝɪɭɩɭ ɫɚ ɪɚɞɢɤɚɥɧɨɦ ɧɟɮɪɟɤɬɨɦɢʁɨɦ, ɚɥɢ ɛɟɡ ɫɬɚɬɢɫɬɢɱɤɟ ɡɧɚɱɚʁɧɨɫɬɢ (p=0.412). ɍ ɬɚɛɟɥɢ ɛɪ. 87. ɧɚɜɟɞɟɧɢ ɫɭ ɞɟɫɤɪɢɩɬɢɜɧɢ ɩɨɞɚɰɢ ɢ ɪɟɡɭɥɬɚɬɢ ɬɟɫɬɢɪɚʃɚ ɜɪɟɞɧɨɫɬɢ ɤɨɪɢɝɨɜɚɧɟ ɤɨɧɰɟɧɬɪɚɰɢʁɟ uKIM-1 ɧɚ ɞɪɭɝɨʁ ɩɨɫɬɨɩɟɪɚɬɢɜɧɨʁ ɤɨɧɬɪɨɥɢ, uKIM-1.2 (ng/mgUcr), ɢ ɬɢɩɚ ɧɟɮɪɟɤɬɨɦɢʁɟ. Ɍɚɛɟɥɚ ɛɪ. 87. Ⱦɟɫɤɪɢɩɬɢɜɧɢ ɩɨɞɚɰɢ ɤɨɧɰɟɧɬɪɚɰɢʁɟ uKIM-1.2 (ng/mgUcr) ɭ ɨɞɧɨɫɭ ɧɚ ɬɢɩ ɧɟɮɪɟɤɬɨɦɢʁɟ ɢ ɪɟɡɭɥɬɚɬɢ ɬɟɫɬɢɪɚʃɚ Ⱦɟɫɤɪɢɩɬɢɜɧɢ ɩɨɞɚɰɢ ȼɪɟɞɧɨɫɬɢ uKIM-1.2 ɉɚɪɰɢʁɚɥɧɚ ɧɟɮɪɟɤɬɨɦɢʁɚ Ɋɚɞɢɤɚɥɧɚ ɧɟɮɪɟɤɬɨɦɢʁɚ N(%) 8 (100%) 32 (100%) ɉɪɨɫɟɤ (ɋȾ) 0.22 (0.14) 0.16 (0.08) Ɇɟɞɢʁɚɧɚ (ɨɩɫɟɝ) 0.167 (0.098-0.456) 0.145 (0.05-0.37) Ȼɟɡ ɩɨɞɚɬɚɤɚ - 1 (3%) Wilcoxon rank sum test with continuity correction: W=58; p= 0.245 ɂɡ ɬɚɛɟɥɟ ɛɪ. 87. ɫɟ ɜɢɞɢ ɞɚ ɫɟ ɢ ɞɚʂɟ ɨɞɪɠɚɜɚʁɭ ɜɢɲɟ ɜɪɟɞɧɨɫɬɢ ɤɨɪɢɝɨɜɚɧɟ ɤɨɧɰɟɧɬɪɚɰɢʁɟ uKIM-1 ɭ ɝɪɭɩɢ ɩɚɰɢʁɟɧɚɬɚ ɫɚ ɩɚɪɰɢʁɚɥɧɨɦ ɧɟɮɪɟɤɬɨɦɢʁɨɦ ɭ ɨɞɧɨɫɭ ɧɚ ɝɪɭɩɭ ɫɚ ɪɚɞɢɤɚɥɧɨɦ ɧɟɮɪɟɤɬɨɦɢʁɨɦ, ɚɥɢ ɛɟɡ ɫɬɚɬɢɫɬɢɱɤɟ ɡɧɚɱɚʁɧɨɫɬɢ (p=0.245). ɊȿɁɍɅɌȺɌɂ 83 4.5.2. ɂɫɩɢɬɢɜɚʃɟ ɩɨɜɟɡɚɧɨɫɬɢ uAQP-1 ɢ ɜɪɫɬɟ ɨɩɟɪɚɬɢɜɧɨɝ ɥɟɱɟʃɚ Ɉɞ ɢɧɬɟɪɟɫɚ ɡɚ ɢɫɬɪɚɠɢɜɚʃɟ ɛɢɥɨ ʁɟ ɢɫɩɢɬɢɜɚʃɟ ɩɨɜɟɡɚɧɨɫɬɢ ɩɪɟɨɩɟɪɚɬɢɜɧɟ ɜɪɟɞɧɨɫɬɢ uAQP-1, ɨɡɧɚɱɟɧɨ ɤɚɨ uAQP-1.0, ɢ ɬɢɩɚ ɧɟɮɪɟɤɬɨɦɢʁɟ. ɍ ɬɚɛɟɥɢ ɛɪ. 88. ɧɚɜɟɞɟɧɢ ɫɭ ɞɟɫɤɪɢɩɬɢɜɧɢ ɩɨɞɚɰɢ ɨ ɜɪɟɞɧɨɫɬɢ ɚɩɫɨɥɭɬɧɟ ɤɨɧɰɟɧɬɪɚɰɢʁɟ uAQP-1.0(ng/ml) ɢ ɬɢɩɚ ɧɟɮɪɟɤɬɨɦɢʁɟ. Ɍɚɛɟɥɚ ɛɪ. 88. Ⱦɟɫɤɪɢɩɬɢɜɧɢ ɩɨɞɚɰɢ ɤɨɧɰɟɧɬɪɚɰɢʁɟ uAQP-1.0 (nР/ml) ɭ ɨɞɧɨɫɭ ɧɚ ɬɢɩ ɧɟɮɪɟɤɬɨɦɢʁɟ ɢ ɪɟɡɭɥɬɚɬɢ ɬɟɫɬɢɪɚʃɚ Ⱦɟɫɤɪɢɩɬɢɜɧɢ ɩɨɞɚɰɢ ȼɪɟɞɧɨɫɬɢ uAQP-1.0 ɉɚɪɰɢʁɚɥɧɚ ɧɟɮɪɟɤɬɨɦɢʁɚ Ɋɚɞɢɤɚɥɧɚ ɧɟɮɪɟɤɬɨɦɢʁɚ N(%) 8 (100%) 31 (100%) ɉɪɨɫɟɤ (ɋȾ) 0.09 (0.01) 0.1 (0.05) Ɇɟɞɢʁɚɧɚ (ɨɩɫɟɝ) 0.083 (0.073-0.103) 0.086 (0-0.287) Ȼɟɡ ɩɨɞɚɬɚɤɚ - 2 (6.06%) Wilcoxon rank sum test with continuity correction: W=104; p= 0.4968 Ʉɚɨ ɲɬɨ ɫɟ ɜɢɞɢ ɢɡ ɬɚɛɟɥɟ ɛɪ. 88., ɧɟ ɩɨɫɬɨʁɢ ɫɬɚɬɢɫɬɢɱɤɢ ɡɧɚɱɚʁɧɚ ɪɚɡɥɢɤɚ ɭ ɩɪɟɨɩɟɪɚɬɢɜɧɨʁ ɜɪɟɞɧɨɫɬɢ ɚɩɫɨɥɭɬɧɟ ɤɨɧɰɟɧɬɪɚɰɢʁɟ uAQP-1.0(ng/ml) ɢ ɬɢɩɚ ɧɟɮɪɟɤɬɨɦɢʁɟ. ɂɫɬɢ ɨɛɥɢɤ ɬɟɫɬɢɪɚʃɚ ɫɩɪɨɜɟɞɟɧ ʁɟ ɢ ɫɚ ɤɨɪɢɝɨɜɚɧɨɦ ɤɨɧɰɟɧɬɪɚɰɢʁɨɦ uAQP-1.0 (ng/mgUcr), ɚ ɪɟɡɭɥɬɚɬɢ ɫɭ ɩɪɢɤɚɡɚɧɢ ɭ ɬɚɛɟɥɢ ɛɪ. 89. Ɍɚɛɟɥɚ ɛɪ. 89. Ⱦɟɫɤɪɢɩɬɢɜɧɢ ɩɨɞɚɰɢ ɤɨɧɰɟɧɬɪɚɰɢʁɟ uAQP-1.0(ng/mgUcr) ɭ ɨɞɧɨɫɭ ɧɚ ɬɢɩ ɧɟɮɪɟɤɬɨɦɢʁɟ ɢ ɪɟɡɭɥɬɚɬɢ ɬɟɫɬɢɪɚʃɚ Ⱦɟɫɤɪɢɩɬɢɜɧɢ ɩɨɞɚɰɢ ȼɪɟɞɧɨɫɬɢ uAQP-1.0 ɉɚɪɰɢʁɚɥɧɚ ɧɟɮɪɟɤɬɨɦɢʁɚ Ɋɚɞɢɤɚɥɧɚ ɧɟɮɪɟɤɬɨɦɢʁɚ N(%) 8 (100%) 31 (100%) ɉɪɨɫɟɤ (ɋȾ) 0.13 (0.14) 0.1 (0.08) Ɇɟɞɢʁɚɧɚ (ɨɩɫɟɝ) 0.080 (0.023-0.412) 0.079 (0-0.315) Ȼɟɡ ɩɨɞɚɬɚɤɚ - 2 (6.06%) Wilcoxon rank sum test with continuity correction: W=119; p= 0.8756 Ʉɨ ɲɬɨ ɫɟ ɢɡ ɬɚɛɟɥɟ ɛɪ. 89. ɜɢɞɢ, ɬɟɫɬɢɪɚʃɟɦ ɩɪɟɨɩɟɪɚɬɢɜɧɟ ɤɨɪɢɝɨɜɚɧɟ ɤɨɧɰɟɧɬɪɚɰɢʁɟ uAQP-1.0(ng/mgUcr) ɧɢʁɟ ɞɨɛɢʁɟɧɚ ɫɬɚɬɢɫɬɢɱɤɢ ɡɧɚɱɚʁɧɚ ɪɚɡɥɢɤɚ ɭ ɜɪɟɞɧɨɫɬɢɦɚ ɢɡɦɟђɭ ɩɚɰɢʁɟɧɚɬɚ ɫɚ ɩɚɪɰɢʁɚɥɧɨɦ ɢ ɪɚɞɢɤɚɥɧɨɦ ɧɟɮɪɟɤɬɨɦɢʁɨɦ. ɍ ɢɫɬɪɚɠɢɜɚʃɭ ʁɟ ɫɩɪɨɜɟɞɟɧɨ ɢɫɩɢɬɢɜɚʃɟ ɜɪɟɞɧɨɫɬɢ uAQP-1 ɧɚ ɩɪɜɨʁ ɩɨɫɬɨɩɟɪɚɬɢɜɧɨʁ ɤɨɧɬɪɨɥɢ, ɨɡɧɚɱɟɧɨ ɤɚɨ uAQP-1.1, ɤɚɨ ɢ ɧɚ ɞɪɭɝɨʁ ɩɨɫɬɨɩɟɪɚɬɢɜɧɨʁ ɤɨɧɬɪɨɥɢ ɢ ɨɡɧɚɱɟɧɨ ɤɚɨ uAQP-1.2. Ʉɨɧɰɟɧɬɪɚɰɢʁɟ uAQP-1 ɫɭ ɢɫɤɚɡɚɧɟ ɭ ɚɩɫɨɥɭɬɧɢɦ ɢ ɤɨɪɢɝɨɜɚɧɢɦ ɜɪɟɞɧɨɫɬɢɦɚ. ɊȿɁɍɅɌȺɌɂ 84 ɍ ɬɚɛɟɥɢ ɛɪ. 90. ɧɚɜɟɞɟɧɢ ɫɭ ɪɟɡɭɥɬɚɬɢ ɬɟɫɬɢɪɚʃɚ ɜɪɟɞɧɨɫɬɢ ɚɩɫɨɥɭɬɧɟ ɤɨɧɰɟɧɬɪɚɰɢʁɟ uAQP-1 ɧɚ ɩɪɜɨʁ ɩɨɫɬɨɩɟɪɚɬɢɜɧɨʁ ɤɨɧɬɪɨɥɢ, uAQP-1.1 (ng/ml), ɢ ɬɢɩɚ ɧɟɮɪɟɤɬɨɦɢʁɟ. Ɍɚɛɟɥɚ ɛɪ. 90. Ⱦɟɫɤɪɢɩɬɢɜɧɢ ɩɨɞɚɰɢ ɤɨɧɰɟɧɬɪɚɰɢʁɟ uAQP-1.1(nР/ml) ɭ ɨɞɧɨɫɭ ɧɚ ɬɢɩ ɧɟɮɪɟɤɬɨɦɢʁɟ ɢ ɪɟɡɭɥɬɚɬɢ ɬɟɫɬɢɪɚʃɚ Ⱦɟɫɤɪɢɩɬɢɜɧɢ ɩɨɞɚɰɢ ȼɪɟɞɧɨɫɬɢ uAQP-1.1 ɉɚɪɰɢʁɚɥɧɚ ɧɟɮɪɟɤɬɨɦɢʁɚ Ɋɚɞɢɤɚɥɧɚ ɧɟɮɪɟɤɬɨɦɢʁɚ N(%) 7 (100%) 30 (100%) ɉɪɨɫɟɤ (ɋȾ) 0.08 (0.04) 0.1 (0.02) Ɇɟɞɢʁɚɧɚ (ɨɩɫɟɝ) 0.089 (0-0.109) 0.091 (0.067-0.149) Ȼɟɡ ɩɨɞɚɬɚɤɚ 1 (12.5%) 3 (9.09%) Wilcoxon rank sum test with continuity correction: W=84; p= 0.4261 Ʉɚɨ ɲɬɨ ɫɟ ɜɢɞɢ ɢɡ ɬɚɛɟɥɟ ɛɪ. 90., ɧɟ ɩɨɫɬɨʁɢ ɫɬɚɬɢɫɬɢɱɤɢ ɡɧɚɱɚʁɧɚ ɪɚɡɥɢɤɚ ɭ ɚɩɫɨɥɭɬɧɢɦ ɜɪɟɞɧɨɫɬɢɦɚ uAQP-1 ɧɚ ɩɪɜɨʁ ɩɨɫɬɨɩɟɪɚɬɢɜɧɨʁ ɤɨɧɬɪɨɥɢɢ ɬɢɩɚ ɧɟɮɪɟɤɬɨɦɢʁɟ. ɍ ɬɚɛɟɥɢ ɛɪ. 91. ɧɚɜɟɞɟɧɢ ɫɭ ɪɟɡɭɥɬɚɬɢ ɬɟɫɬɢɪɚʃɚ ɜɪɟɞɧɨɫɬɢ ɤɨɪɢɝɨɜɚɧɟ ɤɨɧɰɟɧɬɪɚɰɢʁɟ uAQP-1ɧɚ ɩɪɜɨʁ ɩɨɫɬɨɩɟɪɚɬɢɜɧɨʁ ɤɨɧɬɪɨɥɢ, uAQP-1.1 (ng/mgUcr)ɢ ɬɢɩɚ ɧɟɮɪɟɤɬɨɦɢʁɟ. Ɍɚɛɟɥɚ ɛɪ. 91. Ⱦɟɫɤɪɢɩɬɢɜɧɢ ɩɨɞɚɰɢ ɤɨɧɰɟɧɬɪɚɰɢʁɟ uAQP-1.1 (ng/mgUcr) ɭ ɨɞɧɨɫɭ ɧɚ ɬɢɩ ɧɟɮɪɟɤɬɨɦɢʁɟ ɢ ɪɟɡɭɥɬɚɬɢ ɬɟɫɬɢɪɚʃɚ Ⱦɟɫɤɪɢɩɬɢɜɧɢ ɩɨɞɚɰɢ ȼɪɟɞɧɨɫɬɢ uAQP-1.1 ɉɚɪɰɢʁɚɥɧɚ ɧɟɮɪɟɤɬɨɦɢʁɚ Ɋɚɞɢɤɚɥɧɚ ɧɟɮɪɟɤɬɨɦɢʁɚ N(%) 7 (100%) 29 (100%) ɉɪɨɫɟɤ (ɋȾ) 0.07 (0.05) 0.17 (0.03) Ɇɟɞɢʁɚɧɚ (ɨɩɫɟɝ) 0.074 (0-0.129) 0.106 (0.05-0.925) Ȼɟɡ ɩɨɞɚɬɚɤɚ 1 (12.5%) 4 (12.12%) Wilcoxon rank sum test with continuity correction: W=58; p= 0.0856 Ʉɚɨ ɲɬɨ ɫɟ ɜɢɞɢ ɢɡ ɬɚɛɟɥɟ ɛɪ. 91., ɜɪɟɞɧɨɫɬɢ ɤɨɪɢɝɨɜɚɧɟ ɤɨɧɰɟɧɬɪɚɰɢʁɟ uAQP-1 ɧɚ ɩɪɜɨʁ ɩɨɫɬɨɩɟɪɚɬɢɜɧɨʁ ɤɨɧɬɪɨɥɢ ɫɭ ɜɢɲɟ ɭ ɝɪɭɩɢ ɫɚ ɪɚɞɢɤɚɥɧɨɦ ɧɟɮɪɟɤɬɨɦɢʁɟɦ ɚɥɢ ɛɟɡ ɫɬɚɬɢɫɬɢɱɤɟ ɡɧɚɱɚʁɧɨɫɬɢ ɭ ɨɞɧɨɫɭ ɧɚ ɝɪɭɩɭ ɩɚɰɢʁɟɧɚɬɚ ɫɚ ɩɚɪɰɢʁɚɥɧɨɦ ɧɟɮɪɟɤɬɨɦɢʁɨɦ. ɍ ɬɚɛɟɥɢ ɛɪ. 92. ɧɚɜɟɞɟɧɢ ɫɭ ɪɟɡɭɥɬɚɬɢ ɬɟɫɬɢɪɚʃɚ ɜɪɟɞɧɨɫɬɢ ɚɩɫɨɥɭɬɧɟ ɤɨɧɰɟɧɬɪɚɰɢʁɟ uAQP-1 ɧɚ ɞɪɭɝɨʁ ɩɨɫɬɨɩɟɪɚɬɢɜɧɨʁ ɤɨɧɬɪɨɥɢ, uAQP-1.2 (ng/ml)ɢ ɬɢɩɚ ɧɟɮɪɟɤɬɨɦɢʁɟ. ɊȿɁɍɅɌȺɌɂ 85 Ɍɚɛɟɥɚ ɛɪ. 92. Ⱦɟɫɤɪɢɩɬɢɜɧɢ ɩɨɞɚɰɢ ɤɨɧɰɟɧɬɪɚɰɢʁɟ uAQP-1.2(nР/ml) ɭ ɨɞɧɨɫɭ ɧɚ ɬɢɩ ɧɟɮɪɟɤɬɨɦɢʁɟ ɢ ɪɟɡɭɥɬɚɬɢ ɬɟɫɬɢɪɚʃɚ Ⱦɟɫɤɪɢɩɬɢɜɧɢ ɩɨɞɚɰɢ ȼɪɟɞɧɨɫɬɢ uAQP-1.2 ɉɚɪɰɢʁɚɥɧɚ ɧɟɮɪɟɤɬɨɦɢʁɚ Ɋɚɞɢɤɚɥɧɚ ɧɟɮɪɟɤɬɨɦɢʁɚ N(%) 5 (100%) 18 (100%) ɉɪɨɫɟɤ (ɋȾ) 0.09 (0.01) 0.08 (0.04) Ɇɟɞɢʁɚɧɚ (ɨɩɫɟɝ) 0.086 (0.078-0.093) 0.083 (0-0.211) Ȼɟɡ ɩɨɞɚɬɚɤɚ 3 (37.5%) 15 (45.45%) Wilcoxon rank sum test with continuity correction: W=46; p= 0.9702 Ʉɚɨ ɲɬɨ ɫɟ ɜɢɞɢ ɢɡ ɬɚɛɟɥɟ ɛɪ. 92. ɧɟ ɩɨɫɬɨʁɢ ɫɬɚɬɢɫɬɢɱɤɢ ɡɧɚɱɚʁɧɚ ɪɚɡɥɢɤɚ ɭ ɚɩɫɨɥɭɬɧɢɦ ɜɪɟɞɧɨɫɬɢɦɚ uAQP-1 ɧɚ ɞɪɭɝɨʁ ɩɨɫɬɨɩɟɪɚɬɢɜɧɨʁ ɤɨɧɬɪɨɥɢ ɢ ɬɢɩɚ ɧɟɮɪɟɤɬɨɦɢʁɟ. ɂɫɬɢ ɨɛɥɢɤ ɬɟɫɬɢɪɚʃɚ ɫɩɪɨɜɟɞɟɧ ʁɟ ɢ ɡɚ ɜɪɟɞɧɨɫɬ ɤɨɪɢɝɨɜɚɧɟ ɤɨɧɰɟɧɬɪɚɰɢʁɟ uAQP-1 ɧɚ ɞɪɭɝɨʁ ɩɨɫɬɨɩɟɪɚɬɢɜɧɨʁ ɤɨɧɬɪɨɥɢ, uAQP-1.2 (ng/mgUcr) ɢ ɬɢɩɚ ɧɟɮɪɟɤɬɨɦɢʁɟ. Ⱦɟɫɤɪɢɩɬɢɜɧɢ ɩɨɞɚɰɢ ɢ ɪɟɡɭɥɬɚɬɢ ɬɟɫɬɢɪɚʃɚ ɩɪɢɤɚɡɚɧɢ ɫɭ ɭ ɬɚɛɟɥɢ ɛɪ. 93. Ɍɚɛɟɥɚ ɛɪ. 93. Ⱦɟɫɤɪɢɩɬɢɜɧɢ ɩɨɞɚɰɢ ɤɨɧɰɟɧɬɪɚɰɢʁɟ uAQP-1.2(ng/mgUcr) ɭ ɨɞɧɨɫɭ ɧɚ ɬɢɩ ɧɟɮɪɟɤɬɨɦɢʁɟ ɢ ɪɟɡɭɥɬɚɬɢ ɬɟɫɬɢɪɚʃɚ Ⱦɟɫɤɪɢɩɬɢɜɧɢ ɩɨɞɚɰɢ ȼɪɟɞɧɨɫɬɢ uAQP-1.2 ɉɚɪɰɢʁɚɥɧɚ ɧɟɮɪɟɤɬɨɦɢʁɚ Ɋɚɞɢɤɚɥɧɚ ɧɟɮɪɟɤɬɨɦɢʁɚ N(%) 5 (100%) 18 (100%) ɉɪɨɫɟɤ (ɋȾ) 0.16 (0.1) 0.21 (0.22) Ɇɟɞɢʁɚɧɚ (ɨɩɫɟɝ) 0.123 (0.061-0.31) 0.166 (0-0.790) Ȼɟɡ ɩɨɞɚɬɚɤɚ 3 (37.5%) 15 (45.45%) Wilcoxon rank sum test with continuity correction: W=41; p= 0.7941 ɂɡ ɬɚɛɟɥɟ ɛɪ. 93. ɫɟ ɜɢɞɢ ɞɚ ɫɟ ɧɚ ɞɪɭɝɨʁ ɩɨɫɬɨɩɟɪɚɬɢɜɧɨʁ ɤɨɧɬɪɨɥɢ ɢ ɞɚʂɟ ɨɞɪɠɚɜɚ ɩɨɜɢɲɟɧɚ ɜɪɟɞɧɨɫɬ ɤɨɪɢɝɨɜɚɧɟ ɤɨɧɰɟɧɬɪɚɰɢʁɟ uAQP-1 ɭ ɝɪɭɩɢ ɫɚ ɪɚɞɢɤɚɥɧɨɦ ɧɟɮɪɟɤɬɨɦɢʁɨɦ ɭ ɨɞɧɨɫɭ ɧɚ ɝɪɭɩɭ ɫɚ ɩɚɪɰɢʁɚɥɧɨɦ ɚɥɢ ɛɟɡ ɫɬɚɬɢɫɬɢɱɤɟ ɡɧɚɱɚʁɧɨɫɬɢ. 4.6. ɂɫɩɢɬɢɜɚʃɟ ɩɨɜɟɡɚɧɨɫɬɢ ɬɭɦɨɪɫɤɟ ɟɤɫɩɪɟɫɢʁɟ KIM-1 ɫɚ ɤɨɧɰɟɧɬɪɚɰɢʁɨɦ uKIM-1 ɢ ɩɚɬɨɯɢɫɬɨɥɨɲɤɢɦ ɤɚɪɚɤɬɟɪɢɫɬɢɤɚɦɚ ɬɭɦɨɪɚ ɭ ɝɪɭɩɢ ɨɛɨɥɟɥɢɯ 4.6.1. ɂɫɩɢɬɢɜɚʃɟ ɩɨɜɟɡɚɧɨɫɬɢ ɟɤɫɩɪɟɫɢʁɟ KIM-1 ɭ ɬɭɦɨɪɫɤɨɦ ɬɤɢɜɭ ɫɚ ɤɨɧɰɟɧɬɪɚɰɢʁɨɦ uKIM-1 ɩɪɟ ɨɩɟɪɚɰɢʁɟ ɍ ɢɫɬɪɚɠɢɜɚʃɭ ʁɟ ɫɩɪɨɜɟɞɟɧɨ ɢɫɩɢɬɢɜɚʃɟ ɜɪɟɞɧɨɫɬɢ ɚɩɫɨɥɭɬɧɟ ɤɨɧɰɟɧɬɪɚɰɢʁɟ uKIM- 1(ng/ml)ɩɪɟ ɨɩɟɪɚɰɢʁɟɢ ɧɢɜɨɚ ɬɭɦɨɪɫɤɟ ɟɤɫɩɪɟɫɢʁɟ KIM-1. Ⱦɟɫɤɪɢɩɬɢɜɧɢ ɩɨɞɚɰɢ ɢ ɪɟɡɭɥɬɚɬɢ ɬɟɫɬɢɪɚʃɚ ɫɭ ɩɪɢɤɚɡɚɧɢ ɭ ɬɚɛɟɥɢ ɛɪ. 94. ɊȿɁɍɅɌȺɌɂ 86 Ɍɚɛɟɥɚ ɛɪ. 94. Ⱦɟɫɤɪɢɩɬɢɜɧɢ ɩɨɞɚɰɢ ɩɪɟɨɩɟɪɚɬɢɜɧɟ ɤɨɧɰɟɧɬɪɚɰɢʁɟ uKIM-1(nР/ml) ɭ ɨɞɧɨɫɭ ɧɚ ɧɢɜɨ ɬɭɦɨɪɫɤɟ ɟɤɫɩɪɟɫɢʁɟ KIM-1 ɢ ɪɟɡɭɥɬɚɬɢ ɬɟɫɬɢɪɚʃɚ Ⱦɟɫɤɪɢɩɬɢɜɧɢ ɩɨɞɚɰɢ ȼɪɟɞɧɨɫɬɢ uKIM-1(ng/ml) KIM-1 ɟɤɫɩɪɟɫɢʁɚ (10-50%) KIM-1 ɟɤɫɩɪɟɫɢʁɚ (>50%) N(%) 16 (100%) 22 (100%) ɉɪɨɫɟɤ (ɋȾ) 0.36 (0.26) 1.34 (1.69) Ɇɟɞɢʁɚɧɚ (ɨɩɫɟɝ) 0.29 (0.038-1) 0.37 (0.075-5) Ȼɟɡ ɩɨɞɚɬɚɤɚ 2 (12.5%) 3 (13.64%) Wilcoxon rank sum test with continuity correction: W=134; p= 0.219 Ʉɚɨ ɲɬɨ ɫɟ ɜɢɞɢ ɢɡ ɬɚɛɟɥɟ ɛɪ. 94.,ɩɪɟɨɩɟɪɚɬɢɜɧɚ ɜɪɟɞɧɨɫɬ ɚɩɫɨɥɭɬɧɟ ɤɨɧɰɟɧɬɪɚɰɢʁɟ uKIM- 1(ng/ml) ɭ ɝɪɭɩɢ ɬɭɦɨɪɚ ɫɚ ɟɤɫɩɪɟɫɢʁɨɦ KIM-1 ɜɟʄɨɦ ɨɞ 50% ʁɟ ɜɟʄɚ ɭ ɨɞɧɨɫɭ ɧɚ ɜɪɟɞɧɨɫɬ uKIM-1(ng/ml) ɭ ɝɪɭɩɢ ɬɭɦɨɪɚ ɫɚ KIM-1 ɟɤɫɩɪɟɫɢʁɨɦ 10-50% ɚɥɢ ɬɚ ɪɚɡɥɢɤɚ ɧɢʁɟ ɫɬɚɬɢɫɬɢɱɤɢ ɡɧɚɱɚʁɧɚ. Ⱦɟɫɤɪɢɩɬɢɜɧɢ ɩɨɞɚɰɢ ɢ ɪɟɡɭɥɬɚɬɢ ɬɟɫɬɢɪɚʃɚ ɩɪɟɨɩɟɪɚɬɢɜɧɟ ɜɪɟɞɧɨɫɬɢ ɤɨɪɢɝɨɜɚɧɟ ɤɨɧɰɟɧɬɪɚɰɢʁɟ uKIM-1(ng/mgUcr) ɢ ɧɢɜɨɚ ɬɭɦɨɪɫɤɟ ɟɤɫɩɪɟɫɢʁɟ KIM-1 ɩɪɢɤɚɡɚɧɢ ɫɭ ɭ ɬɚɛɟɥɢ ɛɪ. 95. Ɍɚɛɟɥɚ ɛɪ. 95. Ⱦɟɫɤɪɢɩɬɢɜɧɢ ɩɨɞɚɰɢ ɩɪɟɨɩɟɪɚɬɢɜɧɟ ɤɨɧɰɟɧɬɪɚɰɢʁɟ uKIM-1(ng/mgUcr) ɭ ɨɞɧɨɫɭ ɧɚ ɧɢɜɨ ɬɭɦɨɪɫɤɟ ɟɤɫɩɪɟɫɢʁɟ KIM-1 ɢ ɪɟɡɭɥɬɚɬɢ ɬɟɫɬɢɪɚʃɚ Ⱦɟɫɤɪɢɩɬɢɜɧɢ ɩɨɞɚɰɢ ȼɪɟɞɧɨɫɬɢ uKIM-1(ng/mgUcr) KIM-1 ɟɤɫɩɪɟɫɢʁɚ (10-50%) KIM-1 ɟɤɫɩɪɟɫɢʁɚ (>50%) N(%) 16 (100%) 22 (100%) ɉɪɨɫɟɤ (ɋȾ) 0.28 (0.12) 1.28 (2.37) Ɇɟɞɢʁɚɧɚ (ɨɩɫɟɝ) 0.252 (0.113-0.454) 0.422 (0.076-9.8) Ȼɟɡ ɩɨɞɚɬɚɤɚ 2 (12.5%) 3 (13.64%) Wilcoxon rank sum test with continuity correction: W=106.5; p= 0.041 Ʉɚɨ ɲɬɨ ɫɟ ɜɢɞɢ ɢɡ ɬɚɛɟɥɟ ɛɪ. 95., ɤɨɪɢɝɨɜɚɧɚ ɜɪɟɞɧɨɫɬ ɩɪɟɨɩɟɪɚɬɢɜɧɟ ɤɨɧɰɟɧɬɪɚɰɢʁɚ uKIM-1(ng/mgUcr) ɭ ɝɪɭɩɢ ɬɭɦɨɪɚ ɫɚ ɟɤɫɩɪɟɫɢʁɨɦ KIM-1 ɜɟʄɨɦ ɨɞ 50%,ɫɬɚɬɢɫɬɢɱɤɢ ʁɟ ɡɧɚɱɚʁɧɨ ɜɢɲɚ (p=0.041) ɭ ɨɞɧɨɫɭ ɧɚ ɜɪɟɞɧɨɫɬ uKIM-1(ng/mgUcr) ɭ ɝɪɭɩɢ ɬɭɦɨɪɚ ɫɚ KIM-1 ɟɤɫɩɪɟɫɢʁɨɦ 10-50%. 4.6.2. ɂɫɩɢɬɢɜɚʃɟ ɩɨɜɟɡɚɧɨɫɬɢ ɬɭɦɨɪɫɤɟ ɟɤɫɩɪɟɫɢʁɟ KIM-1 ɫɚ ɩɚɬɨɯɢɫɬɨɥɨɲɤɢɦ ɤɚɪɚɤɬɟɪɢɫɬɢɤɚɦɚ ɬɭɦɨɪɚ Ɉɞ ɢɧɬɟɪɟɫɚ ɡɚ ɢɫɬɪɚɠɢɜɚʃɟ ɛɢɥɨ ʁɟ ɞɚ ɫɟ ɢɫɩɢɬɚ ɩɨɜɟɡɚɧɨɫɬ ɢɡɦɟђɭ ɜɟɥɢɱɢɧɟ ɬɭɦɨɪɚ ɢ ɬɭɦɨɪɫɤɟ KIM-1 ɟɤɫɩɪɟɫɢʁɟ. Ⱦɟɫɤɪɢɩɬɢɜɧɢ ɩɨɞɚɰɢ ɢ ɪɟɡɭɥɬɚɬɢ ɬɟɫɬɢɪɚʃɚ ɩɪɢɤɚɡɚɧɢ ɫɭ ɭ ɬɚɛɟɥɢ ɛɪ. 96. ɊȿɁɍɅɌȺɌɂ 87 Ɍɚɛɟɥɚ ɛɪ. 96. Ⱦɟɫɤɪɢɩɬɢɜɧɢ ɩɨɞɚɰɢ ɜɟɥɢɱɢɧɟ ɬɭɦɨɪɚ (cm) ɢ ɟɤɫɩɪɟɫɢʁɟ KIM-1 ɭ ɬɭɦɨɪɫɤɨɦ ɬɤɢɜɭ ɢ ɢ ɪɟɡɭɥɬɚɬɢ ɬɟɫɬɢɪɚʃɚ Ⱦɟɫɤɪɢɩɬɢɜɧɢ ɩɨɞɚɰɢ ɜɟɥɢɱɢɧɟ ɬɭɦɨɪɚ (cm) KIM-1 ɬɭɦɨɪɫɤɚ ɟɤɫɩɪɟɫɢʁɚ 10-50% (2+) >50% (3+) N(%) 16 (100%) 23 (100%) ɉɪɨɫɟɤ (ɋȾ) 4.58 (2.61) 5.82 (3.19) Ɇɟɞɢʁɚɧɚ (ɨɩɫɟɝ) 3.85 (2-12) 4.5 (2-13) Ȼɟɡ ɩɨɞɚɬɚɤɚ 1(6.25%) 1(4.35%) Wilcoxon rank sum test with continuity correction: W=135; p= 0.165 Ʉɚɨ ɲɬɨ ɫɟ ɜɢɞɢ ɢɡ ɬɚɛɟɥɟ ɛɪ. 96.,ɬɭɦɨɪɢ ɫɚ KIM-1 ɟɤɫɩɪɟɫɢʁɨɦ >50% (3+) ɫɭ ɜɟʄɢɯ ɞɢɦɟɧɡɢʁɚ ɭ ɨɞɧɨɫɭ ɧɚ ɬɭɦɨɪɟ ɫɚ KIM-1 ɬɭɦɨɪɫɤɨɦ ɟɤɫɩɪɟɫɢʁɨɦ 10-50% (2+), ɚɥɢ ɬɚ ɪɚɡɥɢɤɚ ɧɢʁɟ ɫɬɚɬɢɫɬɢɱɤɢ ɡɧɚɱɚʁɧɚ. ɍ ɢɫɬɪɚɠɢɜɚʃɭ ʁɟ ɫɩɪɨɜɟɞɟɧɨ ɢɫɩɢɬɢɜɚʃɟ ɤɚɬɟɝɨɪɢʁɚ KIM-1 ɬɭɦɨɪɫɤɟ ɟɤɫɩɪɟɫɢʁɟ ɭ ɨɞɧɨɫɭ ɧɚ ɤɚɬɟɝɨɪɢʁɟ ɜɟɥɢɱɢɧɟ ɬɭɦɨɪɚ ɢ ɪɟɡɭɥɬɚɬɢ ɬɟɫɬɢɪɚʃɚ ɫɭ ɩɪɢɤɚɡɚɧɢ ɭ ɬɚɛɟɥɢ ɛɪ. 97. Ɍɚɛɟɥɚ ɛɪ. 97. Ⱦɟɫɤɪɢɩɬɢɜɧɢ ɩɨɞɚɰɢ KIM-1 ɬɭɦɨɪɫɤɟ ɟɤɫɩɪɟɫɢʁɟ ɭ ɨɞɧɨɫɭ ɧɚ ɤɚɬɟɝɨɪɢʁɟ ɜɟɥɢɱɢɧɟ ɬɭɦɨɪɚ ɢ ɪɟɡɭɥɬɚɬɢ ɬɟɫɬɢɪɚʃɚ KIM-1ɬɭɦɨɪɫɤɚ ɟɤɫɩɪɟɫɢʁɚ Ʉɚɬɟɝɨɪɢʁɟ ɜɟɥɢɱɢɧɟ ɬɭɦɨɪɚ Fisher-ɨɜ Exact ɬɟɫɬ ≤4МЦ (1) N (%) 4.1-7 cm (2) N (%) >7 cm (3) N (%) 10-50% (2+) 8 (44.44%) 5 (45.45%) 3 (25%) p= 0.767 >50% (3+) 10 (55.56%) 6 (54.55%) 7 (58.33%) Ȼɟɡ ɩɨɞɚɬɚɤɚ - - 2 (16.67%) Ʉɚɨ ɲɬɨ ɫɟ ɢɡ ɬɚɛɟɥɟ ɛɪ. 97. ɜɢɞɢ, ɧɟ ɩɨɫɬɨʁɢ ɫɬɚɬɢɫɬɢɱɤɢ ɡɧɚɱɚʁɧɚ ɪɚɡɥɢɤɚ ɭ KIM-1 ɬɭɦɨɪɫɤɨʁ ɟɤɫɩɪɟɫɢʁɢ ɢɡɦɟђɭ ɤɚɬɟɝɨɪɢʁɚ ɜɟɥɢɱɢɧɟ ɬɭɦɨɪɚ, ɲɬɨ ʁɟ ɩɨɬɜɪђɟɧɨ ɞɨɞɚɬɧɢɦ ɬɟɫɬɢɪɚʃɟɦ ɢɡɦɟђɭ ɩɚɪɨɜɚ ɤɚɬɟɝɨɪɢʁɚ ɜɟɥɢɱɢɧɟ ɬɭɦɨɪɚ (ɬɚɛɟɥɚ ɛɪ. 98.). Ɍɚɛɟɥɚ ɛɪ. 98. Ɋɟɡɭɥɬɚɬɢ ɬɟɫɬɢɪɚʃɚ KIM-1 ɬɭɦɨɪɫɤɟ ɟɤɫɩɪɟɫɢʁɟ ɩɨ ɩɚɪɨɜɢɦɚ ɤɚɬɟɝɨɪɢʁɚ ɜɟɥɢɱɢɧɟ ɬɭɦɨɪɚ ɉɚɪɨɜɢ ɤɚɬɟɝɨɪɢʁɚ ɜɟɥɢɱɢɧɟ ɬɭɦɨɪɚ Fisher-ɨɜ Exact ɬɟɫɬ ɡɚ ɩɚɪɨɜɟ ≤4 cm vs 4.1-7 cm p*= 1 ≤4 cm vs >7 cm p*= 0.689 4.1-7 cm vs > 7cm p*= 0.659 *Bonferroni korekcija: 0.05/3=0.0167 ɊȿɁɍɅɌȺɌɂ 88 ɍ ɢɫɬɪɚɠɢɜɚʃɭ ʁɟ ɫɩɪɨɜɟɞɟɧɨ ɢɫɩɢɬɢɜɚʃɟ ɤɚɬɟɝɨɪɢʁɚ KIM-1 ɬɭɦɨɪɫɤɟ ɟɤɫɩɪɟɫɢʁɟ ɭ ɨɞɧɨɫɭ ɧɚ ɤɚɬɟɝɨɪɢʁɟ ɯɢɫɬɨɥɨɲɤɨɝ ɝɪɚɞɭɫɚ ɬɭɦɨɪɚ ɢ ɪɟɡɭɥɬɚɬɢ ɬɟɫɬɢɪɚʃɚ ɫɭ ɩɪɢɤɚɡɚɧɢ ɭ ɬɚɛɟɥɢ ɛɪ. 99. Ɍɚɛɟɥɚ ɛɪ. 99. Ⱦɟɫɤɪɢɩɬɢɜɧɢ ɩɨɞɚɰɢ KIM-1 ɬɭɦɨɪɫɤɟ ɟɤɫɩɪɟɫɢʁɟ ɭ ɨɞɧɨɫɭ ɧɚ ɤɚɬɟɝɨɪɢʁɟ ɯɢɫɬɨɥɨɲɤɨɝ ɝɪɚɞɭɫɚ ɬɭɦɨɪɚ ɢ ɪɟɡɭɥɬɚɬɢ ɬɟɫɬɢɪɚʃɚ KIM-1ɬɭɦɨɪɫɤɚ ɟɤɫɩɪɟɫɢʁɚ Ʉɚɬɟɝɨɪɢʁɟ ɯɢɫɬɨɥɨɲɤɨɝ ɝɪɚɞɭɫɚ ɬɭɦɨɪɚ Fisher-ɨɜ Exact ɬɟɫɬ G2 (1) N (%) G3 (2) N (%) G4 (3) N (%) 10-50% (2+) 15 (46.88%) 1 (12.5%) 0 (0%) p= 0.205 >50% (3+) 16 (50%) 6 (75%) 1 (100%) Ȼɟɡ ɩɨɞɚɬɚɤɚ 1 (3.12%) 1 (12.5%) - Ʉɚɨ ɲɬɨ ɫɟ ɢɡ ɬɚɛɟɥɟ ɛɪ. 99. ɜɢɞɢ, ɧɟ ɩɨɫɬɨʁɢ ɫɬɚɬɢɫɬɢɱɤɢ ɡɧɚɱɚʁɧɚ ɪɚɡɥɢɤɚ ɭ KIM-1 ɬɭɦɨɪɫɤɨʁ ɟɤɫɩɪɟɫɢʁɢ ɢɡɦɟђɭ ɤɚɬɟɝɨɪɢʁɚ ɯɢɫɬɨɥɨɲɤɨɝ ɝɪɚɞɭɫɚ ɬɭɦɨɪɚ. Ɍɨ ʁɟ ɩɨɬɜɪђɟɧɨ ɢ ɞɨɞɚɬɧɢɦ ɬɟɫɬɢɪɚʃɟɦ ɢɡɦɟђɭ ɩɚɪɨɜɚ ɤɚɬɟɝɨɪɢʁɚ ɝɪɚɞɭɫɚ ɬɭɦɨɪɚ (ɬɚɛɟɥɚ ɛɪ. 100.) Ɍɚɛɟɥɚ ɛɪ. 100. Ɋɟɡɭɥɬɚɬɢ ɬɟɫɬɢɪɚʃɚ KIM-1ɬɭɦɨɪɫɤɟ ɟɤɫɩɪɟɫɢʁɟ ɩɨ ɩɚɪɨɜɢɦɚ ɤɚɬɟɝɨɪɢʁɚ ɯɢɫɬɨɥɨɲɤɨɝ ɝɪɚɞɭɫɚ ɬɭɦɨɪɚ ɉɚɪɨɜɢ ɤɚɬɟɝɨɪɢʁɚ ɯɢɫɬɨɥɨɲɤɨɝ ɝɪɚɞɭɫɚ ɬɭɦɨɪɚ Fisher-ɨɜ Exact ɬɟɫɬ ɡɚ ɩɚɪɨɜɟ G2vs G3 p*= 0.203 G2 vs G4 p*= 1 G3 vs G4 p*= 1 *Bonferroni korekcija: 0.05/3=0.0167 ɍ ɬɚɛɟɥɢ ɛɪ. 101. ɧɚɜɟɞɟɧɢ ɫɭ ɪɟɡɭɥɬɚɬɢ ɬɟɫɬɢɪɚʃɚ ɤɚɬɟɝɨɪɢʁɚ KIM-1 ɬɭɦɨɪɫɤɟ ɟɤɫɩɪɟɫɢʁɟ ɭ ɨɞɧɨɫɭ ɧɚ ɤɚɬɟɝɨɪɢʁɟ ɩɚɬɨɥɨɲɤɨɝ ɫɬɚɞɢʁɭɦɚ ɬɭɦɨɪɚ. Ɍɚɛɟɥɚ ɛɪ. 101. Ⱦɟɫɤɪɢɩɬɢɜɧɢ ɩɨɞɚɰɢ KIM-1 ɬɭɦɨɪɫɤɟ ɟɤɫɩɪɟɫɢʁɟ ɭ ɨɞɧɨɫɭ ɧɚ ɤɚɬɟɝɨɪɢʁɟ ɩɚɬɨɥɨɲɤɢɯ ɫɬɚɞɢʁɭɦɚ ɬɭɦɨɪɚ ɢ ɪɟɡɭɥɬɚɬɢ ɬɟɫɬɢɪɚʃɚ KIM-1ɬɭɦɨɪɫɤɚ ɟɤɫɩɪɟɫɢʁɚ Ʉɚɬɟɝɨɪɢʁɟ ɩɚɬɨɥɨɲɤɢɯ ɫɬɚɞɢʁɭɦɚ ɬɭɦɨɪɚ Fisher-ɨɜ Exact ɬɟɫɬ 1a (1) N (%) 1b (2) N (%) 2a (3) N (%) 3a (4) N (%) 10-50% (2+) 6 (46.15%) 5 (54.55%) 1 (33.33%) 3 (21.43%) >50% (3+) 7 (53.85%) 5 (45.45%) 2 (66.67%) 9 (64.29%) p= 0.545 Ȼɟɡ ɩɨɞɚɬɚɤɚ - - - 2 (14.29%) Ʉɚɨ ɲɬɨ ɫɟ ɢɡ ɬɚɛɟɥɟ ɛɪ. 101. ɜɢɞɢ, ɧɟ ɩɨɫɬɨʁɢ ɫɬɚɬɢɫɬɢɱɤɢ ɡɧɚɱɚʁɧɚ ɪɚɡɥɢɤɚ ɭ KIM-1 ɬɭɦɨɪɫɤɨʁ ɟɤɫɩɪɟɫɢʁɢ ɢɡɦɟђɭ ɤɚɬɟɝɨɪɢʁɚ ɩɚɬɨɥɨɲɤɨɝ ɫɬɚɞɢʁɭɦɚ ɬɭɦɨɪɚ. Ⱦɨɞɚɬɧɢɦ ɬɟɫɬɢɪɚʃɟɦ ɩɚɪɨɜɚ ɤɚɬɟɝɨɪɢʁɚ ɩɚɬɨɥɨɲɤɨɝ ɫɬɚɞɢʁɭɦɚ ɬɭɦɨɪɚ ɧɢʁɟ ɩɨɤɚɡɚɧɚ ɫɬɚɬɢɫɬɢɱɤɢ ɡɧɚɱɚʁɧɚ ɪɚɡɥɢɤɚ ɭ KIM-1 ɬɭɦɨɪɫɤɨʁ ɟɤɫɩɪɟɫɢʁɢ ɢɡɦɟђɭ ɩɚɪɨɜɚ (ɬɚɛɟɥɚ ɛɪ. 102.). ɊȿɁɍɅɌȺɌɂ 89 Ɍɚɛɟɥɚ ɛɪ. 102. Ɋɟɡɭɥɬɚɬɢ ɬɟɫɬɢɪɚʃɚ KIM-1 ɬɭɦɨɪɫɤɟ ɟɤɫɩɪɟɫɢʁɟ ɩɨ ɩɚɪɨɜɢɦɚ ɤɚɬɟɝɨɪɢʁɚ ɩɚɬɨɥɨɲɤɢɯ ɫɬɚɞɢʁɭɦɚ ɬɭɦɨɪɚ ɉɚɪɨɜɢ ɤɚɬɟɝɨɪɢʁɚ ɩɚɬɨɥɨɲɤɢɯ ɫɬɚɞɢʁɭɦɚ ɬɭɦɨɪɚ Fisher-ɨɜ Exact ɬɟɫɬ ɡɚ ɩɚɪɨɜɟ 1ɚ vs 1ɛ p*= 1 1ɚ vs 2ɚ p*= 1 1ɚ vs 3ɚ p*= 0.411 1ɛ vs 2ɚ p*= 1 1ɛ vs 3ɚ p*= 0.214 2ɚ vs 3ɚ p*= 1 *BonПОrronТ ɤɨɪɟɤцɢјɚ: 0.05/6=0.0083 ɋɩɪɨɜɟɞɟɧɨ ʁɟ ɢɫɩɢɬɢɜɚʃɟ ɤɚɬɟɝɨɪɢʁɚ KIM-1 ɬɭɦɨɪɫɤɟ ɟɤɫɩɪɟɫɢʁɟ ɭ ɨɞɧɨɫɭ ɧɚ ɤɚɬɟɝɨɪɢʁɟ ɩɨɫɬɨɩɟɪɚɬɢɜɧɨɝ TNM ɫɬɚɞɢʁɭɦɚ, ɚ ɞɟɫɤɪɢɩɬɢɜɧɢ ɩɨɞɚɰɢ ɢ ɪɟɡɭɥɬɚɬɢ ɬɟɫɬɢɪɚʃɚ ɫɭ ɩɪɢɤɚɡɚɧɢ ɭ ɬɚɛɟɥɢ ɛɪ. 103. Ɍɚɛɟɥɚ ɛɪ. 103. Ⱦɟɫɤɪɢɩɬɢɜɧɢ ɩɨɞɚɰɢ KIM-1 ɬɭɦɨɪɫɤɟ ɟɤɫɩɪɟɫɢʁɟ ɭ ɨɞɧɨɫɭ ɧɚ ɤɚɬɟɝɨɪɢʁɟ ɩɨɫɬɨɩɟɪɚɬɢɜɧɨɝ TNM ɫɬɚɞɢʁɭɦɚ ɢ ɪɟɡɭɥɬɚɬɢ ɬɟɫɬɢɪɚʃɚ KIM-1ɬɭɦɨɪɫɤɚ ɟɤɫɩɪɟɫɢʁɚ Ʉɚɬɟɝɨɪɢʁɟ ɩɨɫɬɨɩɟɪɚɬɢɜɧɨɝ TNM ɫɬɚɞɢʁɭɦɚ Fisher-ɨɜ Exact ɬɟɫɬ I (1) N (%) II (2) N (%) III (3) N (%) IV (4) N (%) 10-50% (2+) 12 (52.17%) 1 (33.33%) 3 (23.08%) 1 (50%) >50% (3+) 11 (47.83%) 2 (66.67%) 9 (69.23%) 1 (50%) p= 0.375 Ȼɟɡ ɩɨɞɚɬɚɤɚ - - 1 (7.69%) - ɂɡ ɬɚɛɟɥɟ ɛɪ. 103. ɫɟ ɜɢɞɢ ɞɚ ɧɟ ɩɨɫɬɨʁɢ ɫɬɚɬɢɫɬɢɱɤɢ ɡɧɚɱɚʁɧɚ ɪɚɡɥɢɤɚ ɭ KIM-1 ɬɭɦɨɪɫɤɨʁ ɟɤɫɩɪɟɫɢʁɢ ɢɡɦɟђɭ ɤɚɬɟɝɨɪɢʁɚ ɩɨɫɬɨɩɟɪɚɬɢɜɧɨɝ TNM ɫɬɚɞɢʁɭɦɚ ɬɭɦɨɪɚ. Ⱦɨɞɚɬɧɢɦ ɬɟɫɬɢɪɚʃɟɦ ɩɚɪɨɜɚ ɤɚɬɟɝɨɪɢʁɚ ɩɨɫɬɨɩɟɪɚɬɢɜɧɨɝ TNM ɫɬɚɞɢʁɭɦɚ ɬɭɦɨɪɚ ɧɢʁɟ ɩɨɤɚɡɚɧɚ ɫɬɚɬɢɫɬɢɱɤɢ ɡɧɚɱɚʁɧɚ ɪɚɡɥɢɤɚ ɭ KIM-1 ɬɭɦɨɪɫɤɨʁ ɟɤɫɩɪɟɫɢʁɢ ɢɡɦɟђɭ ɩɚɪɨɜɚ (ɬɚɛɟɥɚ ɛɪ. 104.). Ɍɚɛɟɥɚ ɛɪ. 104. Ɋɟɡɭɥɬɚɬɢ ɬɟɫɬɢɪɚʃɚ KIM-1ɬɭɦɨɪɫɤɟ ɟɤɫɩɪɟɫɢʁɟɩɨ ɩɚɪɨɜɢɦɚ ɤɚɬɟɝɨɪɢʁɚ ɩɨɫɬɨɩɟɪɚɬɢɜɧɨɝ TNM ɫɬɚɞɢʁɭɦɚ ɉɚɪɨɜɢ ɤɚɬɟɝɨɪɢʁɚ ɩɚɬɨɥɨɲɤɢɯ ɫɬɚɞɢʁɭɦɚ ɬɭɦɨɪɚ Fisher-ɨɜ Exact ɬɟɫɬ ɡɚ ɩɚɪɨɜɟ I vs II p*= 1 I vs III p*= 0.163 I vs IV p*= 1 II vs III p*= 1 II vs IV p*= 1 III vs IV p*= 1 *BonПОrronТ ɤɨɪɟɤцɢјɚ: 0.05/6=0.0083 Ɉɞ ɢɧɬɟɪɟɫɚ ɡɚ ɢɫɬɪɚɠɢɜɚʃɟ ɛɢɥɨ ʁɟ ɢɫɩɢɬɢɜɚʃɟ ɤɚɬɟɝɨɪɢʁɚ KIM-1 ɬɭɦɨɪɫɤɟ ɟɤɫɩɪɟɫɢʁɟ ɭ ɨɞɧɨɫɭ ɧɚ ɤɚɬɟɝɨɪɢʁɟ ɬɭɦɨɪɫɤɟ ɥɢɦɮɧɨ-ɜɚɫɤɭɥɚɪɧɟ ɢɧɜɚɡɢʁɟ. Ⱦɟɫɤɪɢɩɬɢɜɧɢ ɩɨɞɚɰɢ ɢ ɪɟɡɭɥɬɚɬɢ ɬɟɫɬɢɪɚʃɚ ɩɪɢɤɚɡɚɧɢ ɫɭ ɭ ɬɚɛɟɥɢ ɛɪ. 105. ɊȿɁɍɅɌȺɌɂ 90 Ɍɚɛɟɥɚ ɛɪ. 105. Ⱦɟɫɤɪɢɩɬɢɜɧɢ ɩɨɞɚɰɢ KIM-1 ɬɭɦɨɪɫɤɟ ɟɤɫɩɪɟɫɢʁɟ ɭ ɨɞɧɨɫɭ ɧɚ ɤɚɬɟɝɨɪɢʁɟ ɬɭɦɨɪɫɤɟ ɥɢɦɮɧɨ-ɜɚɫɤɭɥɚɪɧɟ ɢɧɜɚɡɢʁɟ KIM-1ɬɭɦɨɪɫɤɚ ɟɤɫɩɪɟɫɢʁɚ Ʉɚɬɟɝɨɪɢʁɟ ɬɭɦɨɪɫɤɟ ɥɢɦɮɧɨ-ɜɚɫɤɭɥɚɪɧɟ ɢɧɜɚɡɢʁɟ Fisher-ɨɜ Exact ɬɟɫɬ L0V0 (1) N (%) L0V1 (L1V0) (2) N (%) L1V1 (3) N (%) 10-50% (2+) 5 (71.43%) 7 (53.85%) 4 (19.05%) p= 0.041 >50% (3+) 2 (28.57%) 6 (46.15%) 15 (71.43%) Ȼɟɡ ɩɨɞɚɬɚɤɚ - - 2 (4.88%) Ʉɚɨ ɲɬɨ ɫɟ ɢɡ ɬɚɛɟɥɟ ɛɪ. 105. ɜɢɞɢ, ɩɨɫɬɨʁɢ ɫɬɚɬɢɫɬɢɱɤɢ ɡɧɚɱɚʁɧɚ ɪɚɡɥɢɤɚ ɭ KIM-1 ɬɭɦɨɪɫɤɨʁ ɟɤɫɩɪɟɫɢʁɢ ɢɡɦɟђɭ ɤɚɬɟɝɨɪɢʁɚ ɬɭɦɨɪɫɤɟ ɥɢɦɮɧɨ-ɜɚɫɤɭɥɚɪɧɟ ɢɧɜɚɡɢʁɟ (p=0.041). Ⱦɨɞɚɬɧɢɦ ɬɟɫɬɢɪɚʃɟɦ ɞɨɛɢʁɟɧɢ ɫɭ ɪɟɡɭɥɬɚɬɢ ɩɪɢɤɚɡɚɧɢ ɭ ɬɚɛɟɥɢ ɛɪ. 106. Ɍɚɛɟɥɚ ɛɪ. 106. Ɋɟɡɭɥɬɚɬɢ ɬɟɫɬɢɪɚʃɚ KIM-1ɬɭɦɨɪɫɤɟ ɟɤɫɩɪɟɫɢʁɟɩɨ ɩɚɪɨɜɢɦɚ ɤɚɬɟɝɨɪɢʁɚ ɥɢɦɮɧɨ-ɜɚɫɤɭɥɚɪɧɟ ɢɧɜɚɡɢʁɟ ɉɚɪɨɜɢ ɤɚɬɟɝɨɪɢʁɚ ɯɢɫɬɨɥɨɲɤɨɝ ɝɪɚɞɭɫɚ ɬɭɦɨɪɚ Fisher-ɨɜ Exact ɬɟɫɬ ɡɚ ɩɚɪɨɜɟ L0V0 vs L0V1 (L1V0) p*= 0.642 L0V0 vs L1V1 p*= 0.028 L0V1 (L1V0) vs L1V1 p*= 0.072 *Bonferroni korekcija: 0.05/3=0.0167 Ʉɚɨ ɲɬɨ ɫɟ ɢɡ ɬɚɛɟɥɟ ɛɪ. 106. ɜɢɞɢ, ɬɟɫɬɢɪɚʃɟɦ ɩɚɪɨɜɚ ɤɚɬɟɝɨɪɢʁɚ ɥɢɦɮɧɨ-ɜɚɫɤɭɥɚɪɧɟ ɢɧɜɚɡɢʁɟ,ɧɢʁɟ ɩɨɤɚɡɚɧɚ ɫɬɚɬɢɫɬɢɱɤɢ ɡɧɚɱɚʁɧɚ ɪɚɡɥɢɤɚ ɭ KIM-1 ɬɭɦɨɪɫɤɨʁ ɟɤɫɩɪɟɫɢʁɢ ɢɡɦɟђɭ ɩɚɪɨɜɚ, ɦɚɞɚ ɫɟ ɨɧɚ ɩɪɢɛɥɢɠɚɜɚ ɫɬɚɬɢɫɬɢɱɤɨʁ ɡɧɚɱɚʁɧɨɫɬɢ ɢɡɦɟђɭ ɢɡɦɟђɭ ɝɪɭɩɟ ɛɟɡ ɢ ɝɪɭɩɟ ɫɚ ɥɢɦɮɧɨ-ɜɚɫɤɭɥɚɪɧɨɦ ɢɧɜɚɡɢʁɨɦ. 4.7. ɂɫɩɢɬɢɜɚʃɟ ɞɢʁɚɝɧɨɫɬɢɱɤɨɝ ɩɨɬɟɧɰɢʁɚɥɚ ɩɪɟɨɩɟɪɚɬɢɜɧɢɯ ɜɪɟɞɧɨɫɬɢ uKIM-1 ɢ uAQP-1ɡɚ ɤɚɪɰɢɧɨɦ ɫɜɟɬɥɢɯ ʄɟɥɢʁɚ ɛɭɛɪɟɝɚ 4.7.1. ɂɫɩɢɬɢɜɚʃɟ ɞɢʁɚɝɧɨɫɬɢɱɤɨɝ ɩɨɬɟɧɰɢʁɚɥɚ ɩɪɟɨɩɟɪɚɬɢɜɧɢɯ ɜɪɟɞɧɨɫɬɢ uKIM- 1ɡɚ ɤɚɪɰɢɧɨɦ ɫɜɟɬɥɢɯ ʄɟɥɢʁɚ ɛɭɛɪɟɝɚ Ɉɞ ɢɧɬɟɪɟɫɚ ɡɚ ɨɜɨ ɢɫɬɪɚɠɢɜɚʃɟ ɛɢɥɨ ʁɟ ɢɫɩɢɬɢɜɚʃɟ ɞɢʁɚɝɧɨɫɬɢɱɤɨɝ ɩɨɬɟɧɰɢʁɚɥɚ ɩɪɟɨɩɟɪɚɬɢɜɧɢɯ ɜɪɟɞɧɨɫɬɢ ɭɪɢɧɚɪɧɟ ɤɨɧɰɟɧɬɪɚɰɢʁɟ KIM-1 ɡɚ ɤɚɪɰɢɧɨɦ ɫɜɟɬɥɢɯ ʄɟɥɢʁɚ ɛɭɛɪɟɝɚ. Ɋɟɡɭɥɬɚɬɢ ɫɬɚɬɢɫɬɢɱɤɟ ɚɧɚɥɢɡɟ ɫɭ ɩɪɢɤɚɡɚɧɢ ɭ ɬɚɛɟɥɢ ɛɪ. 107. ɢ ɧɚ ɝɪɚɮɢɤɨɧɭ ɛɪ. 9. ɊȿɁɍɅɌȺɌɂ 91 Ɍɚɛɟɥɚ ɛɪ. 107. Ɋɟɡɭɥɬɚɬɢ ɢɫɩɢɬɢɜɚʃɚ ɞɢʁɚɝɧɨɫɬɢɱɤɨɝ ɩɨɬɟɧɰɢʁɚɥɚ ɭɪɢɧɚɪɧɟ ɤɨɧɰɟɧɬɪɚɰɢʁɟ KIM-1.0 ɢ KIM-1.0.ɤɨɪɢɝ ɡɚ ɤɚɪɰɢɧɨɦ ɫɜɟɬɥɢɯ ʄɟɥɢʁɚ ɛɭɛɪɟɝɚ ɉɚɪɚɦɟɬɚɪ AUC ROC*ɫɚ 95%CI LТkОlТСooН ratТo ɬɟɫɬ# KIM-1.0 83.92% (74.33%-93.51%) p = 2.192*10-7 KIM-1.0ɤɨɪɢɝ. 73.29% (60.52%-86.06%) p = 0.000876 *Area Under the Curve ROC (ɩɨ ɦɟɬɨɞɢ DeLong-a) #ɂɫɩɢɬɢɜɚʃɟ ɡɧɚɱɚʁɧɨɫɬɢ ɞɢʁɚɝɧɨɫɬɢɱɤɨɝ ɩɨɬɟɧɰɢʁɚɥɚ ɩɚɪɚɦɟɬɪɚ ɧɚ ɢɫɯɨɞ ɨɞ ɢɧɬɟɪɟɫɚ (ɩɪɢɫɭɫɬɜɨ ɤɚɪɰɢɧɨɦɚ ɫɜɟɬɥɢɯ ʄɟɥɢʁɚ ɛɭɛɪɟɝɚ) ɩɪɟɞɫɬɚɜʂɚ ɢɫɩɢɬɢɜɚʃɟ ɡɧɚɱɚʁɧɨɫɬɢ ɨɞɝɨɜɚɪɚʁɭʄɟ ɥɨɝɢɫɬɢɱɤɟ ɪɟɝɪɟɫɢʁɟ (Likelihood ratio ɬɟɫɬ). Ƚɪɚɮɢɤɨɧɛɪ. 9. ROC ɤɪɢɜɟ KIM1.0 ɢ KIM1.0.ɤɨɪɢɝ. ɡɚ ɩɪɢɫɭɫɬɜɨ ɤɚɪɰɢɧɨɦɚ ɫɜɟɬɥɢɯ ʄɟɥɢʁɚ ɛɭɛɪɟɝɚ Ʉɚɨ ɲɬɨ ɫɟ ɢɡ ɬɚɛɟɥɟ ɛɪ. 107. ɢ ɝɪɚɮɢɤɨɧɚ ɛɪ. 9. ɜɢɞɢ, ɩɚɪɚɦɟɬɪɢ KIM1.0 ɢ KIM1.0 ɤɨɪɢɝɨɜɚɧɨ, ɢɦɚʁɭ ɫɬɚɬɢɫɬɢɱɤɢ ɡɧɚɱɚʁɚɧ ɞɢʁɚɝɧɨɫɬɢɱɤɢ ɩɨɬɟɧɰɢʁɚɥ ɡɚ ɤɚɪɰɢɧɨɦ ɫɜɟɬɥɢɯ ʄɟɥɢʁɚ ɛɭɛɪɟɝɚ. Ɂɚ ɢɧɢɰɢʁɚɥɧɢɟ ɜɪɟɞɧɨɫɬɢ ɭɪɢɧɚɪɧɢɯ ɤɨɧɰɟɧɬɪɚɰɢʁɚ KIM-1 ɢ KIM-1 ɤɨɪɢɝɨɜɚɧɨ, ɢɫɩɢɬɢɜɚɧɟ ɫɭ ɞɢɫɤɪɢɦɢɧɚɰɢɨɧɟ ɜɪɟɞɧɨɫɬɢ ɡɚ ɩɪɢɫɭɫɬɜɨ ɤɚɪɰɢɧɨɦɚ ɫɜɟɬɥɢɯ ʄɟɥɢʁɚ ɛɭɛɪɟɝɚ. ɍ ɬɚɛɟɥɢ ɛɪ. 108. ɢ ɧɚ ɝɪɚɮɢɤɨɧɭ ɛɪ. 10., ɩɪɢɤɚɡɚɧɢ ɫɭ ɞɨɛɢʁɟɧɢ ɪɟɡɭɥɬɚɬɢ. 0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1 0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1 ROC KIM-1.0 ROC KIM-1.0 ко̛̬̐. 1-ɋɩɟɰɢɮɢɱɧɨɫɬ ɋɟ ɧɡɢ ɬɢ ɜɧ ɨɫɬ ɊȿɁɍɅɌȺɌɂ 92 Ɍɚɛɟɥɚ ɛɪ. 108. ɇɚʁɛɨʂɟ ɝɪɚɧɢɱɧɟ ɜɪɟɞɧɨɫɬɢ ɢɫɩɢɬɢɜɚɧɢɯ ɩɚɪɚɦɟɬɚɪɚ ɡɚ ɩɪɢɫɭɫɬɜɨ ɤɚɪɰɢɧɨɦɚ ɫɜɟɬɥɢɯ ʄɟɥɢʁɚ ɛɭɛɪɟɝɚ ɢ ɩɪɢɩɚɞɚʁɭʄɚ ɫɟɧɡɢɬɢɜɧɨɫɬ ɢ ɫɩɟɰɢɮɢɱɧɨɫɬ, ɫɚ ɨɞɝɨɜɚɪɚʁɭʄɢɦ 95%CI ɉɚɪɚɦɟɬɚɪ ɇɚʁɛɨʂɚ ɝɪɚɧɢɱɧɚ ɜɪɟɞɧɨɫɬ* ɋɟɧɡɢɬɢɜɧɨɫɬ (95%CI) (%) ɋɩɟɰɢɮɢɱɧɨɫɬ (95%CI) (%) KIM1.0 0.255 64.1 (48.72-79.49) 95.83 (87.5-100) KIM1.0.ɤɨɪɢɝ. 0.226 71.79 (56.41-87.18) 70.83 (50.0-87.5) *ȼɪɟɞɧɨɫɬ ɡɚ ɤɨʁɭ ʁɟ ɩɨɫɬɢɝɧɭɬɚ ɦɚɤɫɢɦɚɥɧɚ ɫɟɧɡɢɬɢɜɧɨɫɬ ɢ ɫɩɟɰɢɮɢɱɧɨɫɬ Ƚɪɚɮɢɤɨɧ ɛɪ.10. ɇɚʁɛɨʂɟ ɝɪɚɧɢɱɧɟ ɜɪɟɞɧɨɫɬɢ ɢɫɩɢɬɢɜɚɧɢɯ ɩɚɪɚɦɟɬɚɪɚ ɡɚ ɩɪɢɫɭɫɬɜɨ ɤɚɪɰɢɧɨɦɚ ɫɜɟɬɥɢɯ ʄɟɥɢʁɚ ɛɭɛɪɟɝɚ (ɥɟɜɨ: KIM-1.0; ɞɟɫɧɨ: KIM-1.0 ɤɨɪɢɝɨɜɚɧɨ) Ʉɚɨ ɲɬɨ ɫɟ ɢɡ ɬɚɛɟɥɟ ɛɪ. 108. ɢ ɝɪɚɮɢɤɨɧɚ ɛɪ. 10. ɜɢɞɢ, ɢɧɢɰɢʁɚɥɧɚ ɧɟɤɨɪɢɝɨɜɚɧɚ ɜɪɟɞɧɨɫɬ KIM-1 ɡɚ ɤɨʁɭ ʁɟ ɩɨɫɬɢɝɧɭɬɚ ɦɚɤɫɢɦɚɥɧɚ ɫɟɧɡɢɬɢɜɧɨɫɬ (64,1%) ɢ ɫɩɟɰɢɮɢɱɧɨɫɬ (95,83%) ɢɡɧɨɫɢ 0,255 ng/ml. ɂɧɢɰɢʁɚɥɧɚ ɤɨɪɢɝɨɜɚɧɚ ɜɪɟɞɧɨɫɬ KIM-1 ɡɚ ɤɨʁɭ ʁɟ ɩɨɫɬɢɝɧɭɬɚ ɦɚɤɫɢɦɚɥɧɚ ɫɟɧɡɢɬɢɜɧɨɫɬ (71,79%) ɢ ɫɩɟɰɢɮɢɱɧɨɫɬ (70,83%) ɢɡɧɨɫɢ 0,226 ng/mgUcr. 4.7.2. ɂɫɩɢɬɢɜɚʃɟ ɞɢʁɚɝɧɨɫɬɢɱɤɨɝ ɩɨɬɟɧɰɢʁɚɥɚ ɩɪɟɨɩɟɪɚɬɢɜɧɢɯ ɜɪɟɞɧɨɫɬɢ ɭɪɢɧɚɪɧɟ ɤɨɧɰɟɧɬɪɚɰɢʁɟ AQP-1 ɡɚ ɤɚɪɰɢɧɨɦ ɫɜɟɬɥɢɯ ʄɟɥɢʁɚ ɛɭɛɪɟɝɚ Ɉɞ ɢɧɬɟɪɟɫɚ ɡɚ ɨɜɨ ɢɫɬɪɚɠɢɜɚʃɟ ɛɢɥɨ ʁɟ ɢɫɩɢɬɢɜɚʃɟ ɞɢʁɚɝɧɨɫɬɢɱɤɨɝ ɩɨɬɟɧɰɢʁɚɥɚ ɢɧɢɰɢʁɚɥɧɢɯ ɜɪɟɞɧɨɫɬɢ ɭɪɢɧɚɪɧɟ ɤɨɧɰɟɧɬɪɚɰɢʁɟ AQP-1 ɡɚ ɤɚɪɰɢɧɨɦ ɫɜɟɬɥɢɯ ʄɟɥɢʁɚ ɛɭɛɪɟɝɚ. Ɋɟɡɭɥɬɚɬɢ ɫɬɚɬɢɫɬɢɱɤɟ ɚɧɚɥɢɡɟ ɫɭ ɩɪɢɤɚɡɚɧɢ ɭ ɬɚɛɟɥɢ ɛɪ. 109. ɢ ɧɚ ɝɪɚɮɢɤɨɧɭ ɛɪ. 11. Ɍɚɛɟɥɚ ɛɪ. 109. Ɋɟɡɭɥɬɚɬɢ ɢɫɩɢɬɢɜɚʃɚ ɞɢʁɚɝɧɨɫɬɢɱɤɨɝ ɩɨɬɟɧɰɢʁɚɥɚ ɭɪɢɧɚɪɧɟ ɤɨɧɰɟɧɬɪɚɰɢʁɟ AQP-1.0 ɢ AQP-1.0 ɤɨɪɢɝ. ɡɚ ɤɚɪɰɢɧɨɦ ɫɜɟɬɥɢɯ ʄɟɥɢʁɚ ɛɭɛɪɟɝɚ ɉɚɪɚɦɟɬɚɪ AUC ROC*ɫɚ 95%CI Likelihood ratio test# AQP-1.0 49.68% (33.82%-65.54%) p = 0.6797 AQP-1.0 ɤɨɪɢɝ. 66.35% (52.06%-80.64%) p = 0.02741 *Area Under the Curve ROC (ɩɨ ɦɟɬɨɞɢ DeLong-a) ɊȿɁɍɅɌȺɌɂ 93 Ƚɪɚɮɢɤɨɧ ɛɪ. 11. ROC ɤɪɢɜɟ AQP1.0 i AQP1.0.ɤɨɪɢɝ. ɡɚ ɩɪɢɫɭɫɬɜɨ ɤɚɪɰɢɧɨɦɚ ɫɜɟɬɥɢɯ ʄɟɥɢʁɚ ɛɭɛɪɟɝɚ Ʉɚɨ ɲɬɨ ɫɟ ɢɡ ɬɚɛɟɥɟ ɛɪ. 109. ɢ ɝɪɚɮɢɤɨɧɚ ɛɪ. 11 ɜɢɞɢ, ɩɚɪɚɦɟɬɚɪ AQP-1.0 ɤɨɪɢɝɨɜɚɧ ɢɦɚ ɫɬɚɬɢɫɬɢɱɤɢ ɡɧɚɱɚʁɚɧ ɞɢʁɚɝɧɨɫɬɢɱɤɢ ɩɨɬɟɧɰɢʁɚɥ ɡɚ ɤɚɪɰɢɧɨɦ ɫɜɟɬɥɢɯ ʄɟɥɢʁɚ ɛɭɛɪɟɝɚ. ɂɫɩɢɬɢɜɚʃɟɦ ɧɟɤɨɪɢɝɨɜɚɧɟ ɜɪɟɞɧɨɫɬɢ AQP-1.0 ɧɢʁɟ ɞɨɛɢʁɟɧ ɫɬɚɬɢɫɬɢɱɤɢ ɡɧɚɱɚʁɚɧ ɞɢʁɚɝɧɨɫɬɢɱɤɢ ɩɨɬɟɧɰɢʁɚɥ ɡɚ ɤɚɪɰɢɧɨɦ ɫɜɟɬɥɢɯ ʄɟɥɢʁɚ ɛɭɛɪɟɝɚ. Ɂɚ ɢɧɢɰɢʁɚɥɧɟ ɜɪɟɞɧɨɫɬɢ ɭɪɢɧɚɪɧɢɯ ɤɨɧɰɟɧɬɪɚɰɢʁɚ AQP-1.0 ɢ AQP-1.0 ɤɨɪɢɝɨɜɚɧɨ, ɢɫɩɢɬɢɜɚɧɟ ɫɭ ɞɢɫɤɪɢɦɢɧɚɰɢɨɧɟ ɜɪɟɞɧɨɫɬɢ ɡɚ ɩɪɢɫɭɫɬɜɨ ɤɚɪɰɢɧɨɦɚ ɫɜɟɬɥɢɯ ʄɟɥɢʁɚ ɛɭɛɪɟɝɚ. ɍ ɬɚɛɟɥɢ ɛɪ. 110. ɢ ɧɚ ɝɪɚɮɢɤɨɧɢɦɚ ɛɪ. 12. ɢ 13., ɩɪɢɤɚɡɚɧɢ ɫɭ ɞɨɛɢʁɟɧɢ ɪɟɡɭɥɬɚɬɢ. Ɍɚɛɟɥɚ ɛɪ. 110. ɇɚʁɛɨʂɟ ɝɪɚɧɢɱɧɟ ɜɪɟɞɧɨɫɬɢ ɢɫɩɢɬɢɜɚɧɢɯ ɩɚɪɚɦɟɬɚɪɚ ɡɚ ɩɪɢɫɭɫɬɜɨ ɤɚɪɰɢɧɨɦɚ ɫɜɟɬɥɢɯ ʄɟɥɢʁɚ ɛɭɛɪɟɝɚ ɢ ɩɪɢɩɚɞɚʁɭʄɚ ɫɟɧɡɢɬɢɜɧɨɫɬ ɢ ɫɩɟɰɢɮɢɱɧɨɫɬ,ɫɚ ɨɞɝɨɜɚɪɚʁɭʄɢɦ 95%CI ɉɚɪɚɦɟɬɚɪ ɇɚʁɛɨʂɚ ɝɪɚɧɢɱɧɚ ɜɪɟɞɧɨɫɬ* ɋɟɧɡɢɬɢɜɧɨɫɬ (95%CI) (%) ɋɩɟɰɢɮɢɱɧɨɫɬ (95%CI) (%) AQP1.0 0.094 79.49 (66.67-92.31) 31.75 (20.83-58.33) AQP1.0.ɤɨɪɢɝ. 0.081 56.41 (41.03-71.79) 75 (58.33-91.67) *ȼɪɟɞɧɨɫɬ ɡɚ ɤɨʁɭ ʁɟ ɩɨɫɬɢɝɧɭɬɚ ɦɚɤɫɢɦɚɥɧɚ ɫɟɧɡɢɬɢɜɧɨɫɬ ɢ ɫɩɟɰɢɮɢɱɧɨɫɬ 0.0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1.0 0.0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1.0 ROC aqp1.0 ROC aqp1.0.ко̛̬̐. 1-Спец̛ф̛чно̭т Се н̚ ̛т̛ ̏н о̭т ɊȿɁɍɅɌȺɌɂ 94 Ƚɪɚɮɢɤɨɧ ɛɪ. 12. ɇɚʁɛɨʂa ɝɪɚɧɢɱɧɚ ɜɪɟɞɧɨɫɬ ɚɩɫɨɥɭɬɧɟ ɤɨɧɰɟɧɬɪɚɰɢʁɟ AQP-1.0 ɡɚ ɩɪɢɫɭɫɬɜɨ ɤɚɪɰɢɧɨɦɚ ɫɜɟɬɥɢɯ ʄɟɥɢʁɚ ɛɭɛɪɟɝɚ Ƚɪɚɮɢɤɨɧ ɛɪ.13. ɇɚʁɛɨʂa ɝɪɚɧɢɱɧɚ ɜɪɟɞɧɨɫɬ ɤɨɪɢɝɨɜɚɧɟ ɤɨɧɰɟɧɬɪɚɰɢʁɟ AQP-1.0 ɡɚ ɩɪɢɫɭɫɬɜɨ ɤɚɪɰɢɧɨɦɚ ɫɜɟɬɥɢɯ ʄɟɥɢʁɚ ɛɭɛɪɟɝɚ Ʉɚɨ ɲɬɨ ɫɟ ɢɡ ɬɚɛɟɥɟ ɛɪ. 110. ɢ ɝɪɚɮɢɤɨɧɚ ɛɪ. 12. ɢ 13. ɜɢɞɢ, ɢɧɢɰɢʁɚɥɧɚ ɧɟɤɨɪɢɝɨɜɚɧɚ ɜɪɟɞɧɨɫɬ AQP-1 ɡɚ ɤɨʁɭ ʁɟ ɩɨɫɬɢɝɧɭɬɚ ɦɚɤɫɢɦɚɥɧɚ ɫɟɧɡɢɬɢɜɧɨɫɬ (79,49%) ɢ ɫɩɟɰɢɮɢɱɧɨɫɬ (31,75%) ɢɡɧɨɫɢ 0,094 ng/ml. ɂɧɢɰɢʁɚɥɧɚ ɤɨɪɢɝɨɜɚɧɚ ɜɪɟɞɧɨɫɬ AQP-1 ɡɚ ɤɨʁɭ ʁɟ ɩɨɫɬɢɝɧɭɬɚ ɦɚɤɫɢɦɚɥɧɚ ɫɟɧɡɢɬɢɜɧɨɫɬ (56,41%) ɢ ɫɩɟɰɢɮɢɱɧɨɫɬ (75%) ɢɡɧɨɫɢ 0,081 ng/mgUcr. 0.0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1.0 0.0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1.0 ROC aqp1.0 1-Спец̛ф̛чно̭т Се н̚ ̛т̛ ̏н о̭т 0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1 0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1 ROC aqp1.0.korig 1-Спец̛ф̛чно̭т Се н̚ ̛т̛ ̏н о̭т ɊȿɁɍɅɌȺɌɂ 95 4.7.3. Ʉɨɦɩɚɪɚɰɢʁɚ ɞɢʁɚɝɧɨɫɬɢɱɤɢɯ ɩɨɬɟɧɰɢʁɚɥɚ ɢɧɢɰɢʁɚɥɧɢɯ ɜɪɟɞɧɨɫɬɢ uKIM-1 ɢ uAQP-1 ɡɚ ɤɚɪɰɢɧɨɦ ɫɜɟɬɥɢɯ ʄɟɥɢʁɚ ɛɭɛɪɟɝɚ Ɉɞ ɢɧɬɟɪɟɫɚ ɡɚ ɨɜɨ ɢɫɬɪɚɠɢɜɚʃɟ ʁɟ ɛɢɥɨ ɩɨɪɟђɟʃɟ ɞɢʁɚɝɧɨɫɬɢɱɤɢɯ ɩɨɬɟɧɰɢʁɚɥɚ ɜɪɟɞɧɨɫɬɢ ɭɪɢɧɚɪɧɢɯ ɤɨɧɰɟɧɬɪɚɰɢʁɚ KIM-1 ɢ AQP-1 ɡɚ ɩɪɢɫɭɫɬɜɨ ɤɚɪɰɢɧɨɦɚ ɫɜɟɬɥɢɯ ʄɟɥɢʁɚ ɛɭɛɪɟɝɚ. Ɋɟɡɭɥɬɚɬɢ ɫɬɚɬɢɫɬɢɱɤɟ ɚɧɚɥɢɡɟ ɫɭ ɩɪɢɤɚɡɚɧɢ ɭ ɬɚɛɟɥɢ ɛɪ. 111. ɢ ɧɚ ɝɪɚɮɢɤɨɧɭ ɛɪ. 14. Ɍɚɛɟɥɚ ɛɪ. 111. Ɋɟɡɭɥɬɚɬɢ ɩɨɪɟђɟʃɚ ɞɢʁɚɝɧɨɫɬɢɱɤɨɝ ɩɨɬɟɧɰɢʁɚɥɚ ɭɪɢɧɚɪɧɟ ɤɨɧɰɟɧɬɪɚɰɢʁɟ KIM-1.0, KIM-1.0.ɤɨɪɢɝ., AQP-1.0 ɢ AQP-1.0.ɤɨɪɢɝ.ɡɚ ɤɚɪɰɢɧɨɦ ɫɜɟɬɥɢɯ ʄɟɥɢʁɚ ɛɭɛɪɟɝɚ ɉɚɪɨɜɢ ɩɚɪɚɦɟɬɚɪɚ ɢɫɬɨɝ ɬɢɩɚ DeLong ɬɟɫɬ* KIM-1.0 vs KIM-1.0.ɤɨɪɢɝ. z =1.613152; p = 0.1067 AQP-1.0 vs AQP-1.0.ɤɨɪɢɝ. z = 1.991674; p = 0.0464 ɉɚɪɨɜɢ ɩɚɪɚɦɟɬɚɪɚ ɪɚɡɥɢɱɢɬɨɝ ɬɢɩɚ Bootstrap ɬɟɫɬ* KIM-1.0 vs AQP-1.0 D = 3.830071; p = 0.0001 KIM-1.0 vs AQP-1.0.ɤɨɪɢɝ. D = 2.56633; p = 0.0103 KIM-1.0.ɤɨɪɢɝ. vs AQP-1.0 D = 2.410762; p = 0.0160 KIM-1.0.ɤɨɪɢɝ. vs AQP-1.0.ɤɨɪɢɝ. D = 0.6105273; p = 0.5415 *Ɂɚ ɡɚɜɢɫɧɟ ɭɡɨɪɤɟ (ɬј. ROC ɤɪɢɜɟ ɡɚ ɡɚɜɢɫɧɟ ɭɡɨɪɤɟ) Ƚɪɚɮɢɤɨɧɛɪ. 14. ROC ɤɪɢɜɟ KIM-1.0, KIM-1.0.ɤɨɪɢɝ., AQP-1.0 i AQP-1.0.ɤɨɪɢɝ. ɡɚ ɤɚɪɰɢɧɨɦ ɫɜɟɬɥɢɯ ʄɟɥɢʁɚ ɛɭɛɪɟɝɚ Ʉɚɨ ɲɬɨ ɫɟ ɢɡ ɬɚɛɟɥɟ ɛɪ. 111. ɢ ɝɪɚɮɢɤɨɧɚ ɛɪ. 14.ɜɢɞɢ, ɩɨɪɟђɟʃɟɦ ɩɚɪɨɜɚ ɩɚɪɚɦɟɬɚɪɚ ɢɫɬɨɝ ɬɢɩɚ ɧɢʁɟ ɞɨɛɢʁɟɧɚ ɫɬɚɬɢɫɬɢɱɤɢ ɡɧɚɱɚʁɧɚ ɪɚɡɥɢɤɚ ɭ ɞɢʁɚɝɧɨɫɬɢɱɤɨɦ ɩɨɬɟɧɰɢʁɚɥɭ ɢɡɦɟђɭ ɜɪɟɞɧɨɫɬɢ ɧɟɤɨɪɢɝɨɜɚɧɟ ɢ ɤɨɪɢɝɨɜɚɧɟ ɤɨɧɰɟɧɬɪɚɰɢʁɟ KIM-1.0. ɉɨɪɟђɟʃɟɦ 0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1 0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1 ROC KIM1.0 ROC KIM1.0.ко̛̬̐. ROC AQP1.0 ROC AQP1.0.ко̛̬̐. 1-Спец̛ф̛чно̭т Се н̚ ̛т̛ ̏н о̭т ɊȿɁɍɅɌȺɌɂ 96 ɧɟɤɨɪɢɝɨɜɚɧɟ ɢ ɤɨɪɢɝɨɜɚɧɟ ɤɨɧɰɟɧɬɪɚɰɢʁɟ AQP-1.0 ɞɨɛɢʁɟɧɚ ʁɟ ɫɬɚɬɢɫɬɢɱɤɢ ɡɧɚɱɚʁɧɚ ɪɚɡɥɢɤɚ ɭ ɞɢʁɚɝɧɨɫɬɢɱɤɨɦ ɩɨɬɟɧɰɢʁɚɥɭ. ɉɨɪɟђɟʃɟɦ ɩɚɪɨɜɚ ɩɚɪɚɦɟɬɚɪɚ ɪɚɡɥɢɱɢɬɨɝ ɬɢɩɚ ɧɢʁɟ ɞɨɛɢʁɟɧɚ ɫɬɚɬɢɫɬɢɱɤɢ ɡɧɚɱɚʁɧɚ ɪɚɡɥɢɤɚ ɭ ɞɢʁɚɝɧɨɫɬɢɱɤɨɦ ɩɨɬɟɧɰɢʁɚɥɭ ɢɡɦɟђɭ ɤɨɪɢɝɨɜɚɧɢɯ ɜɪɟɞɧɨɫɬɢ KIM-1.0 ɢ AQP-1.0. ɉɨɪɟђɟʃɟɦ ɨɫɬɚɥɢɯ ɩɚɪɨɜɚ ɩɚɪɚɦɟɬɚɪɚ ɪɚɡɥɢɱɢɬɨɝ ɬɢɩɚ (KIM-1.0ɭ ɩɨɪɟђɟʃɭ ɫɚAQP-1.0, KIM-1.0 ɭ ɩɨɪɟђɟʃɭ ɫɚ AQP-1.0 ɤɨɪɢɝɨɜɚɧɨ, KIM-1.0 ɤɨɪɢɝɨɜɚɧɨɭ ɩɨɪɟђɟʃɭ ɫɚ AQP-1.0) ɞɨɛɢʁɟɧɚ ʁɟ ɫɬɚɬɢɫɬɢɱɤɢ ɡɧɚɱɚʁɧɚ ɪɚɡɥɢɤɚ ɭ ɞɢʁɚɝɧɨɫɬɢɱɤɨɦ ɩɨɬɟɧɰɢʁɚɥɭ. ȾɂɋɄɍɋɂȳȺ 97 5. ȾɂɋɄɍɋɂȳȺ ɂɧɰɢɞɟɧɰɚ ɄȻ ɩɨɤɚɡɭʁɟ ɤɨɧɫɬɚɧɬɚɧ ɩɨɪɚɫɬ ɩɨɫɥɟɞʃɢɯ ɞɟɰɟɧɢʁɚ, ɲɬɨ ʁɟ ɞɟɥɨɦ ɭɫɥɨɜʂɟɧɨ ɩɨɜɟʄɚɧɨɦ ɩɪɢɦɟɧɨɦ ɪɚɞɢɨɥɨɲɤɢɯ ɞɢʁɚɝɧɨɫɬɢɱɤɢɯ ɩɪɨɰɟɞɭɪɚ ɢ ɫɥɭɱɚʁɧɢɦ ɨɬɤɪɢʄɟɦ ɫɨɥɢɞɧɢɯ ɬɭɦɨɪɫɤɢɯ ɩɪɨɦɟɧɚ ɧɚ ɛɭɛɪɟɝɭ189. ɍɩɪɤɨɫ ɩɪɢɦɟɧɢ ɫɚɜɪɟɦɟɧɢɯ ɞɢʁɚɝɧɨɫɬɢɱɤɢɯ ɩɪɨɰɟɞɭɪɚ ɢ ɭɬɜɪђɢɜɚʃɚ ɩɪɨɝɧɨɫɬɢɱɤɢɯ ɮɚɤɬɨɪɚ, 10% ɞɨ 30% ɥɨɤɚɥɢɡɨɜɚɧɢɯ ɬɭɦɨɪɚ ʄɟ ɦɟɬɚɫɬɚɡɢɪɚɬɢ ɭɧɭɬɚɪ ɩɪɜɟ 3 ɝɨɞɢɧɟ, ɫɦɚʃɭʁɭʄɢ 5-ɝɨɞɢɲʃɟ ɩɪɟɠɢɜʂɚɜɚʃɟ ɫɚ 60% ɧɚ ɦɚʃɟ ɨɞ 10%11. Ɋɚɧɚ ɞɢʁɚɝɧɨɡɚ ɭ ɮɚɡɢ ɨɪɝɚɧ-ɨɝɪɚɧɢɱɟɧɟ ɛɨɥɟɫɬɢ ɭɞɪɭɠɟɧɚ ʁɟ ɫɚ ɞɨɛɪɨɦ ɩɪɨɝɧɨɡɨɦ, ɚɥɢ ɫɟ ɨɜɚʁ ɬɢɩ ɤɚɪɰɢɧɨɦɚ ɤɚɪɚɤɬɟɪɢɲɟ ɨɞɫɭɫɬɜɨɦ ɪɚɧɢɯ ɫɢɦɩɬɨɦɚ ɢ ɡɧɚɤɨɜɚ ɛɨɥɟɫɬɢ, ɤɚɨ ɢ ɥɚɛɨɪɚɬɨɪɢʁɫɤɢɯ ɚɛɧɨɪɦɚɥɧɨɫɬɢ77.Ɉɝɪɚɧɢɱɟɧɟ ɦɨɝɭʄɧɨɫɬɢ ɡɚ ɞɢʁɚɝɧɨɡɭ ɬɭɦɨɪɚ ɛɭɛɪɟɝɚ ɭɤɚɡɭʁɭ ɧɚ ɧɟɨɩɯɨɞɧɨɫɬ ɪɚɡɜɨʁɚ ɫɟɧɡɢɬɢɜɧɢɯ ɛɢɨɦɚɪɤɟɪɚ ɡɚ ɫɤɪɢɧɢɧɝ ɢ ɩɪɚʄɟʃɟ ɬɭɦɨɪɫɤɢɯ ɩɪɨɦɟɧɚ ɭ ɛɭɛɪɟɝɭ, ɚ ɤɨʁɢ ɛɢ ɦɨɝɥɢ ɞɚ ɭɤɚɠɭ ɧɚ ɩɪɢɪɨɞɭ ɩɪɨɦɟɧɟ ɢ ɧɚɱɢɧ ʃɟɧɨɝ ɥɟɱɟʃɚ. ȳɨɲ ɭɜɟɤ ɧɟ ɩɨɫɬɨʁɢ ɢɞɟɚɥɚɧ ɛɢɨɦɚɪɤɟɪ ɡɚ ɞɢʁɚɝɧɨɡɭ ɤɚɪɰɢɧɨɦɚ ɛɭɛɪɟɝɚ, ɧɢɬɢ ɧɚɱɢɧ ɡɚ ɩɨɩɭɥɚɰɢɨɧɢ ɫɤɪɢɧɢɧɝ ɨɜɟ ɛɨɥɟɫɬɢ. ɋ ɨɛɡɢɪɨɦ ɞɚ ɫɄȻ ɩɪɟɞɫɬɚɜʂɚ ɧɚʁɱɟɲʄɭ ɦɟɬɚɫɬɚɬɫɤɭ ɢ ɚɝɪɟɫɢɜɧɭ ɮɨɪɦɭ ɄȻ, ɧɟɨɩɯɨɞɧɢ ɫɭ ɧɨɜɢ ɢ ɩɨɭɡɞɚɧɢ ɞɢʁɚɝɧɨɫɬɢɱɤɢ ɬɟɫɬɨɜɢ ɡɚ ɨɬɤɪɢɜɚʃɟ ɛɨɥɟɫɬɢ ɭ ɩɪɟɦɟɬɚɫɬɚɬɫɤɨɦ ɩɟɪɢɨɞɭ96. ɉɨɭɡɞɚɧ ɭɪɢɧɚɪɧɢ ɬɟɫɬ ɡɚ ɫɄȻ ɦɨɝɚɨ ɛɢ ɞɚ ɢɦɚ ɡɧɚɱɚʁ ɭ ɫɤɪɢɧɢɧɝɭ ɩɚɰɢʁɟɧɚɬɚ ɫɚ ɜɢɫɨɤɢɦ ɪɢɡɢɤɨɦ ɡɚ ɨɛɨʂɟɜɚʃɟ ɨɞ ɨɜɟ ɜɪɫɬɟ ɬɭɦɨɪɚ ɢ ɤɚɨ ɞɨɞɚɬɧɢ ɦɚɪɤɟɪ ɡɚ ɨɞɝɨɜɨɪ ɧɚ ɬɟɪɚɩɢʁɭ ɢ ɩɨɫɬ- ɬɟɪɚɩɢʁɫɤɨ ɩɪɚʄɟʃɟ119. Ⱦɨ ɫɚɞɚ ɫɩɪɨɜɟɞɟɧɚ ɢɫɩɢɬɢɜɚʃɚ ɩɨɤɚɡɚɥɚ ɫɭ ɩɨɜɟʄɚɧɭ ɟɤɫɩɪɟɫɢʁɭ ɨɞɪɟђɟɧɢɯ ɩɪɨɬɟɢɧɚ ɭ ɬɭɦɨɪɫɤɨɦ ɬɤɢɜɭ ɯɢɪɭɪɲɤɢ ɨɞɫɬɪɚʃɟɧɢɯɫɄȻ. ɇɚ ɛɚɡɢ ɩɨɬɟɧɰɢʁɚɥɚ ɡɚ ɭɪɢɧɚɪɧɭ ɟɤɫɤɪɟɰɢʁɭ ɨɜɢɯ ɭɫɯɨɞɧɨ ɪɟɝɭɥɢɫɚɧɢɯ ɩɪɨɬɟɢɧɚ, ɢɫɩɢɬɢɜɚɧɨ ʁɟ ɧɟɤɨɥɢɤɨ ɩɨɬɟɧɰɢʁɚɥɧɢɯ ɛɢɨɦɚɪɤɟɪɚ ɨɞ ɡɧɚɱɚʁɚ ɡɚ ɞɢʁɚɝɧɨɡɭ, ɚ ɩɨ ɫɜɨʁɨʁ ɫɟɧɡɢɬɢɜɧɨɫɬɢ ɢ ɫɩɟɰɢɮɢɱɧɨɫɬɢ ɢɡɞɜɨʁɢɥɢ ɫɭ ɫɟ ɩɪɨɬɟɢɧ 1 ɨɲɬɟʄɟʃɚ ɛɭɛɪɟɝɚ (KIM-1) ɢ ɚɤɜɚɩɨɪɢɧ 1 (AQP- 1). 5.1. Ʉɥɢɧɢɱɤɟ ɤɚɪɚɤɬɟɪɢɫɬɢɤɟ, ɮɚɤɬɨɪɢ ɪɢɡɢɤɚ ɢ ɫɢɦɩɬɨɦɢ ɩɚɪɚɧɟɨɩɥɚɫɬɢɱɧɨɝ ɫɢɧɞɪɨɦɚ ɢɫɩɢɬɢɜɚɧɟ ɝɪɭɩɟ ɨɛɨɥɟɥɢɯ ɨɞ ɤɚɪɰɢɧɨɦɚ ɫɜɟɬɥɢɯ ʄɟɥɢʁɚ ɛɭɛɪɟɝɚ Ʉɚɪɰɢɧɨɦ ɫɜɟɬɥɢɯ ʄɟɥɢʁɚ ɛɭɛɪɟɝɚ ɢɥɢ ɫɜɟɬɥɨʄɟɥɢʁɫɤɢ ɤɚɪɰɢɧɨɦ ɛɭɛɪɟɝɚ (ɫɄȻ) ɫɟ ɧɚʁɱɟɲʄɟ ʁɚɜʂɚ ɤɨɞ ɨɫɨɛɚ ɭ ɩɟɪɢɨɞɭ ɢɡɦɟђɭ ɩɟɬɟ ɢ ɫɟɞɦɟ ɞɟɰɟɧɢʁɟ ɠɢɜɨɬɚ, ɫɚ ɩɪɨɫɟɱɧɨɦ ɠɢɜɨɬɧɨɦ ɞɨɛɢ ɨɞ 66 ɝɨɞɢɧɚ ɭ ɜɪɟɦɟ ɞɢʁɚɝɧɨɡɟ190. ɉɪɨɫɟɱɧɚ ɠɢɜɨɬɧɚ ɞɨɛ ɨɛɨɥɟɥɢɯ ɭ ɧɚɲɨʁ ɝɪɭɩɢ ɢɫɩɢɬɚɧɢɤɚ ɛɢɥɚ ʁɟ ɦɚʃɚ ɢ ɢɡɧɨɫɢɥɚ ʁɟ ɭ ɜɪɟɦɟ ɞɢʁɚɝɧɨɡɟ 54,24 ɝɨɞɢɧɟ, ɩɪɢ ɱɟɦɭ ʁɟ ɧɚʁɦɥɚђɢ ɩɚɰɢʁɟɧɬ ɢɦɚɨ 35 ɝɨɞɢɧɚ, ɚ ɧɚʁɫɬɚɪɢʁɢ 77 ɝɨɞɢɧɚ. ȼɟʄɢɧɭ ɩɚɰɢʁɟɧɚɬɚ, 29(70,73%) ɱɢɧɢɥɟ ɫɭ ɨɫɨɛɟ ɫɬɚɪɢʁɟ ɨɞ 50 ɝɨɞɢɧɚ, ɚ 12 (29,27%) ɨɛɨɥɟɥɢɯ ɫɭ ɛɢɥɢ ɦɥɚђɢ ɨɞ 50 ɝɨɞɢɧɚ. ɂɧɰɢɞɟɧɰɚ ɨɛɨʂɟɜɚʃɚ ɨɞɫɄȻ ʁɟ ɞɜɚ ɞɨ ɬɪɢ ɩɭɬɚ ɜɢɲɚ ɤɨɞ ɨɫɨɛɚ ɦɭɲɤɨɝ ɩɨɥɚ ɢ ɧɟɲɬɨ ɜɢɲɚ ɤɨɞ ɨɫɨɛɚ ɰɪɧɟ ɪɚɫɟ11.Ⱦɨ ɫɚɞɚ ɫɩɪɨɜɟɞɟɧɟ ɫɬɭɞɢʁɟ ɩɨɤɚɡɚɥɟ ɫɭ ɫɥɢɱɧɭ ɞɢɫɬɪɢɛɭɰɢʁɭ ɩɨɞɬɢɩɨɜɚɄȻ ɩɪɟɦɚ ɩɨɥɭ, ɫɚ ɨɛʁɚɜʂɟɧɢɦ ɨɞɧɨɫɨɦ ɨɛɨʂɟɜɚʃɚ ɢɡɦɟђɭ ɦɭɲɤɨɝ ɢ ɠɟɧɫɤɨɝ ɩɨɥɚ 1,5:1 ɤɨɞɨɛɨɥɟɥɢɯ ɨɞ ɫɄȻ191. ɂ ɭ ɧɚɲɨʁ ɝɪɭɩɢ ɨɛɨɥɟɥɢɯ ɞɨɛɢʁɟɧɚ ʁɟ ɫɥɢɱɚɧ ɨɞɧɨɫ ɢɡɦɟђɭ ɩɨɥɨɜɚ. ȼɟʄɢɧɭ ɨɛɨɥɟɥɢɯ ɱɢɧɢɥɟ ɫɭ ɨɫɨɛɟ ɦɭɲɤɨɝ ɩɨɥɚ, ʃɢɯ 26 (63,41%), ɞɨɤ ʁɟ ȾɂɋɄɍɋɂȳȺ 98 ɨɫɨɛɚ ɠɟɧɫɤɨɝ ɩɨɥɚ ɛɢɥɨ 15 (36,59%), ɫɚ ɨɞɧɨɫɨɦ 1,74:1 ɭ ɤɨɪɢɫɬ ɦɭɲɤɨɝ ɩɨɥɚ. ɂɧɰɢɞɟɧɰɚ ɄȻ, ɤɨɝɚ ɭ 80% ɞɨ 90% ɫɥɭɱɚʁɟɜɚ ɱɢɧɢ ɫɄȻ, ʁɟ ɭ ɩɨɪɚɫɬɭ ɲɢɪɨɦ ɫɜɟɬɚ, ɫɚ ɡɚɛɟɥɟɠɟɧɨɦ ɧɚʁɜɢɲɨɦ ɫɬɨɩɨɦ ɨɛɨʂɟɜɚʃɚ ɭ ɋɟɜɟɪɧɨʁ Ⱥɦɟɪɢɰɢ ɢ ȿɜɪɨɩɢ192. Ɉɜɨ ɩɨɜɟʄɚʃɟ ɫɟ ɞɟɥɨɦ ɦɨɠɟ ɨɛʁɚɫɧɢɬɢ ɩɨɜɟʄɚɧɨɦ ɢɧɰɢɞɟɧɰɨɦ ɨɬɤɪɢɜɚʃɚ ɬɭɦɨɪɚ ɩɪɢɦɟɧɨɦ ɪɚɞɢɨɥɨɲɤɢɯ ɞɢʁɚɝɧɨɫɬɢɱɤɢɯ ɩɪɨɰɟɞɭɪɚ (ɭɥɬɪɚɡɜɭɤ, ɫɤɟɧɟɪ, ɦɚɝɧɟɬɧɚ ɪɟɡɨɧɚɧɰɚ), ɚ ɞɟɥɨɦ ɩɨɜɟʄɚɧɨɦ ɩɪɟɜɚɥɟɧɰɨɦ ɮɚɤɬɨɪɚ ɪɢɡɢɤɚ193. ɍɫɬɚɧɨɜʂɟɧɢ ɮɚɤɬɨɪɢ ɪɢɡɢɤɚ ɡɚ ɪɚɡɜɨʁ ɫɄȻ ɫɭ: ɝɨʁɚɡɧɨɫɬ, ɚɪɬɟɪɢʁɫɤɚ ɯɢɩɟɪɬɟɧɡɢʁɚ ɢ ɩɭɲɟʃɟ, ɩɪɢ ɱɟɦɭ ɨɤɨ 50% ɨɛɨɥɟɥɢɯ ɢɦɚ ɧɚʁɦɚʃɟ ʁɟɞɚɧ ɮɚɤɬɨɪ ɪɢɡɢɤɚ194,195. ɍ ɫɬɭɞɢʁɢ Benichou ɢ ɫɚɪ., ɚɪɬɟɪɢʁɫɤɚ ɯɢɩɟɪɬɟɧɡɢʁɚ ɤɚɨ ɮɚɤɬɨɪ ɪɢɡɢɤɚ ɛɢɥɚ ʁɟ ɩɪɢɫɭɬɧɚ ɤɨɞ 21% ɨɛɨɥɟɥɢɯ, ɢɫɬɢ ɩɪɨɰɟɧɚɬ ɦɨɝɚɨ ɫɟ ɩɪɢɩɢɫɚɬɢ ɩɪɟɤɨɦɟɪɧɨʁ ɬɟɥɟɫɧɨʁ ɬɟɠɢɧɢ ɤɚɨ ɮɚɤɬɨɪɭ ɪɢɡɢɤɚ, ɞɨɤ ʁɟ ɤɨɞ 18% ɨɛɨɥɟɥɢɯ ɮɚɤɬɨɪ ɪɢɡɢɤɚ ɛɢɥɨ ɩɭɲɟʃɟ196.Ɋɟɡɭɥɬɚɬɢ ɞɨɫɚɞɚɲʃɢɯ ɢɫɩɢɬɢɜɚʃɚ ɫɭ ɩɨɤɚɡɚɥɢ ɞɚ ɝɨʁɚɡɧɨɫɬ ɩɪɟɞɫɬɚɜʂɚ ɡɧɚɱɚʁɚɧ ɧɟɡɚɜɢɫɧɢ ɮɚɤɬɨɪ ɪɢɡɢɤɚ ɡɚ ɪɚɡɜɨʁ ɫɄȻ.ɋɬɭɞɢʁɚ ɤɨʁɚ ʁɟ ɚɧɚɥɢɡɢɪɚɥɚ ɪɟɡɭɥɬɚɬɟ 22 ɧɟɡɚɜɢɫɧɟ ɤɥɢɧɢɱɤɟ ɫɬɭɞɢʁɟ ɫɩɪɨɜɟɞɟɧɟ ɭ ɩɟɪɢɨɞɭ ɨɞ 1966. ɞɨ 1998. ɩɨɤɚɡɚɥɚ ʁɟ ɞɚ ɩɨɫɬɨʁɢ ʁɚɱɚ ɩɨɜɟɡɚɧɨɫɬ ɢɡɦɟђɭ ɩɨɜɟʄɚʃɚ BMI ɢ ɪɚɡɜɨʁɚ ɫɄȻ ɤɨɞ ɦɭɲɤɨɝ ɩɨɥɚ ɭ ɨɞɧɨɫɭ ɧɚ ɠɟɧɫɤɢ, ɤɚɨ ɢ ɞɚ ɪɟɥɚɬɢɜɧɢ ɪɢɡɢɤ ɡɚ ɨɛɚ ɩɨɥɚ ɢɡɧɨɫɢ 1,07 ɡɚ ɫɜɚɤɭ ʁɟɞɢɧɢɰɭ ɩɨɜɟʄɚʃɚ BMI197. Leiba ɢ ɫɚɪ. ɫɭ ɭ ɫɜɨʁɨʁ ɫɬɭɞɢʁɢ ɩɪɚʄɟʃɚ ɩɨɤɚɡɚɥɢ ɞɚ ʁɟ ɩɪɟɤɨɦɟɪɧɚ ɬɟɥɟɫɧɚ ɬɟɠɢɧɚ ɭ ɤɚɫɧɨʁ ɚɞɨɥɟɫɰɟɧɰɢʁɢ ɛɢɥɚ ɡɧɚɱɚʁɚɧ ɮɚɤɬɨɪ ɪɢɡɢɤɚ ɡɚ ɪɚɡɜɨʁ ɄȻ198. ȳɟɞɧɚ ɨɞ ɧɚʁɜɟʄɢɯ ɟɩɢɞɟɦɢɨɥɨɲɤɢɯ ɫɬɭɞɢʁɚ ɫɩɪɨɜɟɞɟɧɚ ɧɚ 900.000 ɨɞɪɚɫɥɢɯ ɢɫɩɢɬɚɧɢɤɚ ɭ ɋȺȾ ɭ ɩɟɪɢɨɞɭ ɩɪɚʄɟʃɚ ɨɞ 16 ɝɨɞɢɧɚ, ɩɨɤɚɡɚɥɚ ʁɟ ɩɨɜɟʄɚɧ ɪɢɡɢɤ ɡɚ ɪɚɡɜɨʁ ɄȻ ɢ ɤɨɞ ɦɭɲɚɤɚɪɚɰɚ (ɞɨ 1,7 ɩɭɬɚ) ɢ ɤɨɞ ɠɟɧɚ (ɞɨ 4,75 ɩɭɬɚ) ɫɚ ɩɪɟɤɨɦɟɪɧɨɦ ɬɟɥɟɫɧɨɦ ɬɟɠɢɧɨɦ199. ȼɟɥɢɤɚ ɩɪɨɫɩɟɤɬɢɜɧɚ ɲɜɟɞɫɤɚ ɫɬɭɞɢʁɚ ɭ ɬɪɚʁɚʃɭ ɨɞ 19 ɝɨɞɢɧɚ ɫɩɪɨɜɟɞɟɧɚ ʁɟ ɧɚ 365.552 ɨɫɨɛɟ ɦɭɲɤɨɝ ɩɨɥɚ, ɩɨɤɚɡɚɥɚ ʁɟ ɞɚ ɫɭ ɩɪɟɤɨɦɟɪɧɚ ɬɟɥɟɫɧɚ ɬɟɠɢɧɚ ɢɥɢ ɝɨʁɚɡɧɨɫɬ ɛɢɥɢ ɭɞɪɭɠɟɧɢ ɫɚ ɫɬɚɬɢɫɬɢɱɤɢ ɡɧɚɱɚʁɧɨ ɜɟʄɢɦ ɨɛɨʂɟɜɚʃɟɦ ɨɞ ɄȻ. Ɋɟɥɚɬɢɜɧɢ ɪɢɡɢɤ ɨɛɨʂɟɜɚʃɚ ɢɡɧɨɫɢɨ ʁɟ 1,28 ɡɚ ɨɫɨɛɟ ɫɚ ɩɪɟɤɨɦɟɪɧɨɦ ɬɟɥɟɫɧɨɦ ɬɟɠɢɧɨɦ ɢ 1,82 ɡɚ ɝɨʁɚɡɧɟ200. ɋɦɚɬɪɚ ɫɟ ɞɚ ɧɟɤɨɥɢɤɨ ɦɟɯɚɧɢɡɚɦɚ ɩɨɬɟɧɰɢʁɚɥɧɨ ɦɨɠɟ ɭɬɢɰɚɬɢ ɧɚ ɪɚɡɜɨʁ ɤɚɪɰɢɧɨɦ ɛɭɛɪɟɝɚ ɤɨɞ ɝɨʁɚɡɧɢɯ, ɚ ɬɨ ɫɭ: ɬɤɢɜɧɚ ɯɢɩɨɤɫɢʁɚ, ɢɧɫɭɥɢɧɫɤɚ ɪɟɡɢɫɬɟɧɰɢʁɚ ɢ ɩɨɫɥɟɞɢɱɧɚ ɯɢɩɟɪɢɧɫɭɥɢɧɟɦɢʁɚ, ɩɨɪɟɦɟʄɟɧ ɟɧɞɨɤɪɢɧɢ ɦɢʂɟ ɢ ɩɪɨɞɭɤɰɢʁɚ ɚɞɢɩɨɤɢɧɚ, ɝɨʁɚɡɧɨɲʄɭ- ɢɧɞɭɤɨɜɚɧ ɢɧɮɥɚɦɚɬɨɪɧɢ ɨɞɝɨɜɨɪ, ɥɢɩɢɞɧɚ ɩɟɪɨɤɫɢɞɚɰɢʁɚ ɢ ɨɤɫɢɞɚɬɢɜɧɢ ɫɬɪɟɫ201. ɍɬɜɪђɟɧɨ ʁɟ ɞɚ ʁɟ ɜɢɫɨɤ BMI ʁɟ ɩɨɫɟɛɧɨ ɭɞɪɭɠɟɧ ɫɚ ɪɚɡɜɨʁɟɦ ɫɄȻ. ɋɬɭɞɢʁɚ Lowrance ɢ ɫɚɪ. ʁɟ ɩɨɤɚɡɚɥɚ ɞɚ ʁɟ ɡɚ ɫɜɚɤɢ 1 kg/m2ɩɨɜɟʄɚʃɚ BMI, ɫɬɨɩɚ ɨɛɨʂɟɜɚʃɚ ɨɞ ɫɄȻ ɫɟ ɩɨɜɟʄɚɜɚɥɚ ɡɚ 4%, ɬɟ ɫɭ ɝɨʁɚɡɧɢ ɩɚɰɢʁɟɧɬɢ ɢɦɚɥɢ 48% ɜɟʄɭ ɫɬɨɩɭ ɨɛɨʂɟɜɚʃɚ ɨɞ ɫɄȻ ɭ ɩɨɪɟђɟʃɭ ɫɚ ɨɧɢɦɚ ɤɨʁɢ ɫɭ ɢɦɚɥɢ BMI ɦɚʃɢ ɨɞ 30 kg/m2202. Donat ɢ ɫɚɪ. ɫɭ ɬɚɤɨђɟ ɩɨɤɚɡɚɥɢ ɞɚ ʁɟ BMI ≥30 kg/m2 ɛɢɨ ɩɨɜɟɡɚɧ ɫɚ ɩɨɜɟʄɚɧɢɦ ɞɢʁɚɝɧɨɫɬɢɤɨɜɚʃɟɦ ɫɄȻ ɤɨɞ ɩɚɰɢʁɟɧɚɬɚ ɥɟɱɟɧɢɯ ɨɩɟɪɚɬɢɜɧɨ ɡɛɨɝ ɬɭɦɨɪɚ ɛɭɛɪɟɝɚ, ɩɪɢ ɱɟɦɭ ʁɟ ɭ ɢɫɩɢɬɢɜɚɧɨʁ ɝɪɭɩɢ, 75% ɩɚɰɢʁɟɧɚɬɚ ɢɦɚɥɨ ɩɪɟɤɨɦɟɪɧɭ ɬɟɥɟɫɧɭ ɬɟɠɢɧɭ ɢɥɢ ɫɭ ɛɢɥɢ ɝɨʁɚɡɧɢ203.ɍ ɧɚɲɨʁ ɝɪɭɩɢ ɨɛɨɥɟɥɢɯ, 12 (29,27%) ɩɚɰɢʁɟɧɚɬɚ ɫɭ ɢɦɚɥɢ ɩɪɟɤɨɦɟɪɧɭ ɬɟɥɟɫɧɭ ɬɟɠɢɧɭ, ɚ 6 (14,63%) ɩɚɰɢʁɟɧɚɬɚ ɫɭ ɛɢɥɢ ɝɨʁɚɡɧɢ, ɞɨɤ ʁɟ ɜɟʄɢ ɛɪɨʁ ɨɛɨɥɟɥɢɯ, 23 (56.1%) ɢɦɚɨ ɧɨɪɦɚɥɧɭ ɬɟɥɟɫɧɭ ɬɟɠɢɧɭ. Ɇɟђɭ ɩɚɰɢʁɟɧɬɢɦɚ ɤɨʁɢ ɫɭ ɢɦɚɥɢ ɩɪɟɤɨɦɟɪɧɭ ɬɟɥɟɫɧɭ ɬɟɠɢɧɭ ɢɥɢ ɝɨʁɚɡɧɨɫɬ, ɭɤɭɩɧɨ 18 (43,9%), ɛɢɥɨ ʁɟ ɡɧɚɱɚʁɧɨ ɜɢɲɟ ɨɫɨɛɚ ɦɭɲɤɨɝ ɩɨɥɚ, ʃɢɯ 16 (88,9%) ɞɨɤ ɫɭ ɫɚɦɨ 2 (11,1%) ɛɢɥɟ ɨɫɨɛɟ ɠɟɧɫɤɨɝ ɩɨɥɚ. Ɇɨɠɟɦɨ ɡɚɤʂɭɱɢɬɢ ɢ ɞɚ ʁɟ ɭ ɧɚɲɨʁ ɝɪɭɩɢ ɨɛɨɥɟɥɢɯ ɡɧɚɱɚʁɧɨ ɦɚʃɢ ɩɪɨɰɟɧɚɬ ȾɂɋɄɍɋɂȳȺ 99 ɢɫɩɢɬɚɧɢɤɚ (43,9%) ɢɦɚɨ ɩɪɟɤɨɦɟɪɧɭ ɬɟɥɟɫɧɭ ɬɟɠɢɧɭ ɢɥɢ ɛɢɨ ɝɨʁɚɡɚɧ ɭ ɩɨɪɟђɟʃɭ ɫɚ ɫɬɭɞɢʁɨɦ Donat ɢ ɫɚɪ203. Ɂɚɤʂɭɱɚɤ ɞɚ ɯɢɩɟɪɬɟɧɡɢʁɚ ɩɨɜɟʄɚɜɚ ɪɢɡɢɤ ɨɞ ɩɨʁɚɜɟ ɄȻ ɩɨɬɜɪђɟɧ ʁɟ ɭ ɜɟʄɟɦ ɛɪɨʁɭ ɤɥɢɧɢɱɤɢɯ ɫɬɭɞɢʁɚ. ɋɬɭɞɢʁɚ ɫɩɪɨɜɟɞɟɧɚ ɭ ɒɜɟɞɫɤɨʁ ɧɚ ɩɨɩɭɥɚɰɢʁɢ ɨɞ 369.992 ɨɫɨɛɚ ɦɭɲɤɨɝ ɩɨɥɚ, ɩɨɤɚɡɚɥɚ ʁɟ ɞɢɪɟɤɬɧɭ ɩɨɜɟɡɚɧɨɫɬ ɢɡɦɟђɭ ɩɨɜɢɲɟɧɨɝ ɤɪɜɧɨɝ ɩɪɢɬɢɫɤɚ ɢ ɩɨɜɢɲɟɧɨɝ ɪɢɡɢɤɚ ɡɚ ɪɚɡɜɨʁ ɄȻ204. Colt ɢ ɫɚɪ. ɫɭ ɩɨɤɚɡɚɥɢ ɞɚ ɯɢɩɟɪɬɟɧɡɢʁɚ ɞɜɨɫɬɪɭɤɨ ɩɨɜɟʄɚɜɚ ɪɢɡɢɤ ɡɚ ɪɚɡɜɨʁ ɨɜɨɝ ɤɚɪɰɢɧɨɦɚ205. Ɍɚɱɚɧ ɦɟɯɚɧɢɡɚɦ ɩɨɜɟɡɚɧɨɫɬɢ ɯɢɩɟɪɬɟɧɡɢʁɟ ɢ ɄȻ ʁɟ ɧɟɞɨɜɨʂɧɨ ʁɚɫɚɧ, ɚɥɢ ɫɟ ɩɪɟɬɩɨɫɬɚɜʂɚ ɞɚ ɧɚɫɬɚʁɟ ɤɚɨ ɩɨɫɥɟɞɢɰɚ ɯɪɨɧɢɱɧɟ ɛɭɛɪɟɠɧɟ ɯɢɩɨɤɫɢʁɟ ɢ ɥɢɩɢɞɧɟ ɩɟɪɨɤɫɢɞɚɰɢʁɟ ɫɚ ɮɨɪɦɢɪɚʃɟɦ ɫɥɨɛɨɞɧɢɯ ɤɢɫɟɨɧɢɱɧɢɯ ɪɚɞɢɤɚɥɚ18. ɇɨɜɢʁɢ ɩɨɞɚɰɢ ɭɤɚɡɭʁɭ ɞɚ ɞɭɝɨɬɪɚʁɧɚ ɩɪɢɦɟɧɚ ɞɢɭɪɟɬɢɤɚ ɭ ɥɟɱɟʃɭ ɚɪɬɟɪɢʁɫɤɟ ɯɢɩɟɪɬɟɧɡɢʁɟ ɬɚɤɨђɟ ɩɨɜɟʄɚɜɚ ɪɢɡɢɤ ɡɚ ɪɚɡɜɨʁ ɨɜɨɝ ɤɚɪɰɢɧɨɦɚ, ɩɨɫɟɛɧɨ ɤɨɞ ɨɫɨɛɚ ɠɟɧɫɤɨɝ ɩɨɥɚ206. ɍ ɧɚɲɨʁ ɝɪɭɩɢ ɢɫɩɢɬɚɧɢɤɚ, ɤɨɞ ɜɟʄɢɧɟ ɨɛɨɥɟɥɢɯ, ɭɤɭɩɧɨ 23 (56,1%) ɛɢɥɚ ʁɟ ɩɪɢɫɭɬɧɚ ɚɪɬɟɪɢʁɫɤɚ ɯɢɩɟɪɬɟɧɡɢʁɚ. ɉɭɲɟʃɟ ɰɢɝɚɪɟɬɚ ɤɚɨ ɧɟɡɚɜɢɫɚɧ ɮɚɤɬɨɪ ɪɢɡɢɤɚ ɡɚ ɩɨʁɚɜɭ ɄȻ, ɩɨɜɟʄɚɜɚ ɪɢɡɢɤ ɡɚ ɨɤɨ 50% ɤɨɞ ɦɭɲɤɚɪɚɰɚ ɢ 20% ɤɨɞ ɠɟɧɚ ɩɭɲɚɱɚ ɭ ɨɞɧɨɫɭ ɧɚ ɨɫɨɛɟ ɤɨʁɟ ɧɢɤɚɞɚ ɧɢɫɭ ɛɢɥɢ ɩɭɲɚɱɢ. Ɇɟɯɚɧɢɡɚɦ ɤɨʁɢɦ ɩɭɲɟʃɟ ɰɢɝɚɪɟɬɚ ɩɨɜɟʄɚɜɚ ɪɢɡɢɤ ɨɞ ɨɜɟ ɜɪɫɬɟ ɤɚɪɰɢɧɨɦɚ ʁɟ ɯɪɨɧɢɱɧɚ ɬɤɢɜɧɚ ɯɢɩɨɤɫɢʁɚ ɭɞɪɭɠɟɧɚ ɫɚ ɟɫɤɩɨɡɢɰɢʁɨɦ ɭɝʂɟɧ ɦɨɧɨɤɫɢɞɭ ɢ ɡɚ ɩɭɲɟʃɟ ɜɟɡɚɧɚ ɫɬɚʃɚ ɤɚɨ ɲɬɨ ʁɟ ɨɛɫɬɪɭɤɬɢɜɧɚ ɛɨɥɟɫɬ ɩɥɭʄɚ207. ɍɬɜɪђɟɧɨ ʁɟ ɞɚ ɨɛɨɥɟɥɢ ɨɞ ɄȻ ɤɨʁɢ ɫɭ ɩɭɲɚɱɢ ɢɦɚʁɭ ɯɢɫɬɨɥɨɲɤɢ ɦɚɥɢɝɧɢʁɟ ɬɭɦɨɪɟ, ɥɨɲɢʁɟ ɩɪɟɠɢɜʂɚɜɚʃɟ ɢ ɩɨɜɟʄɚɧ ɪɢɡɢɤ ɨɞ ɦɭɬɚɰɢʁɟ p53, ɤɨʁɚ ɧɨɫɢ ɩɨɜɟʄɚɧ ɪɢɡɢɤ ɨɞ ɪɟɤɭɪɟɧɰɢʁɟ ɥɨɤɚɥɢɡɨɜɚɧɢɯ ɬɭɦɨɪɚ ɢ ɦɟɬɚɫɬɚɬɫɤɨɝ ɨɛɥɢɤɚ ɛɨɥɟɫɬɢ195. ɍ ɧɚɲɨʁ ɝɪɭɩɢ ɨɛɨɥɟɥɢɯ, ɩɭɲɚɱɚ ʁɟ ɛɢɥɚ ɜɢɲɟ, ɭɤɭɩɧɨ 25 (60.98%) ɭ ɨɞɧɨɫɭ ɧɚ ɨɛɨɥɟɥɟ ɤɨʁɢ ɧɢɤɚɞɚ ɧɢɫɭ ɛɢɥɢ ɩɭɲɚɱɢ, ɤɨʁɢɯ ʁɟ ɛɢɥɨ 16 (39.02%).ɉɚɰɢʁɟɧɬɢ ɫɚ ɄȻ ɦɨɝɭ ɫɟ ɤɥɢɧɢɱɤɢ ɩɪɟɡɟɧɬɨɜɚɬɢ ɪɚɡɥɢɱɢɬɢɦ, ɱɟɫɬɨ ɧɟɫɩɟɰɢɮɢɱɧɢɦ ɫɢɦɩɬɨɦɢɦɚ, ɩɪɢ ɱɟɦɭ ɜɟʄɢɧɚ ɨɫɬɚʁɟ ɚɫɢɦɩɬɨɦɚɬɫɤɚ ɞɨ ɫɬɚɞɢʁɭɦɚ ɭɡɧɚɩɪɟɞɨɜɚɥɟ ɛɨɥɟɫɬɢ.ɋɚɦɨ5-10% ɩɚɰɢʁɟɧɚɬɚ ɢɦɚ ɤɥɚɫɢɱɧɭ ȼɢɪɯɨɜʂɟɜɭ ɬɪɢʁɚɞɭ ɤɥɢɧɢɱɤɢɯ ɫɢɦɩɬɨɦɚ, ɤɨʁɭ ɱɢɧɟ: ɥɭɦɛɚɥɧɢ ɛɨɥ, ɦɚɤɪɨɫɤɨɩɫɤɚ ɯɟɦɚɬɭɪɢʁɚ ɢ ɩɚɥɩɚɛɢɥɧɚ ɬɭɦɨɪɫɤɚ ɦɚɫɚ76.ɇɚɫɭɩɪɨɬ ɬɨɦɟ, ɩɨɡɧɚɬɨ ʁɟ ɞɚ ʁɟ ɄȻ ʁɟɞɚɧ ɨɞ ɦɚɥɢɝɧɢɬɟɬɚ ɤɨʁɢ ɞɚʁɟ ɧɚʁɢɡɪɚɠɟɧɢʁɢ ɩɚɪɚɧɟɨɩɥɚɫɬɢɱɧɢ ɫɢɧɞɪɨɦ (ɉɇɋ) ɤɨʁɢ ɫɟ ɞɟɮɢɧɢɲɟ ɤɚɨ ɩɨɫɬɨʁɚʃɟ ɫɢɫɬɟɦɫɤɢɯ ɫɢɦɩɬɨɦɚ ɤɨɞ ɨɛɨɥɟɥɢɯ ɩɚɰɢʁɟɧɚɬɚ ɤɨʁɢ ɩɨɬɢɱɭ ɨɞ ɫɚɦɨɝ ɬɭɦɨɪɚ, ɚ ɧɢɫɭ ɩɨɫɥɟɞɢɰɚ ɦɟɬɚɫɬɚɬɫɤɢɯ ɩɪɨɦɟɧɚ, ɧɢɬɢ ɩɪɢɦɟʃɟɧɟ ɬɟɪɚɩɢʁɟ ɢ ɱɢʁɚ ɭɱɟɫɬɚɥɨɫɬ ɢɡɧɨɫɢ 10% ɞɨ 40%80. ȼɟʄɢɧɚ ɫɢɦɩɬɨɦɚ ʁɟ ɩɨɫɥɟɞɢɰɚ ɩɪɨɬɟɢɧɚ ɤɨʁɟ ɥɭɱɢ ɫɚɦ ɬɭɦɨɪ ɢɥɢ ɫɟɤɭɧɞɚɪɧɨ ɢɦɭɧɫɤɢ ɫɢɫɬɟɦ, ɚ ɫɦɚɬɪɚ ɫɟ ɞɚ ɭ ɨɫɧɨɜɢ ʃɟɝɨɜɨɝ ɧɚɫɬɚɧɤɚ ɫɬɨʁɢ ɩɨɜɟʄɚɧɨ ɥɭɱɟʃɟ ɰɢɬɨɤɢɧɚ, ɤɚɨ ɲɬɨ ʁɟ IL-681. ɍ ɧɚɲɨʁ ɝɪɭɩɢ ɨɛɨɥɟɥɢɯ ɢɫɩɢɬɢɜɚɧɨ ʁɟ ɩɨɫɬɨʁɚʃɟ ɫɥɟɞɟʄɢɯ ɫɢɦɩɬɨɦɚ ɉɇɋ: ɝɭɛɢɬɚɤ ɭ ɬɟɥɟɫɧɨʁ ɦɚɫɢ, ɥɭɦɛɚɥɧɢ ɛɨɥ, ɦɚɤɪɨɫɤɨɩɫɤɚ ɯɟɦɚɬɭɪɢʁɚ ɢ ɩɨɜɢɲɟɧɚ ɬɟɥɟɫɧɚ ɬɟɦɩɟɪɚɬɚɭɪɚ. Ȼɚɪ ʁɟɞɚɧ ɨɞ ɢɫɩɢɬɢɜɚɧɢɯ ɫɢɦɩɬɨɦɚ ɛɢɨ ʁɟ ɩɪɢɫɭɬɚɧ ɤɨɞ 10 ɩɚɰɢʁɟɧɚɬɚ, ɲɬɨ ɱɢɧɢ 24,39% ɨɛɨɥɟɥɚ, ɞɨɤ 31 ɩɚɰɢʁɟɧɬ ɢɥɢ 75,61% ɧɢʁɟ ɢɦɚɨ ɧɢʁɟɞɚɧ ɫɢɦɩɬɨɦ ɩɚɪɚɧɟɨɩɥɚɫɬɢɱɤɨɝ ɫɢɧɞɪɨɦɚ. ɇɚɲɢ ɪɟɡɭɥɬɚɬɢ ɫɟ ɩɨɤɥɚɩɚʁɭ ɫɚ ɪɟɡɭɥɬɚɬɢɦɚ ɫɬɭɞɢʁɟ Schips ɢ ɫɚɪ. ɭ ɤɨʁɨʁ ʁɟ ɩɪɢɛɥɢɠɧɨ ɢɫɬɢ ɩɪɨɰɟɧɚɬ ɨɛɨɥɟɥɢɯ, 20,8%, ɢɦɚɨ ɫɢɦɩɬɨɦɚɬɫɤɭ ɛɨɥɟɫɬ208. ɇɚɫɭɩɪɨɬ ɬɨɦɟ, ɭ ɫɬɭɞɢʁɢ Ding ɢ ɫɚɪ., ɨɞ 1.512 ɩɚɰɢʁɟɧɚɬɚ ɤɨɞ 1.028 (67.98%) ɛɢɨ ʁɟ ɩɪɢɫɭɬɚɧ ɛɚɪ ʁɟɞɚɧ ɫɢɦɩɬɨɦ ɉɇɋ, ɲɬɨ ʁɟ ɡɧɚɱɚʁɧɨ ɜɢɲɟ209. Ƚɭɛɢɬɚɤ ɭ ɬɟɥɟɫɧɨʁ ɦɚɫɢ ɢɦɚɥɚ ɫɭ ɫɚɦɨ 2 ɩɚɰɢʁɟɧɬɚ, ɲɬɨ ɱɢɧɢ 4,88% ɨɞ ɭɤɭɩɧɨɝ ɛɪɨʁɚ ɨɛɨɥɟɥɢɯ. Ɉɛɚ ɩɚɰɢʁɟɧɬɚ ɫɭ ɢɦɚɥɚ ɬɭɦɨɪɟ ɞɢɦɟɧɡɢʁɚ ɩɪɟɤɨ 10 cm, ɜɢɫɨɤɨɝ ɯɢɫɬɨɥɨɲɤɨɝ ɝɪɚɞɭɫɚ ɩɨ ȾɂɋɄɍɋɂȳȺ 100 Fuhrman-ɭ (G3 ɢ G4), ɤɨɞ ʁɟɞɧɨɝ ɩɚɰɢʁɟɧɬɚ ʁɟ ɛɢɥɚ ɩɪɢɫɭɬɧɚ ɫɚɪɤɨɦɚɬɨɢɞɧɚ ɢ ɪɚɛɞɨɢɞɧɚ ɬɪɚɧɫɮɨɪɦɚɰɢʁɚ ɢ ɨɛɚ ɩɚɰɢʁɟɧɬɚ ɫɭ ɢɦɚɥɚ ɬɪɟʄɢ ɫɬɚɞɢʁɭɦ ɛɨɥɟɫɬɢ ɩɨ TNM ɤɥɚɫɢɮɢɤɚɰɢʁɢ. ɇɚɲɢ ɪɟɡɭɥɬɚɬɢ ɫɟ ɩɨɤɥɚɩɚʁɭ ɫɚ ɫɬɭɞɢʁɨɦ Takure ɢ ɫɚɪ. ɭ ɤɨʁɨʁ ʁɟ ɨɞ 69 ɢɫɩɢɬɢɜɚɧɢɯ ɩɚɰɢʁɟɧɚɬɚ, 4% ɢɦɚɥɨ ɝɭɛɢɬɚɤ ɭ ɬɟɥɟɫɧɨʁ ɦɚɫɢ210. ɍ ɫɬɭɞɢʁɢ Yap ɢ ɫɚɪ. ɝɭɛɢɬɚɤ ɭ ɬɟɥɟɫɧɨʁ ɦɚɫɢ ɢɦɚɨ ʁɟ ɡɧɚɱɚʁɧɨ ɜɟʄɢ ɩɪɨɰɟɧɚɬ ɨɛɨɥɟɥɢɯ, 39,7%211. ɋɥɢɱɧɟ ɪɟɡɭɥɬɚɬɟ ɨɛʁɚɜɢɥɢ ɫɭ Stenman ɢ ɫɚɪ., ɭ ɱɢʁɨʁ ɫɬɭɞɢʁɢ ʁɟ 33% ɩɚɰɢʁɟɧɚɬɚ ɢɦɚɥɨ ɨɜɚʁ ɫɢɦɩɬɨɦ ɛɨɥɟɫɬɢ. ɍ ɜɟɥɢɤɨʁ ɪɟɬɪɨɫɩɟɤɬɢɜɧɨʁ ɫɬɭɞɢʁɢ ɧɚ 1046 ɩɚɰɢʁɟɧɚɬɚ, ɝɭɛɢɬɚɤ ɭ ɬɟɥɟɫɧɨʁ ɦɚɫɢ ʁɟ ɛɢɨ ɩɪɢɫɭɬɚɧ ɤɨɞ 22,9% ɨɛɨɥɟɥɢɯ. Ʌɭɦɛɚɥɧɢ ɛɨɥ ʁɟ ɛɢɨ ɩɪɢɫɭɬɚɧ ɤɨɞ 7 ɩɚɰɢʁɟɧɚɬɚ ɬʁ. 17,01% ɨɛɨɥɟɥɢɯ212. ɍ ɫɬɭɞɢʁɢ Takure ɢ ɫɚɪ. ɨɜɚʁ ɫɢɦɩɬɨɦ ʁɟ ɛɢɨ ɩɪɢɫɭɬɚɧ ɤɨɞ 29% ɨɛɨɥɟɥɢɯ210. ɉɨɜɢɲɟɧɚ ɬɟɥɟɫɧɚ ɬɟɦɩɟɪɚɬɭɪɚ ɩɪɢɫɭɬɧɚ ʁɟ ɤɨɞ ɨɤɨ 20% ɩɚɰɢʁɟɧɚɬɚ ɢ ɨɛɢɱɧɨ ʁɟ ɢɧɬɟɪɦɢɬɟɧɬɧɚ. ɂɧɬɟɪɥɟɭɤɢɧ 6 (IL-6) ʁɟ ɩɪɨɭɱɚɜɚɧ ɤɚɨ ɦɨɝɭʄɢ ɩɢɪɨɝɟɧ ɤɨɞ ɨɛɨɥɟɥɢɯ ɨɞ ɄȻ, ɩɚ ʁɟ ɬɚɤɨ ɭ ɫɬɭɞɢʁɢ Tsukamotɚ ɢ ɫɚɪ., ɨɞ ɭɤɭɩɧɨ 71 ɛɨɥɟɫɧɢɤɚ ɫɚ ɞɢʁɚɝɧɨɡɨɦ ɄȻ, ɤɨɞ 18 ʁɟ ɞɨɤɚɡɚɧɚ ɩɨɜɢɲɟɧɚ ɤɨɧɰɟɧɬɪɚɰɢʁɚ IL-6, ɚ 78% ɨɧɢɯ ɫɚ ɩɨɜɢɲɟɧɢɦ ɧɢɜɨɨɦ IL-6 ʁɟ ɢɦɚɥɨ ɩɨɜɢɲɟɧɭ ɬɟɦɩɟɪɚɬɭɪɭ95. ɍ ɫɬɭɞɢʁɢ ɦɚɥɟɡɢʁɫɤɢɯ ɚɭɬɨɪɚ ɩɨɜɢɲɟɧɚ ɬɟɥɟɫɧɚ ɬɟɦɩɟɪɚɬɭɪɚ ɛɢɥɚ ʁɟ ɩɪɢɫɭɬɧɚ ɤɨɞ 13,2% ɩɚɰɢʁɟɧɚɬɚ211, ɞɨɤ ʁɟ ɭ ɫɬɭɞɢʁɢ Ding ɢ ɫɚɪ. ɨɜɚʁ ɫɢɦɩɬɨɦ ɉɇɋ ɛɢɨ ɩɪɢɫɭɬɚɧ ɤɨɞ 23,9%, ɨɞɧɨɫɧɨ 21,4% ɨɛɨɥɟɥɢɯ213,209. ɍ ɧɚɲɨʁ ɝɪɭɩɢ ɨɛɨɥɟɥɢɯ ɧɢʁɟɞɚɧ ɩɚɰɢʁɟɧɬ ɧɢʁɟ ɢɦɚɨ ɨɜɚʁ ɫɢɦɩɬɨɦ ɛɨɥɟɫɬɢ. Ɇɚɤɪɨɫɤɨɩɫɤɚ ɯɟɦɚɬɭɪɢʁɚ ɫɟ ʁɚɜʂɚ ɭ ɫɥɭɱɚʁɟɜɢɦɚ ɬɭɦɨɪɫɤɟ ɢɧɜɚɡɢʁɟ ɫɚɛɢɪɧɨɝ ɫɢɫɬɟɦɚ ɛɭɛɪɟɝɚ ɢ ɭ ɧɚɲɨʁ ɝɪɭɩɢ ɨɛɨɥɟɥɢɯ ʁɟ ɛɢɥɚ ɩɪɢɫɭɬɧɚ ɤɨɞ 7 ɩɚɰɢʁɟɧɚɬɚ, ɲɬɨ ɱɢɧɢ 17,01% ɨɛɨɥɟɥɢɯ. Ɉɞ ɩɚɰɢʁɟɧɚɬɚ ɫɚ ɨɜɢɦ ɫɢɦɩɬɨɦɨɦ, ʃɢɯ 6 ʁɟ ɢɦɚɥɨ ɬɭɦɨɪɟ ɜɟʄɟ ɨɞ 7 cm, ɚ ɫɚɦɨ 1 ɩɚɰɢʁɟɧɬ ʁɟ ɢɦɚɨ ɬɭɦɨɪ ɦɚʃɢ ɨɞ 4 cm ɤɨʁɢ ʁɟ ɜɪɲɢɨ ɢɧɜɚɡɢʁɭ ɫɚɛɢɪɧɨɝ ɫɢɫɬɟɦɚ ɛɭɛɪɟɝɚ. Ɉɜɚʁ ɫɢɦɩɬɨɦ ɫɟ ʁɚɜʂɚ ɤɨɞ ɨɤɨ 35% ɨɛɨɥɟɥɢɯ ɲɬɨ ʁɟ ɩɨɬɜɪђɟɧɨ ɢ ɭ ɫɬɭɞɢʁɢ Yap ɢ ɫɚɪ211. ɍ ɫɬɭɞɢʁɢ Takure ɢ ɫɚɪ. ɨɜɚʁ ɫɢɦɩɬɨɦ ʁɟ ɛɢɨ ɩɪɢɫɭɬɚɧ ɤɨɞ 18,8% ɨɛɨɥɟɥɢɯ210. ɍ ɧɚɲɨʁ ɫɬɭɞɢʁɢ ɨɜɚʁ ɫɢɦɩɬɨɦ ɫɟ ʁɚɜɢɨ ɭ ɡɧɚɱɚʁɧɨ ɦɚʃɟɦ ɩɪɨɰɟɧɬɭ. Ɇɨɠɟ ɫɟ ɡɚɤʂɭɱɢɬɢ ɞɚ ʁɟ ɦɚʃɚ ɢɧɰɢɞɟɧɰɚ ɢɫɩɢɬɢɜɚɧɢɯ ɫɢɦɩɬɨɦɚ ɉɇɋ ɧɚʁɜɟɪɨɜɚɬɧɢʁɟ ɩɨɫɥɟɞɢɰɚ ɪɟɥɚɬɢɜɧɨ ɦɚɥɨɝ ɛɪɨʁɚ ɢɫɩɢɬɚɧɢɤɚ ɭ ɧɚɲɨʁ ɫɬɭɞɢʁɢ. ɏɢɩɟɪɤɚɥɰɟɦɢʁɚ ʁɟ ɧɚʁɱɟɲʄɚ ɩɚɪɚɧɟɨɩɥɚɫɬɢɱɧɚ ɦɚɧɢɮɟɫɬɚɰɢʁɚ ɄȻ, ɤɨʁɚ ɫɟ ʁɚɜʂɚ ɤɨɞ 13- 20% ɨɛɨɥɟɥɢɯ214. ɉɪɢɫɭɫɬɜɨ ɯɢɩɟɪɤɚɥɰɟɦɢʁɟ ɤɨɪɟɥɢɪɚ ɫɚ VEGF ɟɤɫɩɪɟɫɢʁɨɦ, ɚ ɤɨɞ ɦɟɬɚɫɬɚɬɫɤɟ ɛɨɥɟɫɬɢ ɫɚ ɥɨɲɨɦ ɩɪɨɝɧɨɡɨɦ209, 215. ɍ ɫɬɭɞɢʁɢ Ding ɢ ɫɚɪ. ɯɢɩɟɪɤɚɥɰɟɦɢʁɚ ʁɟ ɛɢɥɚ ɩɪɢɫɭɬɧɚ ɤɨɞ 6,7% ɨɛɨɥɟɥɢɯ ɨɞ ɫɄȻ213. ɍ ɫɬɭɞɢʁɢ ɞɪɭɝɢɯ ɚɭɬɨɪɚ ɯɢɩɟɪɤɚɥɰɟɦɢʁɚ ʁɟ ɛɢɥɚ ɩɪɢɫɭɬɧɚ ɤɨɞ 11% ɨɛɨɥɟɥɢɯ211.ɍ ɧɚɲɨʁ ɝɪɭɩɢ ɨɛɨɥɟɥɢɯ ɧɢʁɟɞɚɧ ɩɚɰɢʁɟɧɬ ɧɢʁɟ ɢɦɚɨ ɯɢɩɟɪɤɚɥɰɟɦɢʁɭ. Ⱥɧɚɟɦɢʁɚ ɤɚɨ ɡɧɚɤ ɉɇɋ ʁɟ ɩɪɢɫɭɬɧɚ ɤɨɞ ɨɤɨ 20% ɩɚɰɢʁɟɧɚɬɚ ɫɚ ɄȻ ɢ ɩɨ ɩɪɚɜɢɥɭ ʁɟ ɧɨɪɦɨɰɢɬɧɚ ɢ ɧɨɪɦɨɯɪɨɦɧɚ. Ʌɨɲ ɧɭɬɪɢɬɢɜɧɢ ɫɬɚɬɭɫ ɢ ɩɪɢɫɭɫɬɜɨ ɯɪɨɧɢɱɧɟ ɛɨɥɟɫɬɢ ɫɭ ɞɜɚ ɝɥɚɜɧɚ ɪɚɡɥɨɝɚ ɡɚ ɧɚɫɬɚɧɚɤ ɚɧɟɦɢʁɟ, ɦɚɞɚ ɫɟ ɫɦɚɬɪɚ ɞɚ ɨɧɚ ɦɨɠɟ ɧɚɫɬɚɬɢ ɫɟɤɭɧɞɚɪɧɨ ɤɚɨ ɩɨɫɥɟɞɢɰɚ ɞɟɩɪɟɫɢʁɟ ɤɨɲɬɚɧɟ ɫɪɠɢ ɢɥɢ ɤɚɨ ɩɨɫɥɟɞɢɰɚ ɬɭɦɨɪɫɤɟ ɩɪɨɞɭɤɰɢʁɟ ɝɜɨɠђɟ-ɜɟɡɭʁɭʄɢɯ ɩɪɨɬɟɢɧɚ, ɤɚɨ ɲɬɨ ɫɭ ɮɟɪɢɬɢɧ ɢ ɥɚɤɬɨɮɟɪɢɧ216. ɇɟ ɩɨɫɬɨʁɢ ɩɨɜɟɡɚɧɨɫɬ ɢɡɦɟђɭ ɩɪɟɨɩɟɪɚɬɢɜɧɟ ɚɧɟɦɢʁɟ ɢ ɫɬɚɞɢʁɭɦɚ ɛɨɥɟɫɬɢ. ɍ ɧɚɲɨʁ ɫɬɭɞɢʁɢ ɚɧɟɦɢʁɚ ʁɟ ɛɢɥɚ ɩɪɢɫɭɬɧɚ ɤɨɞ 13 ɢɥɢ 31,7% ɨɛɨɥɟɥɢɯ, ɲɬɨ ʁɟ ɫɤɨɪɨ ɢɧɞɟɧɬɢɱɧɨ ɪɟɡɭɥɬɚɬɢɦɚ ɫɬɭɞɢʁɚ ɞɪɭɝɢɯ ɚɭɬɨɪɚ, ɤɨɞ ɤɨʁɢɯ ʁɟ ɨɜɚʁ ɡɧɚɤ ɉɇɋ ɛɢɨ ɩɪɢɫɭɬɚɧ ɤɨɞ 31.2%, ɨɞɧɨɫɧɨ 31,8% ɨɛɨɥɟɥɢɯ213, 209. ȾɂɋɄɍɋɂȳȺ 101 5.2. ȼɪɫɬɚ ɨɩɟɪɚɬɢɜɧɨɝ ɥɟɱɟʃɚ ɢ ɩɚɬɨɯɢɫɬɨɥɨɲɤɟ ɤɚɪɚɤɬɟɪɢɫɬɢɤɟ ɬɭɦɨɪɚ ɭ ɝɪɭɩɢ ɨɛɨɥɟɥɢɯ ɨɞ ɤɚɪɰɢɧɨɦɚ ɫɜɟɬɥɢɯ ʄɟɥɢʁɚ ɛɭɛɪɟɝɚ Ⱦɟɰɟɧɢʁɚɦɚ ʁɟ ɪɚɞɢɤɚɥɧɚ ɧɟɮɪɟɤɬɨɦɢʁɚ (Ɋɇ) ɛɢɥɚ ɡɥɚɬɧɢ ɫɬɚɧɞɚɪɞ ɭ ɨɩɟɪɚɬɢɜɧɨɦ ɥɟɱɟʃɭ ɬɭɦɨɪɚ ɛɭɛɪɟɝɚ. Ɉɫɚɦɞɟɫɟɬɢɯ ɝɨɞɢɧɚ ɩɪɨɲɥɨɝ ɜɟɤɚ ɨɜɚʁ ɩɪɢɫɬɭɩ ʁɟ ɢɡɦɟʃɟɧ ɩɪɢɦɟɧɨɦ ɩɚɪɰɢʁɚɥɧɟ ɧɟɮɪɟɤɬɨɦɢʁɟ (ɉɇ) ɤɨɞ ɩɚɰɢʁɟɧɚɬɚ ɫɚ ɫɨɥɢɬɚɪɧɢɦ ɛɭɛɪɟɝɨɦ, ɚ ɨɞ 2007. ɝɨɞɢɧɟ ɨɧɚ ɩɨɫɬɚʁɟ ɫɬɚɧɞɚɪɞ ɭ ɥɟɱɟʃɭ ɬɭɦɨɪɫɤɢɯ ɩɪɨɦɟɧɚ ɦɚʃɢɯ ɨɞ 4 cm ɤɨɞ ɩɚɰɢʁɟɧɚɬɚ ɫɚ ɡɞɪɚɜɢɦ ɤɨɧɬɪɚɥɚɬɟɪɚɥɧɢɦ ɛɭɛɪɟɝɨɦ (ɟɥɟɤɬɢɜɧɚ ɢɧɞɢɤɚɰɢʁɚ)49. Ɋɚɡɥɨɝ ɨɜɚɤɜɨɝ ɩɪɢɫɬɭɩɚ ʁɟ ɩɨɬɪɟɛɚ ɡɚ ɲɬɨ ɛɨʂɢɦ ɨɱɭɜɚʃɟɦ ɛɭɛɪɟɠɧɟ ɮɭɧɤɰɢʁɟ, ɬʁ. ɫɩɪɟɱɚɜɚʃɟɦ ɪɚɡɜɨʁɚ ɯɪɨɧɢɱɧɟ ɛɭɛɪɟɠɧɟ ɢɧɫɭɮɢɰɢʁɟɧɰɢʁɟ. Ⱦɨɤɚɡɚɧɨ ʁɟ ɞɚ ɧɚɫɬɚɧɚɤ ɚɤɭɬɧɟ ɛɭɛɪɟɠɧɟ ɢɧɫɭɮɢɰɢʁɟɧɰɢʁɟ ɧɚɤɨɧ Ɋɇ ɩɪɟɞɫɬɚɜʂɚ ɫɧɚɠɚɧ ɮɚɤɬɨɪ ɪɢɡɢɤɚ ɡɚ ɪɚɡɜɨʁ ɯɪɨɧɢɱɧɟ ɛɭɛɪɟɠɧɟ ɢɧɫɭɮɢɰɢʁɟɧɰɢʁɟ217. ɋɧɢɠɟɧɚ ɛɭɛɪɟɠɧɚ ɮɭɧɤɰɢʁɚ ɢɫɤɚɡɚɧɚ ɩɪɟɤɨ ɤɥɢɪɟɧɫɚ ɤɪɟɚɬɢɧɢɧɚ ɤɨʁɢ ʁɟ ɦɚʃɢ ɨɞ 60 ml/min ɨɩɢɫɚɧɚ ʁɟ ɤɨɞ 45-70% ɩɚɰɢʁɟɧɚɬɚ ɧɚɤɨɧ Ɋɇ, ɞɨɤ ʁɟ ɩɨɬɪɟɛɚ ɡɚ ɡɚɦɟɧɭ ɛɭɛɪɟɠɧɟ ɮɭɧɤɰɢʁɟ ɧɟɤɢɦ ɨɞ ɨɛɥɢɤɚ ɞɢʁɚɥɢɡɟ ɤɨɞ ɨɜɢɯ ɛɨɥɟɫɧɢɤɚ ɢɡɧɨɫɢɥɚ 2- 6,2%218. Ɋɟɡɭɥɬɚɬɢ ɞɨɫɚɞɚɲʃɢɯ ɢɫɩɢɬɢɜɚʃɚ ɭɤɚɡɭʁɭ ɞɚ ɪɚɡɜɨʁ ɯɪɨɧɢɱɧɟ ɛɭɛɪɟɠɧɟ ɢɧɫɭɮɢɰɢʁɟɧɰɢʁɟ ɩɨɜɟʄɚɜɚ ɤɚɪɞɢɨɜɚɫɤɭɥɚɪɧɢ ɦɨɪɛɢɞɢɬɟɬ ɢ ɫɦɚʃɭʁɟ ɨɱɟɤɢɜɚɧɢ ɠɢɜɨɬɧɢ ɜɟɤ, ɱɢɦɟ ɫɟ ɩɪɟɞ ɯɢɪɭɪɝɟ ɩɨɫɬɚɜʂɚ ɡɚɯɬɟɜ ɡɚ ɲɬɨ ɜɟʄɨɦ ɩɪɟɡɟɪɜɚɰɢʁɨɦ ɛɭɛɪɟɠɧɨɝ ɩɚɪɟɧɯɢɦɚ. Matsushita ɢ ɫɚɪ. ɫɭ ɦɟɬɚɚɧɚɥɢɡɨɦ 21 ɫɬɭɞɢʁɟ ɤɨʁɚ ʁɟ ɨɛɭɯɜɚɬɢɥɚ ɩɪɟɤɨ ɦɢɥɢɨɧ ɢɫɩɢɬɚɧɢɤɚ, ɩɨɤɚɡɚɥɢ ɞɚ ɫɧɢɠɟɧɚ ɛɭɛɪɟɠɧɚ ɮɭɧɤɰɢʁɚ ɩɪɟɞɫɬɚɜʂɚ ɧɟɡɚɜɢɫɚɧ ɩɪɟɞɢɤɬɨɪ ɭɤɭɩɧɨɝ ɢ ɤɚɪɞɢɨɜɚɫɤɭɥɚɪɧɨɝ ɦɨɪɬɚɥɢɬɟɬɚ219. ȳɟɞɢɧɚ ɞɨ ɫɚɞɚ ɦɭɥɬɢɰɟɧɬɪɢɱɧɚ ɪɚɧɞɨɦɢɡɨɜɚɧɚ ɫɬɭɞɢʁɚ ɫɩɪɨɜɟɞɟɧɚ ɧɚ 547 ɩɚɰɢʁɟɧɚɬɚ ɥɟɱɟɧɢɯ ɩɪɢɦɟɧɨɦ ɉɇ (268 ɩɚɰɢʁɟɧɚɬɚ) ɢ Ɋɇ (273 ɩɚɰɢʁɟɧɬɚ), ɩɨɤɚɡɚɥɚ ʁɟ ɞɚ ɉɇ ɫɦɚʃɭʁɟ ɢɧɰɢɞɟɧɰɭ ɭɦɟɪɟɧɟ ɛɭɛɪɟɠɧɟ ɢɧɫɭɮɢɰɢʁɟɧɰɢʁɟ, ɞɨɤ ʁɟ ɢɧɰɢɞɟɧɰɚ ɭɡɧɚɩɪɟɞɨɜɚɥɢɯ ɫɬɚɞɢʁɭɦɚ ɛɭɛɪɟɠɧɟ ɢɧɫɭɮɢɰɢʁɟɧɰɢʁɟ ɛɢɥɚ ɜɟɨɦɚ ɫɥɢɱɧɚ ɢɥɢ ɫɤɨɪɨ ɢɧɞɟɧɬɢɱɧɚ. Ɇɟђɭɬɢɦ, ɩɨɜɨʂɚɧ ɟɮɟɤɚɬ ɉɇ ɧɚ ɛɭɛɪɟɠɧɭ ɮɭɧɤɰɢʁɭ ɧɢʁɟ ɪɟɡɭɥɬɨɜɚɨ ɭ ɩɨɛɨʂɲɚʃɭ ɩɪɟɠɢɜʂɚɜɚʃɚ ɭ ɩɨɫɦɚɬɪɚɧɨʁ ɝɪɭɩɢ ɩɚɰɢʁɟɧɚɬɚ ɭ ɩɟɪɢɨɞɭ ɩɪɚʄɟʃɚ ɤɨʁɢ ʁɟ ɢɡɧɨɫɢɨ 9,3 ɝɨɞɢɧɟ220. ɋɦɚɬɪɚ ɫɟ ɞɚ ɚɤɬɭɟɥɧɨ ɭ ɋȺȾ ɢɦɚ ɜɢɲɟ ɨɞ 300.000 ɩɚɰɢʁɟɧɚɬɚ ɤɨʁɢ ɫɟ ɩɪɚɬɟ ɧɚɤɨɧ ɥɟɱɟʃɚ ɤɚɪɰɢɧɨɦɚ ɛɭɛɪɟɝɚ. ɋ ɨɛɡɢɪɨɦ ɧɚ ɫɬɚɪɢʁɭ ɠɢɜɨɬɧɭ ɞɨɛ ɢ ɱɟɫɬɨ ɩɪɢɫɭɬɧɟ ɤɨɨɦɨɪɛɢɞɢɬɟɬɟ ɭ ɨɜɨʁ ɝɪɭɩɢ ɩɚɰɢʁɟɧɚɬɚ ɤɚɨ ɲɬɨ ɫɭ ɞɢʁɚɛɟɬɟɫ ɢ ɚɪɬɟɪɢʁɫɤɚ ɯɢɩɟɪɬɟɧɡɢʁɚ, ɩɨɫɟɛɧɚ ɩɚɠʃɚ ʁɟ ɭɫɦɟɪɟɧɚ ɧɚ ɨɱɭɜɚʃɟ ɛɭɛɪɟɠɧɟ ɮɭɧɤɰɢʁɟ ɤɚɨ ɢ ɥɟɱɟʃɟ ɜɟʄ ɪɚɡɜɢʁɟɧɟ ɯɪɨɧɢɱɧɟ ɛɭɛɪɟɠɧɟ ɢɧɫɭɮɢɰɢʁɟɧɰɢʁɟ, ɭ ɤɨʁɨʁ ɩɨɫɟɛɧɭ ɭɥɨɝɭ ɢɦɚ ɧɟɮɪɨɥɨɝ221. ȼɟɥɢɱɢɧɚ ɬɭɦɨɪɚ ɫɟ ɜɢɲɟ ɧɟ ɫɦɚɬɪɚ ɨɝɪɚɧɢɱɚɜɚʁɭʄɢɦ ɮɚɤɬɨɪɨɦ ɡɚ ɉɇ, ɬɟ ɫɟ ɨɜɚʁ ɜɢɞ ɯɢɪɭɪɲɤɨɝ ɥɟɱɟʃɚ ɩɪɟɞɥɚɠɟ ɤɚɞ ɝɨɞ ʁɟ ɬɨ ɦɨɝɭʄɟ ɢ ɢɡɜɨɞʂɢɜɨ164. Weight ɢ ɫɚɪ. ɫɭ ɭ ɫɬɭɞɢʁɢ ɫɩɪɨɜɟɞɟɧɨʁ ɧɚ 510 ɩɚɰɢʁɟɧɚɬɚ ɥɟɱɟɧɢɯ ɉɇ (212 ɩɚɰɢʁɟɧɚɬɚ) ɢ Ɋɇ (298 ɩɚɰɢʁɟɧɚɬɚ) ɡɛɨɝ ɬɭɦɨɪɫɤɟ ɩɪɨɦɟɧɟ ɞɢɦɟɧɡɢʁɚ 4,1-7 cm,ɩɨɤɚɡɚɥɢ ɞɚ ɫɟ ɩɪɢɦɟɧɨɦ ɉɇ ɩɨɫɬɢɠɟ ɢɫɬɚ ɤɨɧɬɪɨɥɚ ɛɨɥɟɫɬɢ, ɭɡ ɡɧɚɱɚʁɧɨ ɛɨʂɟ ɭɤɭɩɧɨ ɩɪɟɠɢɜʂɚɜɚʃɟ222.Milonas ɢ ɫɚɪ. ɫɭ ɧɚ ɨɫɧɨɜɭ ɪɟɡɭɥɬɚɬɚ ɫɬɭɞɢʁɟ ɫɩɪɨɜɟɞɟɧɟ ɧɚ 354 ɩɚɰɢʁɟɧɬɚ ɥɟɱɟɧɚ ɨɩɟɪɚɬɢɜɧɨ ɡɛɨɝ ɬɭɦɨɪɫɤɟ ɩɪɨɦɟɧɟ ɞɢɦɟɧɡɢʁɚ 4-7cm, ɞɨɲɥɢ ɞɨ ɡɚɤʂɭɱɤɚ ɞɚ ɉɇ ɩɪɟɞɫɬɚɜʂɚ ɦɟɬɨɞɭ ɢɡɛɨɪɚ ɡɚ ɥɟɱɟʃɟ ɨɜɢɯ ɬɭɦɨɪɚ223. Roos ɢ ɫɚɪ. ɫɭ ɭ ɫɜɨʁɨʁ ɫɬɭɞɢʁɢ ɩɨɤɚɡɚɥɢ ɞɚ ɨɩɟɪɚɬɢɜɧɨ ɥɟɱɟʃɟ ɬɭɦɨɪɚ ɞɢɦɟɧɡɢʁɚ ɜɟʄɢɯ ɨɞ 4 cm ɩɪɢɦɟɧɨɦ ɟɥɟɤɬɢɜɧɟ ɉɇ ɩɪɟɞɫɬɚɜʂɚ ɦɟɬɨɞɭ ɢɡɛɨɪɚ ɤɚɞ ɝɨɞ ʁɟ ɬɨ ɬɟɯɧɢɱɤɢ ɢɡɜɨɞʂɢɜɨ ɡɛɨɝ ɫɢɝɧɢɮɢɤɚɧɬɧɨ ɧɢɠɟɝ ɪɢɡɢɤɚ ɡɚ ɪɚɡɜɨʁ ɯɪɨɧɢɱɧɟ ɛɭɛɪɟɠɧɟ ȾɂɋɄɍɋɂȳȺ 102 ɢɧɫɭɮɢɰɢʁɟɧɰɢʁɟ224. Becker ɢ ɫɚɪ. ɫɭ ɭ ɪɟɬɪɨɫɩɟɤɬɢɜɧɨʁ ɫɬɭɞɢʁɢ ɫɩɪɨɜɟɞɟɧɨʁ ɧɚ 91 ɩɚɰɢʁɟɧɬɭ ɫɚ ɬɭɦɨɪɫɤɨɦ ɩɪɨɦɟɧɨɦ ɞɢɦɟɧɡɢʁɚ ɜɟʄɢɯ ɨɞ 7 cm ɤɨʁɢ ɫɭ ɥɟɱɟɧɢ ɩɪɢɦɟɧɨɦ ɉɇ, ɩɨɤɚɡɚɥɢ ɞɚ ɩɨɫɬɨʁɢ ɩɪɢɯɜɚɬʂɢɜɚ ɫɬɨɩɚ ɤɨɦɩɥɢɤɚɰɢʁɚ ɢ ɤɨɦɩɚɪɚɛɢɥɧɨ ɨɧɤɨɥɨɲɤɨ ɩɪɟɠɢɜʂɚɜɚʃɟ ɭ ɩɨɪɟђɟʃɭ ɫɚ ɩɚɰɢʁɟɧɬɢɦɚ ɥɟɱɟɧɢɦ ɩɪɢɦɟɧɨɦ Ɋɇ164. Li ɢ ɫɚɪ. ɫɭ ɦɟɬɚ- ɚɧɚɥɢɡɨɦ 10 ɫɬɭɞɢʁɚ ɧɚ ɭɤɭɩɧɨ 10.174 ɩɚɰɢʁɟɧɬɚ ɫɚ ɤɚɪɰɢɧɨɦɨɦ ɛɭɛɪɟɝɚ ɩɨɤɚɡɚɥɢ ɞɚ ʁɟ ɩɪɢɦɟɧɚ ɉɇ ɪɟɡɭɥɬɨɜɚɥɚ ɭ ɫɢɝɧɢɮɢɤɚɧɬɧɨ ɧɢɠɨʁ ɫɬɨɩɢ ɫɦɪɬɧɨɫɬɢ ɭ ɩɨɪɟђɟʃɭ ɫɚ ɩɚɰɢʁɟɧɬɢɦɚ ɥɟɱɟɧɢɦ Ɋɇ, ɩɪɢ ɱɟɦɭ ɧɢʁɟ ɛɢɥɨ ɫɢɝɧɢɮɢɤɚɧɬɧɨ ɡɧɚɱɚʁɧɟ ɪɚɡɥɢɤɟ ɭ ɫɬɨɩɢ ɪɟɤɭɪɟɧɰɢʁɟ ɬɭɦɨɪɚ ɢ ɩɨɫɬɨɩɟɪɚɬɢɜɧɢɦ ɤɨɦɩɥɢɤɚɰɢʁɚɦɚ. Ɂɚɤʂɭɱɚɤ ɫɬɭɞɢʁɟ ʁɟ ɞɚ ɉɇ ɩɪɟɞɫɬɚɜʂɚ ɦɟɬɨɞɭ ɢɡɛɨɪɚ ɡɚ ɥɟɱɟʃɟ ɥɨɤɚɥɢɡɨɜɚɧɨɝ ɤɚɪɰɢɧɨɦɚ ɛɭɛɪɟɝɚ ɭ Ɍ1 ɫɬɚɞɢʁɭɦɭ (<7cm)225. Ɇɚɞɚ ɪɟɡɭɥɬɚɬɢ ɨɜɢɯ ɫɬɭɞɢʁɚ ɫɭɝɟɪɢɲɭ ɩɪɢɦɟɧɭ ɉɇ ɡɚ ɥɨɤɚɥɢɡɨɜɚɧɟ ɬɭɦɨɪɫɤɟ ɩɪɨɦɟɧɟ ɤɚɞ ɝɨɞ ʁɟ ɬɨ ɦɨɝɭʄɟ, ɧɟɡɚɜɢɫɧɨ ɨɞ ɞɢɦɟɧɡɢʁɚ ɬɭɦɨɪɚ, ɨɧɚ ɫɟ ɢ ɞɚʂɟ ɧɟɞɨɜɨʂɧɨ ɩɪɢɦɟʃɭʁɟ. Ɍɚ ɱɢʃɟɧɢɰɟ ɭɤɚɡɭʁɟ ɞɚ ɨɞɥɭɤɚ ɯɢɪɭɪɝɚ ɞɚ ɩɪɢɦɟɧɢ ɉɇ ɜɢɲɟ ɡɚɜɢɫɢ ɨɞ ɥɨɤɚɥɢɡɚɰɢʁɟ ɬɭɦɨɪɚ, ɬɟɯɧɢɱɤɟ ɦɨɝɭʄɧɨɫɬɢ ɢ ɢɫɤɭɫɬɜɚ ɯɢɪɭɪɝɚ, ɚ ɪɟђɟ ɨɞ ɞɢɦɟɧɡɢʁɟ ɬɭɦɨɪɚ164. ɍ ɧɚɲɨʁ ɫɬɭɞɢʁɢ ɨɩɟɪɚɬɢɜɧɨ ʁɟ ɥɟɱɟɧ 41 ɩɚɰɢʁɟɧɬ, ɩɪɢ ɱɟɦɭ ʁɟ ɤɨɞ 33 (80,49%) ɩɚɰɢʁɟɧɚɬɚ ɩɪɢɦɟʃɟɧɚ ɨɬɜɨɪɟɧɚ ɬɪɚɧɫɥɭɦɛɚɥɧɚ Ɋɇ, ɚ ɤɨɞ 8 (19,51%) ɩɚɰɢʁɟɧɚɬɚ ɩɪɢɦɟʃɟɧɚ ʁɟ ɨɬɜɨɪɟɧɚ ɬɪɚɧɫɥɭɦɛɚɥɧɚ ɉɇ. Ʉɨɞ 29 (70,7%) ɩɚɰɢʁɟɧɚɬɚ ɬɭɦɨɪɢ ɫɭ ɛɢɥɢ ɞɢɦɟɧɡɢʁɚ ɦɚʃɢɯ ɨɞ 7cm, ɚ ɤɨɞ 12 (29,3%) ɩɚɰɢʁɟɧɚɬɚ ɬɭɦɨɪɢ ɫɭ ɛɢɥɢ ɞɢɦɟɧɡɢʁɚ ɜɟʄɢɯ ɨɞ 7cm. ɇɚɲɢ ɪɟɡɭɥɬɚɬɢ ɫɟ ɩɨɤɥɚɩɚʁɭ ɫɚ ɪɟɡɭɥɬɚɬɢɦɚ ɫɬɭɞɢʁɟ Dall’OglТo ɢ ɫɚɪ. ɤɨʁɢ ɫɭ ɢɦɚɥɢ ɫɥɢɱɧɭ ɞɢɫɬɪɢɛɭɰɢʁɭ ɬɭɦɨɪɚ ɩɪɟɦɚ ɞɢɦɟɧɡɢʁɚɦɚ (73,5% ɩɚɰɢʁɟɧɚɬɚ ɢɦɚɥɨ ʁɟ ɬɭɦɨɪɟ ɦɚʃɟ ɨɞ 7cm, ɚ 26,5% ɩɚɰɢʁɟɧɚɬɚ ʁɟ ɢɦɚɥɨ ɬɭɦɨɪɟ ɜɟʄɟ ɨɞ 7cm), ɩɪɢ ɱɟɦɭ ʁɟ ɩɪɢɦɟɧɨɦ Ɋɇ ɥɟɱɟɧɨ 79,3% ɩɚɰɢʁɟɧɚɬɚ, ɚ ɩɪɢɦɟɧɨɦ ɉɇ 20,7%226. ɍ ɧɚɲɨʁ ɝɪɭɩɢ ɨɛɨɥɟɥɢɯ ɡɧɚɱɚʁɧɨ ɜɟʄɢ ɛɪɨʁ ɛɨɥɟɫɧɢɤɚ ɥɟɱɟɧ ʁɟ ɪɚɞɢɤɚɥɧɨɦ ɧɟɮɪɟɤɬɨɦɢʁɨɦ. ɉɪɢ ɬɨɦɟ, ɤɨɞ ɩɚɰɢʁɟɧɚɬɚ ɫɚ ɬɭɦɨɪɢɦɚ ɦɚʃɢɦ ɨɞ 4 cm, 7 (38,9%) ɩɚɰɢʁɟɧɚɬɚ ɥɟɱɟɧɨ ʁɟ ɩɚɪɰɢʁɚɥɧɨɦ ɧɟɮɪɟɤɬɨɦɢʁɨɦ, ɞɨɤ ʁɟ ɤɨɞ ɨɫɬɚɥɢɯ 11 (61,1%) ɩɪɢɦɟʃɟɧɚ ɪɚɞɢɤɚɥɧɚ ɧɟɮɪɟɤɬɨɦɢʁɚ. ɋɜɢ ɩɚɰɢʁɟɧɬɢ ɤɨʁɢ ɫɭ ɥɟɱɟɧɢ ɉɇ ɢɦɚɥɢ ɫɭ Ɍ1ɚ ɩɚɬɨɥɨɲɤɢ ɫɬɚɞɢʁɭɦ ɛɨɥɟɫɬɢ, ɞɨɤ ʁɟ ɭ ɝɪɭɩɢ ɩɚɰɢʁɟɧɚɬɚ ɤɨʁɢ ɫɭ ɥɟɱɟɧɢ Ɋɇ, ɫɚɦɨ 3 ɩɚɰɢʁɟɧɬɚ ɢɦɚɥɨ Ɍ3ɚ ɩɚɬɨɥɨɲɤɢ ɫɬɚɞɢʁɭɦ ɛɨɥɟɫɬɢ, ɚ ɨɫɬɚɥɢɯ 8 ɩɚɰɢʁɟɧɚɬɚ Ɍ1ɚ ɩɚɬɨɥɨɲɤɢ ɫɬɚɞɢʁɭɦ. Ɋɚɡɥɨɝ ɩɪɢɦɟɧɟ ɪɚɞɢɤɚɥɧɟ ɧɟɮɪɟɤɬɨɦɢʁɟ ɤɨɞ ɪɟɥɚɬɢɜɧɨ ɜɟɥɢɤɨɝ ɛɪɨʁɚ ɩɚɰɢʁɟɧɚɬɚ ɫɚ Ɍ1ɚ ɫɬɚɞɢʁɭɦɨɦ ɛɨɥɟɫɬɢ ɭ ɧɚɲɨʁ ɝɪɭɩɢ ɨɛɨɥɟɥɢɯ ɛɢɥɚ ʁɟ ɢɧɬɪɚɨɩɟɪɚɬɢɜɧɚ ɩɪɨɰɟɧɚ ɭɪɨɥɨɝɚ ɞɚ ɡɛɨɝ ɩɨɥɨɠɚʁɚ ɬɭɦɨɪɫɤɟ ɩɪɨɦɟɧɟ ɧɢʁɟ ɦɨɝɭʄɟ ɭɱɢɧɢɬɢ ɩɚɪɰɢʁɚɥɧɭ ɧɟɮɪɟɤɬɨɦɢʁɭ. Ɂɚ ɪɚɡɥɢɤɭ ɨɞ ɧɚɲɢɯ ɪɟɡɭɥɬɚɬɚ,ɭ ɪɟɬɪɨɫɩɟɤɬɢɜɧɨʁ ɫɬɭɞɢʁɢThompson ɢ ɫɚɪ. ɫɩɪɨɜɟɞɟɧɨʁ ɧɚ 1533 ɩɚɰɢʁɟɧɬɚ ɥɟɱɟɧɚ ɭ ɩɟɪɢɨɞɭ 2000-2007. ɝɨɞɢɧɟ, 90% ɩɚɰɢʁɟɧɚɬɚ ɫɚ Ɍ1ɚ ɬɭɦɨɪɢɦɚ ɥɟɱɟɧɨ ʁɟ ɩɚɪɰɢʁɚɥɧɨɦ ɧɟɮɪɟɤɬɨɦɢʁɨɦ227.ɍ ɝɪɭɩɢ ɩɚɰɢʁɟɧɚɬɚ ɫɚ ɬɭɦɨɪɢɦɚ ɞɢɦɟɧɡɢʁɚ 4,1-7 cm, 9 ɩɚɰɢʁɟɧɚɬɚ ʁɟ ɢɦɚɥɨ Ɍ1ɛ ɩɚɬɨɥɨɲɤɢ ɫɬɚɞɢʁɭɦ ɛɨɥɟɫɬɢ, ɚ 2 ɩɚɰɢʁɟɧɬɚ Ɍ3ɚ ɩɚɬɨɥɨɲɤɢ ɫɬɚɞɢʁɭɦ. Ɉɞ ɭɤɭɩɧɨɝ ɛɪɨʁɚ, 1(9%) ɩɚɰɢʁɟɧɬ ʁɟ ɥɟɱɟɧ ɩɪɢɦɟɧɨɦ ɉɇ, ɞɨɤ ʁɟ ɨɫɬɚɥɢɯ 10 (91%) ɥɟɱɟɧɨ ɩɪɢɦɟɧɨɦ Ɋɇ. ɉɚɪɰɢʁɚɥɧɚ ɧɟɮɪɟɤɬɨɦɢʁɚ ɩɪɢɦɟʃɟɧɚ ʁɟ ɫɚɦɨ ɤɨɞ ɩɚɰɢʁɟɧɬɚ ɫɚ ɪɟɤɭɪɟɧɬɧɢɦ ɦɭɥɬɢɮɨɤɚɥɧɢɦ ɬɭɦɨɪɨɦ ɧɚ ɫɨɥɢɬɚɪɧɨɦ ɛɭɛɪɟɝɭ. ɇɚɲɢ ɪɟɡɭɥɬɚɬɢ ɫɭ ɫɥɢɱɧɢ ɪɟɡɭɥɬɚɬɢɦɚ ɫɬɭɞɢʁɟMilonas ɢ ɫɚɪ., ɭ ɤɨʁɨʁ ʁɟ ɨɞ 354 ɩɚɰɢʁɟɧɬɚ ɫɚ ɬɭɦɨɪɫɤɨɦ ɩɪɨɦɟɧɨɦ ɞɢɦɟɧɡɢʁɚ 4-7 cm, 90,3% ɥɟɱɟɧɨ ɩɪɢɦɟɧɨɦ Ɋɇ, ɚ 9,7% ɩɪɢɦɟɧɨɦ ɉɇ223.ɍ ɧɚɲɨʁ ɝɪɭɩɢ ɨɛɨɥɟɥɢɯ ɤɨɞ ɫɜɢɯ 12 (100%) ȾɂɋɄɍɋɂȳȺ 103 ɩɚɰɢʁɟɧɚɬɚ ɫɚ ɬɭɦɨɪɢɦɚ ɜɟʄɢɦ ɨɞ 7 cm ɩɪɢɦɟʃɟɧɚ ʁɟ ɪɚɞɢɤɚɥɧɚ ɧɟɮɪɟɤɬɨɦɢʁɚ. ɉɨɫɬɨɩɟɪɚɬɢɜɧɚ ɩɪɨɫɟɱɧɚ ɞɢɦɟɧɡɢʁɚ ɬɭɦɨɪɚ ɨɞɫɬɪɚʃɟɧɢɯ ɪɚɞɢɤɚɥɧɨɦ ɧɟɮɪɟɤɬɨɦɢʁɨɦ ɢɡɧɨɫɢɥɚ ʁɟ 5,44 ± 2,99 (2-13) cm. Fuhrman-ɨɜ ɫɢɫɬɟɦ ɨɞɪɟђɢɜɚʃɚ ɫɬɚɞɢʁɭɦɚ ɤɚɪɰɢɧɨɦɚ ɛɭɛɪɟɝɚ ɧɚ ɨɫɧɨɜɭ ɜɟɥɢɱɢɧɟ ɢ ɢɡɝɥɟɞɚ ʁɟɞɪɚ ɬɭɦɨɪɫɤɢɯ ʄɟɥɢʁɚ ɲɢɪɨɤɨ ʁɟ ɩɪɢɯɜɚʄɟɧ ɭ ɩɚɬɨɥɨɲɤɨʁ ɩɪɚɤɫɢ ɢ ɩɪɟɞɫɬɚɜʂɚ ɧɟɡɚɜɢɫɧɢ ɩɪɟɞɢɤɬɨɪ ɩɪɟɠɢɜʂɚɜɚʃɚ ɨɜɢɯ ɩɚɰɢʁɟɧɚɬɚ182. ɍ ɧɚɲɨʁ ɫɬɭɞɢʁɢ ʁɟ ɩɚɬɨɯɢɫɬɨɥɨɲɤɢ ɝɪɚɞɭɫ ɬɭɦɨɪɚ ɭ ɝɪɭɩɢ ɨɛɨɥɟɥɢɯ ɨɞɪɟђɟɧ ɩɪɢɦɟɧɨɦ ɤɥɚɫɢɱɧɨɝ Fuhrman- ɨɜɨɝ ɫɢɫɬɟɦɚ ɢ ɢɡɪɚɠɟɧ ɝɪɚɞɭɫɢɦɚ: G1, G2, G3 ɢ G4. ɇɚʁɜɟʄɢ ɩɪɨɰɟɧɚɬ ɩɚɰɢʁɟɧɚɬɚ ɭ ɧɚɲɨʁ ɫɬɭɞɢʁɢ ɢɦɚɨ ʁɟ G2 (78,05%) ɢ G3 (19,51%) ɝɪɚɞɭɫ ɬɭɦɨɪɚ, ɞɨɤ ʁɟ ɫɚɦɨ ʁɟɞɚɧ (2,44%) ɩɚɰɢʁɟɧɬ ɢɦɚɨ ɢɦɚɨ G4 ɝɪɚɞɭɫ. ɇɢʁɟɞɚɧ ɨɞ ɨɛɨɥɟɥɢɯ ɧɢʁɟ ɢɦɚɨ G1 ɝɪɚɞɭɫ ɬɭɦɨɪɚ. ɂ ɭ ɫɬɭɞɢʁɚɦɚ ɞɪɭɝɢɯ ɚɭɬɨɪɚ ɫɚ ɧɚʁɜɟʄɨɦ ɭɱɟɫɬɚɥɨɲʄɭ ʁɚɜʂɚʁɭ ɫɟ ɬɭɦɨɪɢ G2 ɢ G3 ɝɪɚɞɭɫɚ. Kuɢ ɫɚɪ. ɫɭ ɚɧɚɥɢɡɢɪɚɥɢ 657 ɛɨɥɟɫɧɢɤɚ ɫɚ ɫɄȻ, ɩɪɢ ɱɟɦɭ ʁɟ ɧɚʁɜɟʄɢ ɩɪɨɰɟɧɚɬ ɢɦɚɨ G2 (46,4%) ɢ G3 (37,6%) ɝɪɚɞɭɫ ɬɭɦɨɪɚ228. ɍ ɫɬɭɞɢʁɢ Zhangɢ ɫɚɪ. ɧɚʁɜɟʄɢ ɩɪɨɰɟɧɚɬ ɩɚɰɢʁɟɧɚɬɚ ɢɦɚɨ ʁɟ G3 ɝɪɚɞɭɫ ɬɭɦɨɪɚ (53,7%), ɞɨɤ ʁɟ ɫɚ G1 ɢɥɢ G2 ɝɪɚɞɭɫɨɦ ɛɢɥɨ 27,6% ɩɚɰɢʁɟɧɚɬɚ. ɍ ɨɜɨʁ ɫɬɭɞɢʁɢ, ɩɚɰɢʁɟɧɚɬɚ ɫɚ G4 ɫɬɚɞɢʁɭɦɨɦ ɬɭɦɨɪɚ ɛɢɥɨ ʁɟ 18,7%229. Ɂɧɚɱɚʁɧɨ ɦɚʃɢ ɩɪɨɰɟɧɚɬ (2,44%) ɩɚɰɢʁɟɧɚɬɚ ɫɚ G4 ɝɪɚɞɭɫɨɦ ɭ ɧɚɲɨʁ ɫɬɭɞɢʁɢ ɧɚʁɜɟɪɨɜɚɬɧɢʁɟ ʁɟ ɩɨɫɥɟɞɢɰɚ ɪɟɥɚɬɢɜɧɨ ɦɚɥɨɝ ɛɪɨʁɚ ɢɫɩɢɬɚɧɢɤɚ ɢ ɱɢʃɟɧɢɰɟ ɞɚ ʁɟ ɧɚʁɜɟʄɢ ɛɪɨʁ ɨɛɨɥɟɥɢɯ, ʃɢɯ 18 (43,9%), ɢɦɚɨ ɬɭɦɨɪɟ ɩɪɨɦɟɪɚ ɦɚʃɟɝ ɨɞ 4 cm. Ⱦɨ ɫɚɞɚ ɫɩɪɨɜɟɞɟɧɟ ɫɬɭɞɢʁɟ ɩɨɤɚɡɚɥɟ ɫɭ ɞɚ ɩɨɫɬɨʁɢ ɞɢɪɟɤɬɧɚ ɤɨɪɟɥɚɰɢʁɚ ɢɡɦɟђɭ ɜɟɥɢɱɢɧɟ ɬɭɦɨɪɚ ɢ ʃɟɝɨɜɨɝ ɦɚɥɢɝɧɨɝ ɩɨɬɟɧɰɢʁɚɥɚ. ɋɬɭɞɢʁɚ Zhang ɢ ɫɚɪ. ɫɩɪɨɜɟɞɟɧɚ ɧɚ 1867 ɩɚɰɢʁɟɧɚɬɚ ɥɟɱɟɧɢɯ ɯɢɪɭɪɲɤɢ ɡɛɨɝ ɬɭɦɨɪɚ ɛɭɛɪɟɝɚ, ɩɨɤɚɡɚɥɚ ʁɟ ɞɚ ɩɨɫɬɨʁɢ ɞɢɪɟɤɬɧɚ ɤɨɪɟɥɚɰɢʁɚ ɢɡɦɟђɭ ɜɟɥɢɱɢɧɟ ɬɭɦɨɪɚ ɢ ɧɭɤɥɟɚɪɧɨɝ ɝɪɚɞɭɫɚ, ɫɬɚɞɢʁɭɦɚ ɢ ɢɧɜɚɡɢɜɧɨɫɬɢ ɬɭɦɨɪɚ. Ɋɟɡɭɥɬɚɬɢ ɨɜɟ ɫɬɭɞɢʁɟ ɫɭ ɩɨɤɚɡɚɥɢ ɞɚ ɞɢʁɚɦɟɬɚɪ ɬɭɦɨɪɚ ɨɞ 4 cm ɩɪɟɞɫɬɚɜʂɚ ɝɪɚɧɢɱɧɭ ɞɢɦɟɧɡɢʁɭ ɬɭɦɨɪɚ ɧɚɤɨɧ ɱɟɝɚ ɞɨɥɚɡɢ ɞɨ ɡɧɚɱɚʁɧɟ ɩɪɨɦɟɧɟ ɭ ɚɝɪɟɫɢɜɧɨɫɬɢ ɬɭɦɨɪɚ, ɲɬɨ ɫɟ ɨɝɥɟɞɚ ɭ ɪɚɡɥɢɰɢ ɭ ɧɭɤɥɟɚɪɧɨɦ ɝɪɚɞɭɫɭ. Ɍɚɤɨђɟ, ɪɟɡɭɥɬɚɬɢ ɨɜɨɝ ɢɫɩɢɬɢɜɚʃɚ ɫɭ ɩɨɤɚɡɚɥɢ ɞɚ ɫɚ ɩɨɪɚɫɬɨɦ ɞɢɦɟɧɡɢʁɟ ɬɭɦɨɪɚ ɪɚɫɬɟ ɜɟɪɨɜɚɬɧɨʄɚ ɩɨɫɬɨʁɚʃɚ ɤɚɪɰɢɧɨɦɚ ɫɜɟɬɥɢɯ ʄɟɥɢʁɚ ɛɭɛɪɟɝɚ229. Thompson ɢ ɫɚɪ. ɫɩɪɨɜɟɥɢ ɫɭ ɪɟɬɪɨɫɩɟɤɬɢɜɧɭ ɫɬɭɞɢʁɭ ɧɚ 2.675 ɩɚɰɢʁɟɧɚɬɚ ɫɚ ɬɭɦɨɪɨɦ ɛɭɛɪɟɝɚ, ɨɞ ɱɟɝɚ ʁɟ ʃɢɯ 2.365 (88%) ɢɦɚɥɨ ɄȻ, ɞɨɤ ɫɭ ɨɫɬɚɥɨ ɛɢɥɢ ɛɟɧɢɝɧɢ ɬɭɦɨɪɢ. Ⱥɧɚɥɢɡɢɪɚɧɢ ɫɭ ɬɭɦɨɪɢ ɞɢʁɚɦɟɬɪɚ ɦɚʃɟɝ ɨɞ 1 cm, 1-7 cm ɢ ɜɟʄɢ ɨɞ 7 cm. Ɉɞ ɭɤɭɩɧɨɝ ɛɪɨʁɚ ɚɧɚɥɢɡɢɪɚɧɢɯ ɩɚɰɢʁɟɧɚɬɚ, 1.523 ɢɦɚɥɨ ʁɟ ɫɄȻ. ɉɨɤɚɡɚɧɨ ʁɟ ɞɚ ɫɚɦɨ 16% ɫɄȻ ɦɚʃɢɯ ɨɞ 3 cm ɫɭ ɢɦɚɥɢ ɜɢɫɨɤ ɧɭɤɥɟɚɪɧɢ ɝɪɚɞɭɫ (G3 ɢ G4), ɭ ɩɨɪɟђɟʃɭ ɫɚ 59% ɬɭɦɨɪɚ ɤɨʁɢ ɫɭ ɛɢɥɢ ɩɪɨɦɟɪɚ 7 cm ɢ ɜɟʄɢ. ɂ ɨɜɚ ɫɬɭɞɢʁɚ ʁɟ ɩɨɤɚɡɚɥɚ ɞɚ ɪɢɡɢɤ ɨɞ ɦɚɥɢɝɧɢɬɟɬɚ ɢ ɪɢɡɢɤ ɨɞ ɜɢɫɨɤɨɝ ɧɭɤɥɟɚɪɧɨɝ ɝɪɚɞɭɫɚ ɪɚɫɬɟ ɫɚ ɜɟɥɢɱɢɧɨɦ ɬɭɦɨɪɚ230. ɂɫɬɟ ɪɟɡɭɥɬɚɬɟ ɞɨɛɢɨ ʁɟ Frank ɢ ɫɚɪ. ɪɟɬɪɨɫɩɟɤɬɢɜɧɨɦ ɧɚɥɢɡɨɦ 2.770 ɩɚɰɢʁɟɧɚɬɚ. ɉɨɤɚɡɚɧɨ ʁɟ ɩɨɜɟʄɚʃɟ ɨɞ 32% ɬɭɦɨɪɚ ɜɢɫɨɤɨɝ ɧɭɤɥɟɚɪɧɨɝ ɝɪɚɞɭɫɚ ɡɚ ɫɜɚɤɢ 1 cm ɩɨɜɟʄɚʃɚ ɜɟɥɢɱɢɧɟ ɬɭɦɨɪɚ231. Suzuki ɢ ɫɚɪ. ɫɭ ɭ ɫɬɭɞɢʁɢ ɚɧɚɥɢɡɢɪɚɥɢ 338 ɩɚɰɢʁɟɧɚɬɚ ɤɨʁɢ ɫɭ ɢɦɚɥɢ T1a ɫɬɚɞɢʁɭɦ ɤɚɪɰɢɧɨɦɚ ɛɭɛɪɟɝɚ. Ɉɞ ɭɤɭɩɧɨɝ ɛɪɨʁɚ, ɧɚʁɜɟʄɢ ɩɪɨɰɟɧɚɬ ɱɢɧɢɥɢ ɫɭ ɩɚɰɢʁɟɧɬɢ ɫɚ G2 ɝɪɚɞɭɫɨɦ ɬɭɦɨɪɚ (71,6%), ɞɨɤ ʁɟɞ ɞɪɭɝɢ ɩɨ ɭɱɟɫɬɚɥɨɫɬɢ ɛɢɨ G1 (20,1%), ɩɨɬɨɦ G3 (6,2%) ɢ G4 (2,1%) ɝɪɚɞɭɫ. Ɂɧɚɱɚʁɧɨ ɧɢɠɢ ɩɪɨɰɟɧɚɬ ɬɭɦɨɪɚ ɫɚ G3 ɝɪɚɞɭɫɨɦ ɭ ɨɜɨʁ ɫɬɭɞɢʁɢ ɦɨɠɟ ɫɟ ɨɛʁɚɫɧɢɬɢ T1К ɫɬɚɞɢʁɭɦɨɦ ɛɨɥɟɫɬɢ232.ɂ ɭ ɧɚɲɨʁ ɫɬɭɞɢʁɢ ɩɨɫɬɨʁɚɥɚ ʁɟ ɞɢɪɟɤɬɧɚ ȾɂɋɄɍɋɂȳȺ 104 ɤɨɪɟɥɚɰɢʁɚ ɢɡɦɟђɭ ɜɟɥɢɱɢɧɟ ɬɭɦɨɪɚ ɢ ɧɭɤɥɟɚɪɧɨɝ ɝɪɚɞɭɫɚ. Ɍɚɤɨ ʁɟ ɭ ɝɪɭɩɢ ɬɭɦɨɪɚ ɞɢʁɚɦɟɬɪɚ ɞɨ 4 cm ɩɪɨɰɟɧɚɬ ɬɭɦɨɪɚ ɜɢɫɨɤɨɝ ɧɭɤɥɟɚɪɧɨɝ ɝɪɚɞɭɫɚ (G3 ɢ G4) ɢɡɧɨɫɢɨ 7,14%, ɭ ɝɪɭɩɢ ɞɢʁɚɦɟɬɪɚ 4 ɞɨ 7 cm ɢɡɧɨɫɢɨ ʁɟ 17,64%, ɞɨɤ ʁɟ ɭ ɝɪɭɩɢ ɬɭɦɨɪɚ ɞɢʁɚɦɟɬɪɚ ɩɪɟɤɨ 7 cm, ɩɪɨɰɟɧɚɬ ɨɧɢɯ ɫɚ ɜɢɫɨɤɢɦ ɧɭɤɥɟɚɪɧɢɦ ɝɪɚɞɭɫɨɦ ɢɡɧɨɫɢɨ 60%. Ʌɢɦɮɧɨ-ɜɚɫɤɭɥɚɪɧɚ ɢɧɜɚɡɢʁɚ (Ʌȼɂ) ɫɟ ɞɟɮɢɧɢɲɟ ɤɚɨ ɩɪɢɫɭɫɬɜɨ ɦɚɥɢɝɧɢɯ ʄɟɥɢʁɚ ɭ ɡɢɞɭ ɤɪɜɧɨɝ ɫɭɞɚ ɢɥɢ ɧɟɨɩɥɚɫɬɢɱɤɢɯ ɟɦɛɨɥɭɫɚ ɭ ɥɭɦɟɧɭ ɢɧɬɪɚɬɭɦɨɪɫɤɨɝ ɤɪɜɧɨɝ ɫɭɞɚ. ɍ ɫɬɭɞɢʁɚɦɚ ɤɨʁɟ ɫɭ ɢɫɩɢɬɢɜɚɥɟ ɩɪɨɝɧɨɫɬɢɱɤɢ ɡɧɚɱɚʁ Ʌȼɂ, ɞɨɤɚɡɚɧɚ ʁɟ ʃɟɧɚ ɩɨɜɟɡɚɧɨɫɬ ɫɚ ɜɢɲɢɦ ɫɬɚɞɢʁɭɦɨɦ ɢ ɝɪɚɞɭɫɨɦ ɬɭɦɨɪɚ, ɤɚɨ ɢ ɜɟʄɢɦ ɪɢɡɢɤɨɦ ɨɞ ɦɟɬɚɫɬɚɡɚ ɭ ɥɢɦɮɧɟ ɱɜɨɪɨɜɟ, ɤɚɨ ɢ ɭɞɚʂɟɧɢɯ ɦɟɬɚɫɬɚɡɚ233. Eisenberg ɢ ɫɚɪ. ɫɭ ɭ ɫɜɨʁɨʁ ɫɬɭɞɢʁɢ ɩɨɤɚɡɚɥɢ ɞɚ ʁɟ Ʌȼɂ ɛɢɥɚ ɩɨɜɟɡɚɧɚ ɫɚ ɩɨɜɟʄɚɧɢɦ ɪɢɡɢɤɨɦ ɨɞ ɪɚɡɜɨʁɚ ɦɟɬɚɫɬɚɡɚ ɢ ɫɦɪɬɧɢɦ ɢɫɯɨɞɨɦ ɤɨɞ ɨɛɨɥɟɥɢɯ ɨɞ ɤɚɪɰɢɧɨɦɚ ɫɜɟɬɥɢɯ ʄɟɥɢʁɚ ɛɭɛɪɟɝɚ234. Ʌɢɦɮɧɨ-ɜɚɫɤɭɥɚɪɧɚ ɢɧɜɚɡɢʁɚ ɩɪɟɞɫɬɚɜʂɚ ɡɧɚɱɚʁɚɧ ɩɪɨɝɧɨɫɬɢɱɤɢ ɮɚɤɬɨɪ ɧɚɤɨɧ ɪɚɞɢɤɚɥɧɟ ɧɟɮɪɟɤɬɨɦɢʁɟ ɤɨɞ ɤɥɢɧɢɱɤɢ ɧɟɦɟɬɚɫɬɚɬɫɤɢɯ ɤɚɪɰɢɧɨɦɚ ɛɭɛɪɟɝɚ. ɍɬɜɪђɟɧɨ ʁɟ ɞɚ ɫɟ ɫɬɨɩɚ ɩɪɨɝɪɟɫɢʁɟ ɤɪɟʄɟ ɨɞ 29% ɞɨ 39,2% ɤɨɞ ɬɭɦɨɪɚ ɫɚ Ʌȼɂ, ɧɚɫɭɩɪɨɬ 6,2% ɞɨ 17% ɤɨɞ ɨɧɢɯ ɛɟɡ Ʌȼɂ235. ɍ ɧɚɲɨʁ ɝɪɭɩɢ ɨɛɨɥɟɥɢɯ ɧɚʁɜɟʄɢ ɩɪɨɰɟɧɚɬ ɩɚɰɢʁɟɧɚɬɚ, 51,22% ɢɦɚɨ ʁɟ ɡɧɚɤɟ Ʌȼɂ, 31,71% ɩɚɰɢʁɟɧɚɬɚ ɢɦɚɨ ʁɟ ɡɧɚɤɟ ɥɢɦɮɧɟ ɢɥɢ ɜɚɫɤɭɥɚɪɧɟ ɢɧɜɚɡɢʁɟ, ɞɨɤ ɧɚʁɦɚʃɢ ɩɪɨɰɟɧɚɬ, 17,07% ɧɢʁɟ ɢɦɚɨ ɡɧɚɤɟ ɧɢ ɥɢɦɮɧɟ, ɧɢ ɜɚɫɤɭɥɚɪɧɟ ɬɭɦɨɪɫɤɟ ɢɧɜɚɡɢʁɟ. ɉɪɨɰɟɧɚɬ Ʌȼɂ ɭ ɧɚɲɨʁ ɝɪɭɩɢ ɨɛɨɥɟɥɢɯ ɛɢɨ ʁɟ ɧɟɲɬɨ ɜɢɲɢ ɭ ɩɨɪɟђɟʃɭ ɫɚ ɪɟɡɭɥɬɚɬɢɦɚ ɞɪɭɝɢɯ ɫɬɭɞɢʁɚ. ɍ ɫɬɭɞɢʁɢ Sevinc ɢ ɫɚɪ. Ʌȼɂ ʁɟ ɛɢɥɚ ɩɪɢɫɭɬɧɚ ɤɨɞ 17% ɩɚɰɢʁɟɧɚɬɚ ɢ ɤɨɪɟɥɢɪɚ ʁɟ ɫɚ ɝɪɚɞɭɫɨɦ ɢ ɜɟɥɢɱɢɧɨɦ ɬɭɦɨɪɚ235. ɍ ɫɬɭɞɢʁɢ ɲɩɚɧɫɤɢɯ ɚɭɬɨɪɚ ɫɩɪɨɜɟɞɟɧɨʁ ɧɚ 238 ɩɚɰɢʁɟɧɚɬɚ, ɤɨɞ 79 (33,2%) ɛɢɥɚ ʁɟ ɩɪɢɫɭɬɧɚ Ʌȼɂ233. ɍ ɫɬɭɞɢʁɢ Dall’OglТo ɢ ɫɚɪ. Ʌȼɂ ʁɟ ɛɢɥɚ ɩɪɢɫɭɬɧɚ ɤɨɞ 25,7% ɩɚɰɢʁɟɧɚɬɚ. Ɋɟɡɭɥɬɚɬɢ ɫɬɭɞɢʁɟ ɫɭ ɩɨɤɚɡɚɥɢ ɞɚ ɩɪɢɫɭɫɬɜɨ Ʌȼɂ, ɡɚʁɟɞɧɨ ɫɚ ɜɟɥɢɱɢɧɨɦ ɬɭɦɨɪɚ ɢ Furhman-ɨɜɢɦ ɝɪɚɞɭɫɨɦ, ɩɪɟɞɫɬɚɜʂɚ ɧɟɡɚɜɢɫɚɧ ɩɪɟɞɢɤɬɨɪ ɩɪɟɠɢɜʂɚɜɚʃɚ ɤɨɞ ɨɛɨɥɟɥɢɯ ɨɞ ɤɚɪɰɢɧɨɦɚ ɛɭɛɪɟɝɚ226. ɍɩɪɤɨɫ ɪɚɡɥɢɱɢɬɢɦ ɢɦɭɧɨɯɢɫɬɨɯɟɦɢʁɫɤɢɦ ɢ ɦɨɥɟɤɭɥɚɪɧɢɦ ɩɪɨɝɧɨɫɬɢɱɤɢɦ ɛɢɨɦɚɪɤɟɪɢɦɚ, ɤɥɚɫɢɱɧɢɩɨɫɬɨɩɟɪɚɬɢɜɧɢ ɌNМ (ɟɧɝɥ. ɫɤɪ. ɌNМ-tumour–node–metastasis) ɫɢɫɬɟɦ ɡɚ ɭɬɜɪђɢɜɚʃɟ ɫɬɚɞɢʁɭɦɚ ɬɭɦɨɪɚ ɛɭɛɪɟɝɚ ɧɚ ɨɫɧɨɜɭ ɜɟɥɢɱɢɧɟ ɬɭɦɨɪɚ, ɛɪɨʁɚ ɩɨɡɢɬɢɜɧɢɯ ɥɢɦɮɧɢɯ ɱɜɨɪɨɜɚ ɢ ɩɪɢɫɭɫɬɜɚ ɭɞɚʂɟɧɢɯ ɦɟɬɚɫɬɚɡɚ, ʁɨɲ ɭɜɟɤ ɩɪɟɞɫɬɚɜʂɚ ɡɥɚɬɧɢ ɩɪɨɝɧɨɫɬɢɱɤɢ ɫɬɚɧɞɚɪɞ. Ɉɞ ʁɚɧɭɚɪɚ 2010. ɭ ɭɩɨɬɪɟɛɢ ʁɟ ɫɟɞɦɚ ɌNМ ɤɥɚɫɢɮɢɤɚɰɢʁɚ ɤɚɪɰɢɧɨɦɚ ɛɭɛɪɟɝɚ180. ɍ ɧɚɲɨʁ ɝɪɭɩɢ ɨɛɨɥɟɥɢɯ ɧɚʁɜɟʄɢ ɛɪɨʁ ɩɚɰɢʁɟɧɚɬɚɢɦɚɨ ʁɟ ɌNМI ɫɬɚɞɢʁɭɦ ɛɨɥɟɫɬɢ, 23 (56,10%), ɢ ɌNМ III, ʃɢɯ 13 (31,71%). ɇɚʁɦɚʃɢ ɛɪɨʁ ɩɚɰɢʁɟɧɚɬɚ ɢɦɚɨ ʁɟ ɌNМ II ɫɬɚɞɢʁɭɦ, 3 (7,32%) ɩɚɰɢʁɟɧɬɚ, ɤɚɨ ɢ ɌNМIVɫɬɚɞɢʁɭɦ ɛɨɥɟɫɬɢ, 2 (4,88%) ɩɚɰɢʁɟɧɬɚ. Ɉɞ ɭɤɭɩɧɨɝ ɛɪɨʁɚ ɨɛɨɥɟɥɢɯ ɫɚɦɨ 2 (4,88%) ɩɚɰɢʁɟɧɬɚ ɢɦɚɥɚ ɫɭ ɦɟɬɚɫɬɚɬɫɤɭ ɛɨɥɟɫɬ, ɞɨɤ ʁɟ ɨɫɬɚɥɢɯ 39 (95,12%) ɩɚɰɢʁɟɧɚɬɚ ɢɦɚɥɨ ɥɨɤɚɥɢɡɨɜɚɧ ɨɛɥɢɤ ɛɨɥɟɫɬɢ. ɋɥɢɱɧɚ ɞɢɫɬɪɢɛɭɰɢʁɚ ɩɨɫɬɨɩɟɪɚɬɢɜɧɢɯ ɌNМ ɫɬɚɞɢʁɭɦɚ ɛɢɥɚ ʁɟ ɡɚɫɬɭɩʂɟɧɚ ɢ ɭ ɫɬɭɞɢʁɚɦɚ ɞɪɭɝɢɯ ɚɭɬɨɪɚ228, 229. ȾɂɋɄɍɋɂȳȺ 105 5.3. Ʉɨɧɰɟɧɬɪɚɰɢʁɚ KIM-1 ɭ ɭɪɢɧɭ ɨɛɨɥɟɥɢɯ ɨɞ ɤɚɪɰɢɧɨɦɚ ɫɜɟɬɥɢɯ ʄɟɥɢʁɚ ɛɭɛɪɟɝɚ Ʉɚɪɰɢɧɨɦ ɫɜɟɬɥɢɯ ʄɟɥɢʁɚ ɛɭɛɪɟɝɚ ɭɞɪɭɠɟɧ ʁɟ ɫɚ ɩɪɨɤɫɢɦɚɥɧɨɦ ɬɭɛɭɥɫɤɨɦ ʄɟɥɢʁɫɤɨɦ ɞɟɞɢɮɟɪɟɧɰɢʁɚɰɢʁɨɦ ɢ ɜɢɫɨɤɨɦ ɟɤɫɩɪɟɫɢʁɨɦ KIM-1. ɉɨɞ ɞɟʁɫɬɜɨɦ ɟɧɡɢɦɚ ɦɟɬɚɥɨɩɪɨɬɟɢɧɚɡɟ ɞɨɥɚɡɢ ɞɨ ɰɟɩɚʃɚ ʃɟɝɨɜɨɝ ɟɤɬɨɞɨɦɟɧɚ ɢ ɫɟɤɪɟɰɢʁɟ ɭ ɭɪɢɧ, ɝɞɟ ɫɟ ɦɨɠɟ ɞɟɬɟɤɬɨɜɚɬɢ ɤɚɨ 90 kDa ɬɟɠɚɤ ɫɨɥɭɛɢɥɧɢ ɩɪɨɬɟɢɧ, ɨɡɧɚɱɟɧ ɤɚɨ ɭɪɢɧɚɪɧɢ KIM-1 (uKIM- 1)123. ȼɟʄɢ ɛɪɨʁ ɩɪɨɫɩɟɤɬɢɜɧɢɯ ɫɬɭɞɢʁɚ ʁɟ ɩɨɤɚɡɚɨ ɫɢɝɧɢɮɢɤɚɧɬɧɨ ɜɢɲɭ ɩɪɟɨɩɟɪɚɬɢɜɧɭ ɤɨɧɰɟɧɬɪɚɰɢʁɭ ɨɜɨɝ ɛɢɨɦɚɪɤɟɪɚ ɭ ɭɪɢɧɭ ɩɚɰɢʁɟɧɚɬɚ ɨɛɨɥɟɥɢɯ ɨɞ ɫɄȻ, ɤɚɨ ɢ ɩɨɜɟɡɚɧɨɫɬ ʃɟɝɨɜɟ ɤɨɧɰɟɧɬɪɚɰɢʁɟ ɫɚ ɩɚɬɨɯɢɫɬɨɥɨɲɤɢɦ ɤɚɪɚɤɬɟɪɢɫɬɢɤɚɦɚ ɬɭɦɨɪɚ145, 146, 147, 148. ɍ ɧɚɲɨʁ ɫɬɭɞɢʁɢ ɫɭ ɩɪɟɨɩɟɪɚɬɢɜɧɟ ɜɪɟɞɧɨɫɬɢ uKIM-1 ɛɢɥɟ ɫɬɚɬɢɫɬɢɱɤɢ ɡɧɚɱɚʁɧɨ ɜɢɲɟ ɭ ɨɞɧɨɫɭ ɧɚ ɩɨɫɬɨɩɟɪɚɬɢɜɧɟ ɜɪɟɞɧɨɫɬɢ (p=0.044). ɉɨɫɬɨɩɟɪɚɬɢɜɧɨ ɞɨɥɚɡɢ ɞɨ ɫɧɢɠɟʃɚ ɜɪɟɞɧɨɫɬɢ uKIM-1 ɢ ɧɚ ɩɪɜɨʁ ɢ ɧɚ ɞɪɭɝɨʁ ɩɨɫɬɨɩɟɪɚɬɢɜɧɨʁ ɤɨɧɬɪɨɥɢ, ɩɪɢ ɱɟɦɭ ʁɟ ɞɨɛɢʁɟɧɚ ɫɬɚɬɢɫɬɢɱɤɢ ɡɧɚɱɚʁɧɨ ɧɢɠɚ ɜɪɟɞɧɨɫɬ ɢ ɡɚ ɚɩɫɨɥɭɬɧɭ (p*=0.006) ɢ ɡɚ ɤɨɪɢɝɨɜɚɧɭ (p*= 0.0003) ɤɨɧɰɟɧɬɪɚɰɢʁɭ uKIM-1 ɬɟɤ ɧɚ ɞɪɭɝɨʁ ɩɨɫɬɨɩɟɪɚɬɢɜɧɨʁ ɤɨɧɬɪɨɥɢ. Ɋɚɡɥɨɝ ɡɛɨɝ ɱɟɝɚ ɧɚ ɩɪɜɨʁ ɤɨɧɬɪɨɥɢ ɧɢʁɟ ɞɨɲɥɨ ɞɨ ɫɬɚɬɢɫɬɢɱɤɢ ɡɧɚɱɚʁɧɨɝ ɫɧɢɠɟʃɚ uKIM-1 ʁɟ ɧɚʁɜɟɪɨɜɚɬɧɢʁɟ ɩɪɨɞɭɤɰɢʁɚ KIM-1 ɧɟɡɚɜɢɫɧɚ ɨɞ ɬɭɦɨɪɚ, ɚ ɧɚɫɬɚɥɚ ɭ ɫɤɥɨɩɭ ɢɫɯɟɦɢʁɫɤɟ ɥɟɡɢʁɟ ɢɡɚɡɜɚɧɟ ɩɪɢɜɪɟɦɟɧɢɦ ɡɚɬɜɚɪɚʃɟɦ ɪɟɧɚɥɧɟ ɚɪɬɟɪɢʁɟ ɬɨɤɨɦ ɩɚɪɰɢʁɚɥɧɟ ɧɟɮɪɟɤɬɨɦɢʁɟ. ɇɚɢɦɟ, ɩɨɤɚɡɚɥɢ ɫɦɨ ɞɚ ʁɟ ɭ ɝɪɭɩɢ ɩɚɰɢʁɟɧɚɬɚ, ɭɤɭɩɧɨ 8, ɤɨʁɢ ɫɭ ɛɢɥɢ ɩɨɞɜɪɝɧɭɬɢ ɩɚɪɰɢʁɚɥɧɨʁ ɧɟɮɪɟɤɬɨɦɢʁɢ, ɤɨɧɰɟɧɬɪɚɰɢʁɚ uKIM-1 ɧɚ ɩɪɜɨʁ ɩɨɫɬɨɩɟɪɚɬɢɜɧɨʁ ɤɨɧɬɪɨɥɢ ɛɢɥɚ ɞɜɨɫɬɪɭɤɨ ɜɢɲɚ ɭ ɨɞɧɨɫɭ ɧɚ ɩɪɟɨɩɟɪɚɬɢɜɧɟ ɜɪɟɞɧɨɫɬɢ. ɉɨɪɟђɟʃɟɦ ɩɪɟɨɩɟɪɚɬɢɜɧɟ ɜɪɟɞɧɨɫɬɢ ɚɩɫɨɥɭɬɧɟ ɢ ɤɨɪɢɝɨɜɚɧɟ ɤɨɧɰɟɧɬɪɚɰɢʁɟ uKIM-1 ɢɡɦɟђɭ ɝɪɭɩɟ ɨɛɨɥɟɥɢɯ ɢ ɤɨɧɬɪɨɥɧɟ ɝɪɭɩɟ ɡɞɪɚɜɢɯ, ɞɨɛɢʁɟɧɚ ʁɟ ɫɬɚɬɢɫɬɢɱɤɢ ɡɧɚɱɚʁɧɨ ɜɢɲɚ ɜɪɟɞɧɨɫɬ uKIM-1 ɭ ɝɪɭɩɢ ɨɛɨɥɟɥɢɯ (p=0.0015). ɉɪɢ ɬɨɦɟ, ɞɨɛɢʁɟɧ ʁɟ ɨɞɪɟђɟɧɢ ɫɬɟɩɟɧ ɩɪɟɤɥɚɩɚʃɚ ɭ ɨɩɫɟɝɭ ɤɨɧɰɟɧɬɪɚɰɢʁɚ uKIM-1 ɢɡɦɟђɭ ɝɪɭɩɟ ɨɛɨɥɟɥɢɯ (0.076-9.8 ng/mgUcr) ɢɝɪɭɩɟ ɡɞɪɚɜɢɯ (0.043-0.604 ng/mgUcr), ɲɬɨ ɧɚɜɨɞɟ ɢ Morrissey ɢ ɫɚɪ. ɭ ɫɜɨʁɨʁ ɫɬɭɞɢʁɢ146. ɇɚ ɩɪɜɨʁ ɩɨɫɬɨɩɟɪɚɬɢɜɧɨʁ ɤɨɧɬɪɨɥɢ ɢ ɞɚʂɟ ɫɭ ɤɨɪɢɝɨɜɚɧɟ ɜɪɟɞɧɨɫɬɢ uKIM-1 ɜɢɲɟ ɭ ɝɪɭɩɢ ɨɛɨɥɟɥɢɯ ɚɥɢ ɬɚ ɪɚɡɥɢɤɚ ɧɢʁɟ ɫɬɚɬɢɫɬɢɱɤɢ ɡɧɚɱɚʁɧɚ (p=0.056). ɉɨɪɟђɟʃɟɦ ɚɩɫɨɥɭɬɧɢɯ ɜɪɟɞɧɨɫɬɢ ɞɨɛɢʁɟɧɚ ʁɟ ɢɫɬɚ ɞɢɧɚɦɢɤɚ ɫɦɚʃɟʃɚ, ɫ ɬɢɦ ɞɚ ɫɟ ɧɚ ɩɪɜɨʁ ɤɨɧɬɪɨɥɢ ʁɨɲ ɭɜɟɤ ɨɞɪɠɚɜɚ ɫɬɚɬɢɫɬɢɱɤɢ ɡɧɚɱɚʁɧɨ ɜɢɲɚ ɤɨɧɰɟɧɬɪɚɰɢʁɚ uKIM-1 ɭ ɝɪɭɩɢ ɨɛɨɥɟɥɢɯ (p= 0.045), ɞɚ ɛɢ ɧɚ ɞɪɭɝɨʁ ɤɨɧɬɪɨɥɢ ɫɪɟɞʃɟ ɜɪɟɞɧɨɫɬɢ uKIM-1 ɛɢɥɟ ɫɤɨɪɨ ɢɧɞɟɧɬɢɱɧɟ ɭ ɨɛɟ ɝɪɭɩɟ. ɇɚɲɢ ɪɟɡɭɥɬɚɬɢ ɫɟ ɩɨɤɥɚɩɚʁɭ ɫɚ ɪɟɡɭɥɬɚɬɢɦɚ ɫɬɭɞɢʁɚ ɞɪɭɝɢɯ ɚɭɬɨɪɚ. ɋɬɭɞɢʁɚ Han ɢ ɫɚɪ. ʁɟ ɛɢɥɚ ɩɪɜɚ ɫɬɭɞɢʁɚ ɤɨʁɚ ʁɟ ɧɚ ɦɚɥɨɦ ɛɪɨʁɭ ɩɚɰɢʁɟɧɚɬɚ (ɭɤɭɩɧɨ 5), ɤɨʁɢ ɫɭ ɢɦɚɥɢ ɩɪɟ ɢ ɩɨɫɬɨɩɟɪɚɬɢɜɧɟ ɜɪɟɞɧɨɫɬɢ uKIM-1, ɩɨɤɚɡɚɥɚ ɞɚ ɩɨɫɬɨɩɟɪɚɬɢɜɧɨ ɞɨɥɚɡɢ ɞɨ ɡɧɚɱɚʁɧɨɝ ɫɦɚʃɟʃɚ ʃɟɝɨɜɟ ɤɨɧɰɟɧɬɪɚɰɢʁɟ ɭ ɭɪɢɧɭ145. Morrissey ɢ ɫɚɪ. ɫɭ ɭ ɫɜɨʁɨʁ ɫɬɭɞɢʁɢ ɩɨɤɚɡɚɥɢ ɞɚ ɫɭ ɩɪɟɨɩɟɪɚɬɢɜɧɟ ɜɪɟɞɧɨɫɬɢ uKIM-1 ɤɨɞ ɩɚɰɢʁɟɧɚɬɚ ɫɚ ɫɄȻ ɫɬɚɬɢɫɬɢɱɤɢ ɡɧɚɱɚʁɧɨ ɜɢɲɟ ɭ ɨɞɧɨɫɭ ɧɚ ʃɟɝɨɜɭ ɜɪɟɞɧɨɫɬ ɭ ɤɨɧɬɪɨɥɧɨʁ ɝɪɭɩɢ ɡɞɪɚɜɢɯ. Ʉɚɨ ɢ ɭ ɧɚɲɨʁ ɫɬɭɞɢʁɢ ɩɨɫɬɨʁɚɨ ʁɟ ɦɚʃɢ ɫɬɟɩɟɧ ɩɪɟɤɥɚɩɚʃɚ ɭ ɨɩɫɟɝɭ ɜɪɟɞɧɨɫɬɢ uKIM-1 ɢɡɦɟђɭ ɝɪɭɩɚ. ɉɨɫɬɨɩɟɪɚɬɢɜɧɨ, ɬɚɤɨђɟ ɞɨɥɚɡɢ ɞɨ ɫɬɚɬɢɫɬɢɱɤɢ ɡɧɚɱɚʁɧɨɝ ɫɦɚʃɟʃɚ ɤɨɧɰɟɧɬɪɚɰɢʁɟ uKIM-1. ɉɪɢ ɬɨɦ ɫɦɚʃɟʃɟ ʁɟ ɛɢɥɨ ɧɟɩɨɬɩɭɧɨ ɢ ɤɨɧɰɟɧɬɪɚɰɢʁɚ uKIM-1 ɧɚ ɤɨɧɬɪɨɥɧɨɦ ɩɪɟɝɥɟɞɭ 1-3 ɦɟɫɟɰɚ ȾɂɋɄɍɋɂȳȺ 106 ɧɚɤɨɧ ɨɩɟɪɚɰɢʁɟ ɨɫɬɚɥɚ ʁɟ ɫɭɲɬɢɧɫɤɢ ɜɟʄɚ ɭ ɝɪɭɩɢ ɨɛɨɥɟɥɢɯ ɨɞ ɫɄȻ146. ɍ ɫɬɭɞɢʁɢ Han ɢ ɫɚɪ. ɚɭɬɨɪɢ ɧɚɝɥɚɲɚɜɚʁɭ ɞɚ ɩɨɫɬɨɩɟɪɚɬɢɜɧɨ ɧɢʁɟ ɞɨɲɥɨ ɞɨ ɫɦɚʃɟʃɚ uKIM-1 ɧɚ ɧɟɞɟɬɟɤɬɚɛɢɥɧɟ ɜɪɟɞɧɨɫɬɢ, ɚ ɤɚɨ ɦɨɝɭʄɢ ɪɚɡɥɨɝ ɡɚ ɬɨ ɧɚɜɨɞɟ ɦɨɝɭʄɧɨɫɬ ɩɨɫɬɨʁɚʃɚ ɬɭɦɨɪɚ ɭ ɤɨɧɬɪɚɥɚɬɟɪɚɥɧɨɦ ɛɭɛɪɟɝɭ ɢɥɢ ɧɟɞɢʁɚɝɧɨɫɬɢɤɨɜɚɧɨ ɬɭɛɭɥɨɢɧɬɟɪɫɬɢɰɢɫɤɨ ɛɭɛɪɟɠɧɨ ɨɲɬɟʄɟʃɟ145. ɍ ɧɚɲɨʁ ɫɬɭɞɢʁɢ ɜɪɟɞɧɨɫɬ uKIM-1 ɧɚ ɞɪɭɝɨʁ ɤɨɧɬɪɨɥɢ, ɦɟɫɟɰ ɞɚɧɚ ɧɚɤɨɧ ɨɩɟɪɚɰɢʁɟ, ɛɢɥɚ ʁɟ ɫɤɨɪɨ ɢɧɞɟɧɬɢɱɧɚ ɤɚɨ ɭ ɝɪɭɩɢ ɡɞɪɚɜɢɯ. Ɋɟɡɭɥɬɚɬɢ ɩɪɨɫɩɟɤɬɢɜɧɟ ɫɬɭɞɢʁɟ Zhang ɢ ɫɚɪ. ɫɭ ɩɨɤɚɡɚɥɢ ɞɚ ɩɨɫɬɨɩɟɪɚɬɢɜɧɨ ɞɨɥɚɡɢ ɞɨ ɡɧɚɱɚʁɧɨɝ ɫɦɚʃɟʃɚ ɤɨɧɰɟɧɬɪɚɰɢʁɟ uKIM-1 ɭ ɝɪɭɩɢ ɬɭɦɨɪɚ ɤɨʁɢ ɫɭ ɩɨɤɚɡɢɜɚɥɢ KIM-1 ɬɤɢɜɧɭ ɩɨɡɢɬɢɜɧɨɫɬ148.Ɂɚ ɪɚɡɥɢɤɭ ɨɞ ɧɚɲɢɯ, ɤɚɨ ɢ ɪɟɡɭɥɬɚɬɚ ɞɪɭɝɢɯ ɚɭɬɨɪɚ,ʁɟɞɢɧɨ ɫɭ ɭ ɫɬɭɞɢʁɢ Shalabi ɢ ɫɚɪ. ɪɚɡɥɢɤɟ ɭ ɤɨɧɰɟɧɬɪɚɰɢʁɢ uKIM-1 ɭ ɝɪɭɩɢ ɨɛɨɥɟɥɢɯ ɨɞ ɫɄȻ ɛɢɥɟ ɞɢɫɤɪɟɬɧɨ ɜɢɲɟ ɭ ɨɞɧɨɫɭ ɧɚ ɤɨɧɬɪɨɥɧɭ ɝɪɭɩɭ ɬʁ. ɪɚɡɥɢɤɚ ɧɢʁɟ ɛɢɥɚ ɫɬɚɬɢɫɬɢɱɤɢ ɡɧɚɱɚʁɧɚ147. Ɉɞ ɢɧɬɟɪɟɫɚ ɡɚ ɧɚɲɟ ɢɫɬɪɚɠɢɜɚʃɟ ʁɟ ɛɢɥɨ ɞɚ ɭɬɜɪɞɢɦɨ ɩɪɢ ɤɨʁɨʁ ɞɢɦɟɧɡɢʁɢ ɬɭɦɨɪɚ ɛɭɛɪɟɝɚ ɞɨɥɚɡɢ ɞɨ ɥɭɱɟʃɚ uKIM-1 ɭ ɤɨɧɰɟɧɬɪɚɰɢʁɢ ɤɨʁɚ ʁɟ ɫɬɚɬɢɫɬɢɱɤɢ ɡɧɚɱɚʁɧɨ ɜɢɲɚ ɭ ɨɞɧɨɫɭ ɧɚ ʃɟɝɨɜɭ ɤɨɧɰɟɧɬɪɚɰɢʁɭ ɭ ɝɪɭɩɢ ɡɞɪɚɜɢɯ. Ʉɚɞɚ ɫɦɨ ɭɩɨɪɟɞɢɥɢ ɜɪɟɞɧɨɫɬɢ ɚɩɫɨɥɭɬɧɟ ɤɨɧɰɟɧɬɪɚɰɢʁɟ uKIM-1 ɩɪɟɦɚ ɤɚɬɟɝɨɪɢʁɢ ɜɟɥɢɱɢɧɟ ɬɭɦɨɪɚ(≤4 cm, 4.1-7 cm ɢ >7cm) ɭ ɝɪɭɩɢ ɨɛɨɥɟɥɢɯ ɢ ɭɪɢɧɚɪɧɟ ɤɨɧɰɟɧɬɪɚɰɢʁɟ KIM-1 ɭ ɝɪɭɩɢ ɡɞɪɚɜɢɯ, ɞɨɛɢʁɟɧɚ ʁɟ ɫɬɚɬɢɫɬɢɱɤɢ ɡɧɚɱɚʁɧɨ ɜɟʄɚ ɜɪɟɞɧɨɫɬ uKIM-1 ɭ ɝɪɭɩɢ ɨɛɨɥɟɥɢɯ ɭ ɨɞɧɨɫɭ ɧɚ ɝɪɭɩɭ ɡɞɪɚɜɢɯ (p=2.53*10-6).ɉɨɪɟђɟʃɟɦ ɚɩɫɨɥɭɬɧɟ ɤɨɧɰɟɧɬɪɚɰɢʁɟ uKIM-1 ɩɪɟɦɚ ɤɚɬɟɝɨɪɢʁɢ ɜɟɥɢɱɢɧɟ ɬɭɦɨɪɚ, ɩɨɤɚɡɚɥɢ ɫɦɨ ɞɚ ʃɟɝɨɜɚ ɤɨɧɰɟɧɬɪɚɰɢʁɚ ɫɪɚɡɦɟɪɧɚ ɜɟɥɢɱɢɧɢ ɬɭɦɨɪɚ. Ɉɞ ɩɨɫɟɛɧɨɝ ɡɧɚɱɚʁɚ ʁɟ ɞɚ ɫɦɨ ɭ ɧɚɲɟɦ ɢɫɬɪɚɠɢɜɚʃɭ ɩɨɤɚɡɚɥɢ ɞɚ ʁɟ ɭ ɭɪɢɧɭ ɩɚɰɢʁɟɧɚɬɚ ɫɚ ɬɭɦɨɪɫɤɢɦ ɩɪɨɦɟɧɚɦɚ ɩɪɨɦɟɪɚ ɞɨ 4 cm, ɚɩɫɨɥɭɬɧɚ ɤɨɧɰɟɧɬɪɚɰɢʁɚ uKIM-1ɫɬɚɬɢɫɬɢɱɤɢ ɛɢɥɚ ɡɧɚɱɚʁɧɨ ɜɟʄɚ ɭ ɨɞɧɨɫɭ ɧɚ ɝɪɭɩɭ ɡɞɪɚɜɢɯ. ɇɚ ɬɚʁ ɧɚɱɢɧ ɨɞɪɟђɢɜɚʃɟ ɚɩɫɨɥɭɬɧɟ ɤɨɧɰɟɧɬɪɚɰɢʁɟ ɨɜɨɝ ɭɪɢɧɚɪɧɨɝ ɛɢɨɦɚɪɤɟɪɚ ɩɪɟɞɫɬɚɜʂɚɥɨ ɛɢ ɡɧɚɱɚʁɧɨ ɞɨɞɚɬɧɨ ɞɢʁɚɝɧɨɫɬɢɱɤɨ ɫɪɟɞɫɬɜɨ ɭ ɭɬɜɪђɢɜɚʃɭ ɩɪɢɪɨɞɟ ɦɚɥɢɯ ɬɭɦɨɪɫɤɢɯ ɩɪɨɦɟɧɚ ɢ ɨɞɥɭɤɟ ɨ ʃɢɯɨɜɨɦ ɥɟɱɟʃɭ. ɉɪɟɨɩɟɪɚɬɢɜɧɟ ɤɨɪɢɝɨɜɚɧɟ ɤɨɧɰɟɧɬɪɚɰɢʁɟ uKIM-1ɭ ɫɜɢɦ ɤɚɬɟɝɨɪɢʁɚɦɚ ɜɟɥɢɱɢɧɟ ɬɭɦɨɪɚ ɭ ɝɪɭɩɢ ɨɛɨɥɟɥɢɯ ɛɢɥɟ ɫɭ ɜɟʄɟ ɭ ɨɞɧɨɫɭ ɧɚ ɤɨɪɢɝɨɜɚɧɭ ɤɨɧɰɟɧɬɪɚɰɢʁɭ uKIM-1 ɭ ɝɪɭɩɢ ɡɞɪɚɜɢɯ ɢ ɬɚ ɪɚɡɥɢɤɚ ʁɟ ɛɢɥɚ ɫɬɚɬɢɫɬɢɱɤɢ ɡɧɚɱɚʁɧɨ ɜɟʄɚ (p=8.03*10-5). Ɇɟђɭɬɢɦ, ɩɨɪɟђɟʃɟɦ ɩɪɟɨɩɟɪɚɬɢɜɧɟ ɤɨɪɢɝɨɜɚɧɟ ɤɨɧɰɟɧɬɪɚɰɢʁɟ uKIM-1 ɩɪɟɦɚ ɤɚɬɟɝɨɪɢʁɢ ɜɟɥɢɱɢɧɟ ɬɭɦɨɪɚ ɭ ɝɪɭɩɢ ɨɛɨɥɟɥɢɯ ɢ ɤɨɪɢɝɨɜɚɧɟ ɤɨɧɰɟɧɬɪɚɰɢʁɟ uKIM-1 ɭ ɝɪɭɩɢ ɡɞɪɚɜɢɯ, ɞɨɛɢʁɟɧɚ ʁɟ ɫɬɚɬɢɫɬɢɱɤɢ ɡɧɚɱɚʁɧɨ ɜɟʄɚ ɤɨɧɰɟɧɬɪɚɰɢʁɚ uKIM-1 ɬɟɤ ɤɨɞ ɬɭɦɨɪɚ ɩɪɨɦɟɪɚ >7 cm. ɇɚɜɟɞɟɧɟ ɪɚɡɥɢɤɟ ɫɭ ɩɨɫɥɟɞɢɰɚ ɢɡɪɚɠɚɜɚʃɚ ɤɨɧɰɟɧɬɪɚɰɢʁɟ KIM-1 ɭ ɭɪɢɧɭ ɭ ɚɩɫɨɥɭɬɧɢɦ ɢ ɤɨɪɢɝɨɜɚɧɢɦ ɜɪɟɞɧɨɫɬɢɦɚ. ɇɚ ɨɫɧɨɜɭ ɞɨɫɚɞɚɲʃɢɯ ɢɫɩɢɬɢɜɚʃɚ, ɧɢ ɡɚ ʁɟɞɧɭ ɨɞ ɧɚɜɟɞɟɧɢɯ ɧɚɱɢɧɚ ɢɡɪɚɠɚɜɚʃɚ ɤɨɧɰɟɧɬɪɚɰɢʁɟ KIM-1 ɭ ɭɪɢɧɭ ɧɟ ɦɨɠɟ ɫɟ ɪɟʄɢ ɞɚ ʁɟ ɢɞɟɚɥɧɚ. ɉɪɢ ɬɭɦɚɱɟʃɭ ɚɩɫɨɥɭɬɧɢɯ ɤɨɧɰɟɧɬɪɚɰɢʁɚ ɧɟɤɨɝ ɭɪɢɧɚɪɧɨɝ ɛɢɨɦɚɪɤɟɪɚ, ɨɥɢɝɭɪɢʁɚ ʄɟ ɢɡɚɡɜɚɬɢ ɩɨɜɟʄɚʃɟ, ɚ ɩɨɥɢɭɪɢʁɚ ɫɧɢɠɟʃɟ ɚɩɫɨɥɭɬɧɢɯ ɤɨɧɰɟɧɬɪɚɰɢʁɚ ɛɢɨɦɚɪɤɟɪɚ, ɭɤɨɥɢɤɨ ɫɭ ɫɬɨɩɟ ɩɪɨɞɭɤɰɢʁɟ ɢ ɟɤɫɤɪɟɰɢʁɟ ɭɪɢɧɚɪɧɨɝ ɛɢɨɦɚɪɤɟɪɚ ɤɨɧɫɬɚɧɬɧɟ. ɇɨɪɦɚɥɢɡɚɰɢʁɚ ɤɨɧɰɟɧɬɪɚɰɢʁɟ ɭɪɢɧɚɪɧɨɝ ɛɢɨɦɚɪɤɟɪɚ ɩɪɟɦɚ ɤɨɧɰɟɧɬɪɚɰɢʁɢ ɤɪɟɚɬɢɧɢɧɚ ɭ ɭɪɢɧɭ ɭɡɢɦɚ ɭ ɨɛɡɢɪ ɪɚɡɥɢɤɟ ɭ ɜɨɥɭɦɟɧɭ ɢɡɥɭɱɟɧɨɝ ɭɪɢɧɚ. Ɇɟђɭɬɢɦ, ɩɪɢ ɧɨɪɦɚɥɢɡɚɰɢʁɢ ɦɨɪɚɦɨ ɭɡɟɬɢ ɭ ɨɛɡɢɪ ɫɬɨɩɭ ɟɤɫɤɪɟɰɢʁɟ ɤɪɟɚɬɢɧɢɧɚ ɨɞ ɫɬɪɚɧɟ ɛɭɛɪɟɝɚ. ɉɪɢ ɬɨɦɟ, ɜɪɟɞɧɨɫɬɢ ɭɪɢɧɚɪɧɟ ɟɤɫɤɪɟɰɢʁɟ ɤɪɟɚɬɢɧɢɧɚ ɦɨɝɭ ȾɂɋɄɍɋɂȳȺ 107 ɜɚɪɢɪɚɬɢ ɤɨɞ ɢɫɬɟ ɨɫɨɛɟ ɧɚ ɞɧɟɜɧɨɦ ɧɢɜɨɭ, ɩɪɢ ɱɟɦɭ ʁɟ ɜɪɟɞɧɨɫɬ ɫɟɪɭɦɫɤɨɝ ɤɪɟɚɬɢɧɢɧɚ ɫɬɚɛɢɥɧɚ. ɉɨɧɚɜʂɚɧɢɦ ɨɞɪɟђɢɜɚʃɟɦ ɤɨɧɰɟɧɬɪɚɰɢʁɟ ɤɪɟɚɬɢɧɢɧɚ ɭ 24-h ɫɤɭɩʂɟɧɢɦ ɜɨɥɭɦɟɧɢɦɚ ɭɪɢɧɚ, ɭɬɜɪђɟɧɨ ʁɟ ɞɚ ʁɟ ɢɧɬɪɚ-ɢɧɞɢɜɢɞɭɚɥɧɢ ɤɨɟɮɢɰɢʁɟɧɬ ɜɚɪɢʁɚɰɢʁɟ ɢɡɧɨɫɢɨ 10,5 ɞɨ 14,4%236. Ɉɫɬɚɥɟ ɫɬɭɞɢʁɟ ɫɭ ɬɚɤɨђɟ ɭɤɚɡɚɥɟ ɧɚ ɞɧɟɜɧɟ ɜɚɪɢʁɚɰɢʁɟ ɭ ɟɤɫɤɪɟɰɢʁɢ ɤɪɟɚɬɢɧɢɧɚ ɭ ɭɪɢɧɭ, ɤɚɨ ɢ ɜɚɪɢʁɚɛɢɥɧɨɫɬ ɭ ɟɤɫɤɪɟɰɢʁɢ ɨɞ ɱɚɫɚ ɞɨ ɱɚɫɚ237,238. Ɂɚɤʂɭɱɚɤ ɞɨɫɚɞɚɲʃɢɯ ɢɫɩɢɬɢɜɚʃɚ ɛɢ ɛɢɨ ɞɚ ɚɩɫɨɥɭɬɧɟ ɤɨɧɰɟɧɬɪɚɰɢʁɟ ɭɪɢɧɚɪɧɨɝ ɛɢɨɦɚɪɤɟɪɚ ɦɨɝɭ ɛɢɬɢ ɧɟɪɟɚɥɧɟ ɡɛɨɝ ɪɚɡɥɢɤɟ ɭ ɜɨɥɭɦɟɧɭ ɢɡɥɭɱɟɧɨɝ ɭɪɢɧɚ, ɞɨɤ ɤɨɧɰɟɧɬɪɚɰɢʁɟ ɤɨɪɢɝɨɜɚɧɟ ɩɪɟɦɚ ɤɨɧɰɟɧɬɪɚɰɢʁɢ ɭɪɢɧɚɪɧɨɝ ɤɪɟɚɬɢɧɢɧɚ ɦɨɝɭ ɛɢɬɢ ɧɟɪɟɚɥɧɟ ɡɛɨɝ ɪɚɡɥɢɤɟ ɭ ɫɬɨɩɢ ɟɤɫɤɪɟɰɢʁɟ ɤɪɟɚɬɢɧɢɧɚ. Ɉɞɪɟђɢɜɚʃɟ ɤɨɧɰɟɧɬɪɚɰɢʁɟ ɭɪɢɧɚɪɧɨɝ ɛɢɨɦɚɪɤɟɪɚ ɤɨʁɢ ɩɨɤɚɡɭʁɟ ɫɬɚɛɢɥɧɨɫɬ ɭ ɤɨɧɰɟɧɬɪɚɰɢʁɢ ɬɨɤɨɦ ɩɟɪɢɨɞɚ ɩɪɢɤɭɩʂɚʃɚ ɨɞ 24-h, ɤɚɨ ɲɬɨ ʁɟ ɞɨɤɚɡɚɧɨ ɡɚ KIM-1, ɨɛɟɡɛɟђɭʁɟ ɧɚʁɛɨʂɭ ɩɪɨɰɟɧɭ ɫɬɨɩɟ ɟɤɫɤɪɟɰɢʁɟ ɛɢɨɦɚɪɤɟɪɚ ɢ ɜɟɪɨɜɚɬɧɨ ɧɚʁɛɨʂɢ ɧɚɱɢɧ ɡɚ ɩɨɪɟђɟʃɟ ʃɟɝɨɜɟ ɤɨɧɰɟɧɬɪɚɰɢʁɟ ɢɡɦɟђɭ ɪɚɡɥɢɱɢɬɢɯ ɨɫɨɛɚ239. Ɇɟђɭɬɢɦ, ɩɨɫɬɨʁɟ ɨɡɛɢʂɧɚ ɩɪɚɤɬɢɱɧɚ ɨɝɪɚɧɢɱɟʃɚ ɡɚ ɩɪɢɤɭɩʂɚʃɟ 24-h ɭɪɢɧɚ, ɩɨɫɟɛɧɨ ɭ ɚɦɛɭɥɚɧɬɧɢɦ ɭɫɥɨɜɢɦɚ. Ɂɚɤʂɭɱɚɤ Waikar ɢ ɫɚɪ. ʁɟ ɞɚ ɛɢ ɢɫɬɪɚɠɢɜɚɱɢ ɬɪɟɛɚɥɨ ɩɪɢɥɢɤɨɦ ɬɭɦɚɱɟʃɚ ɧɨɪɦɚɥɢɡɨɜɚɧɢɯ ɬʁ. ɤɨɪɢɝɨɜɚɧɢɯ ɜɪɟɞɧɨɫɬɢ ɭɪɢɧɚɪɧɢɯ ɛɢɨɦɚɪɤɟɪɚ ɞɚ ɭɡɦɭ ɭ ɨɛɡɢɪ ɪɚɡɥɢɤɟ ɭ ɫɬɨɩɢ ɟɤɫɤɪɟɰɢʁɟ ɤɪɟɚɬɢɧɢɧɚ ɭ ɭɪɢɧɭ. Ɂɚɩɪɚɜɨ, ɭ ɧɟɤɢɦ ɫɥɭɱɚʁɟɜɢɦɚ ɧɨɪɦɚɥɢɡɚɰɢʁɚ ɦɨɠɟ ɥɚɠɧɨ ɩɨɜɟʄɚɬɢ ɞɢʁɚɝɧɨɫɬɢɱɤɢ ɡɧɚɱɚʁ ɛɢɨɦɚɪɤɟɪɚ, ɚ ɧɟɤɪɢɬɢɱɤɨ ɩɪɢɯɜɚɬɚʃɟ ɬɚɤɜɢɯ ɜɪɟɞɧɨɫɬɢ ɞɨɜɟɫɬɢ ɞɨ ɩɨɝɪɟɲɧɢɯ ɡɚɤʂɭɱɚɤɚ240. ɉɨɪɟђɟʃɟɦ ɚɩɫɨɥɭɬɧɢɯ ɢ ɤɨɪɢɝɨɜɚɧɢɯ ɤɨɧɰɟɧɬɪɚɰɢʁɚ uKIM-1 ɭ ɧɚɲɨʁ ɫɬɭɞɢʁɢ, ɩɨɤɚɡɚɥɢ ɫɦɨ ɞɚ ɨɛɟ ɜɪɟɞɧɨɫɬɢ ɢɦɚʁɭ ɞɢʁɚɝɧɨɫɬɢɱɤɢ ɡɧɚɱɚʁ ɡɚ ɞɟɬɟɤɰɢʁɭ ɫɄȻ, ɬʁ. ɨɛɟ ɜɪɟɞɧɨɫɬɢ ɫɭ ɛɢɥɟ ɫɬɚɬɢɫɬɢɱɤɢ ɡɧɚɱɚʁɧɨ ɜɢɲɟ ɩɪɟɨɩɟɪɚɬɢɜɧɨ ɭ ɨɞɧɨɫɭ ɧɚ ɩɨɫɬɨɩɟɪɚɬɢɜɧɟ ɜɪɟɞɧɨɫɬɢ, ɤɚɨ ɢ ɭ ɨɞɧɨɫɭ ɧɚ ɤɨɧɬɪɨɥɧɭ ɝɪɭɩɭ ɡɞɪɚɜɢɯ. 5.4. ɉɪɟɨɩɟɪɚɬɢɜɧɟ ɜɪɟɞɧɨɫɬɢ ɤɨɧɰɟɧɬɪɚɰɢʁɟ KIM-1 ɭ ɭɪɢɧɭ ɢ ɩɚɬɨɯɢɫɬɨɥɨɲɤɟ ɤɚɪɚɤɬɟɪɢɫɬɢɤɟ ɬɭɦɨɪɚ ɭ ɝɪɭɩɢ ɨɛɨɥɟɥɢɯ ɨɞ ɤɚɪɰɢɧɨɦɚ ɫɜɟɬɥɢɯ ʄɟɥɢʁɚ ɛɭɛɪɟɝɚ ɍ ɧɚɲɨʁ ɫɬɭɞɢʁɢ ɫɦɨ ɩɨɤɚɡɚɥɢ ɞɚ ɩɨɫɬɨʁɢ ɫɬɚɬɢɫɬɢɱɤɢ ɡɧɚɱɚʁɧɚ ɩɨɡɢɬɢɜɧɚ ɭɦɟɪɟɧɚ ɤɨɪɟɥɚɰɢʁɚ (ρ=0.498, p =0.001) ɢɡɦɟђɭ ɜɟɥɢɱɢɧɟ ɬɭɦɨɪɚ ɢ ɚɩɫɨɥɭɬɧɟ ɤɨɧɰɟɧɬɪɚɰɢʁɟ uKIM- 1, ɨɞɧɨɫɧɨ ɭɦɟɪɟɧɚ ɞɨ ɞɨɛɪɚ ɩɨɡɢɬɢɜɧɚ ɤɨɪɟɥɚɰɢʁɚ (ρ=0.541, p=0.003) ɢɡɦɟђɭ ɜɟɥɢɱɢɧɟ ɬɭɦɨɪɚ ɢ ɤɨɪɢɝɨɜɚɧɟ ɤɨɧɰɟɧɬɪɚɰɢʁɟ uKIM-1. ɇɚɲɢ ɪɟɡɭɥɬɚɬɢ ɫɟ ɩɨɤɥɚɩɚʁɭ ɫɚ ɪɟɡɭɥɬɚɬɢɦɚ ɞɪɭɝɢɯ ɫɬɭɞɢʁɚ. Han ɢ ɫɚɪ. ɫɭ ɩɨɤɚɡɚɥɢ ɞɚ ɩɨɫɬɨʁɢ ɞɢɪɟɤɬɧɚ ɩɨɜɟɡɚɧɨɫɬ ɢɡɦɟђɭ ɤɨɧɰɟɧɬɪɚɰɢʁɟ uKIM-1 ɢ ɜɟɥɢɱɢɧɟ ɬɭɦɨɪɚ145. Morrissey ɢ ɫɚɪ. ɫɭ ɭ ɫɜɨʁɨʁ ɫɬɭɞɢʁɢ ɞɨɤɚɡɚɥɢ ɞɚ ɩɨɫɬɨʁɢ ɩɨɡɢɬɢɜɧɚ ɤɨɪɟɥɚɰɢʁɚ ɢɡɦɟђɭ ɤɨɪɢɝɨɜɚɧɟ ɤɨɧɰɟɧɬɪɚɰɢʁɟ uKIM-1 ɢ ɜɟɥɢɱɢɧɟ ɬɭɦɨɪɚ, ɩɪɢ ɱɟɦɭ ʁɟ ɤɨɟɮɢɰɢʁɟɧɬ ɤɨɪɟɥɚɰɢʁɟ ɛɢɨ ɧɟɲɬɨ ɜɟʄɢ ɧɟɝɨ ɭ ɧɚɲɨʁ ɫɬɭɞɢʁɢ (ρ=0.66)146. ɇɚɭɩɪɨɬ ɬɨɦɟ, ɭ ɫɬɭɞɢʁɢ Shalabi ɢ ɫɚɪ. ɧɢʁɟ ɩɨɤɚɡɚɧɚ ɩɨɜɟɡɚɧɨɫɬ ɢɡɦɟђɭ ɞɢɦɟɧɡɢʁɚ ɬɭɦɨɪɚ ɢ ɤɨɧɰɟɧɬɪɚɰɢʁɟ uKIM-1, ɲɬɨ ʁɟ ɨɛʁɚɲʃɟɧɨ ɱɢʃɟɧɢɰɨɦ ɞɚ ʁɟ ɭ ɨɜɨʁ ɫɬɭɞɢʁɢ ɜɟʄɢɧɚ ɩɚɰɢʁɟɧɚɬɚ ɢɦɚɥɚ ɬɭɦɨɪɫɤɟ ɩɪɨɦɟɧɟ ɦɚʃɢɯ ɞɢɦɟɧɡɢʁɚ (4.57± 0.37 cm)147. Zhang ɢ ɫɚɪ., ɬɚɤɨђɟ ɧɢɫɭ ɧɚɲɥɢ ɩɨɜɟɡɚɧɨɫɬ ɢɡɦɟђɭ ɤɨɧɰɟɧɬɪɚɰɢʁɟ uKIM-1 ɢ ɜɟɥɢɱɢɧɟ ɬɭɦɨɪɚ, ɲɬɨ ɫɟ ɦɨɠɟ ɨɛʁɚɫɧɢɬɢ ɦɚɥɨɦ ɝɪɭɩɨɦ ɩɚɰɢʁɟɧɚɬɚ, ɭɤɭɩɧɨ 8, ɫɚ ɞɢʁɚɝɧɨɡɨɦ ɫɄȻ148. ȾɂɋɄɍɋɂȳȺ 108 Ʉɚɞɚ ɫɦɨ ɭɩɨɪɟɞɢɥɢ ɩɪɟɨɩɟɪɚɬɢɜɧɟ ɜɪɟɞɧɨɫɬɢ ɚɩɫɨɥɭɬɧɟ ɤɨɧɰɟɧɬɪɚɰɢʁɟ uKIM-1 ɩɪɟɦɚ ɤɚɬɟɝɨɪɢʁɢ ɜɟɥɢɱɢɧɟ ɬɭɦɨɪɚ (≤4 cm, 4.1-7 cm ɢ >7cm) ɞɨɛɢʁɟɧɚ ʁɟ ɫɬɚɬɢɫɬɢɱɤɢ ɡɧɚɱɚʁɧɚ ɪɚɡɥɢɤɚ ɢɡɦɟђɭ ɤɚɬɟɝɨɪɢʁɚ ɜɟɥɢɱɢɧɟ ɬɭɦɨɪɚ (p= 0.003). ȼɪɟɞɧɨɫɬ ɚɩɫɨɥɭɬɧɟ ɤɨɧɰɟɧɬɪɚɰɢʁɟ uKIM-1 ɪɚɫɥɚ ʁɟ ɫɚ ɜɟɥɢɱɢɧɨɦ ɬɭɦɨɪɚ, ɩɪɢ ɱɟɦɭ ɧɢʁɟ ɛɢɥɨ ɫɬɚɬɢɫɬɢɱɤɢ ɡɧɚɱɚʁɧɟ ɪɚɡɥɢɤɟ ɭ ɤɨɧɰɟɧɬɪɚɰɢʁɢ uKIM-1 ɢɡɦɟђɭ ɝɪɭɩɟ ɬɭɦɨɪɚ ≤4 cm ɢ ɬɭɦɨɪɚ ɞɢɦɟɧɡɢʁɚ 4.1-7 cm. Ɂɚɩɪɚɜɨ, ɪɚɡɥɢɤɚ ɭ ɫɪɟɞʃɨʁ ɜɪɟɞɧɨɫɬɢ ɚɩɫɨɥɭɬɧɟ ɤɨɧɰɟɧɬɪɚɰɢʁɟ uKIM-1 ɭ ɨɜɟ ɞɜɟ ɤɚɬɟɝɨɪɢʁɟ ɜɟɥɢɱɢɧɟ ɬɭɦɨɪɚ ɭ ɧɚɲɨʁ ɝɪɭɩɢ ɨɛɨɥɟɥɢɯ ɛɢɥɚ ʁɟ ɦɢɧɢɦɚɥɧɚ, ɱɢɦɟ ɫɟ ɩɨɜɟʄɚɜɚ ɡɧɚɱɚʁ uKIM-1 ɡɚ ɞɢʁɚɝɧɨɡɭ ɦɚɥɢɯ ɬɭɦɨɪɫɤɢɯ ɩɪɨɦɟɧɚ ɞɢɦɟɧɡɢʁɚ ɞɨ 4 cm. Ⱦɨɛɢʁɟɧɚ ʁɟ ɫɬɚɬɢɫɬɢɱɤɢ ɡɧɚɱɚʁɧɚ ɪɚɡɥɢɤɚ ɭ ɤɨɧɰɟɧɬɪɚɰɢʁɢ uKIM-1 ɬɟɤ ɭ ɤɚɬɟɝɨɪɢʁɢ ɬɭɦɨɪɚ >7 cm ɭ ɨɞɧɨɫɭ ɧɚ ɞɪɭɝɟ ɞɜɟ ɤɚɬɟɝɨɪɢʁɟ ɜɟɥɢɱɢɧɟ (≤4 cm ɢ 4.1-7 cm). Ʉɚɞɚ ɫɦɨ ɭɩɨɪɟɞɢɥɢ ɩɪɟɨɩɟɪɚɬɢɜɧɟ ɜɪɟɞɧɨɫɬɢ ɤɨɪɢɝɨɜɚɧɟ ɤɨɧɰɟɧɬɪɚɰɢʁɟuKIM-1ɢɡɦɟђɭ ɤɚɬɟɝɨɪɢʁɚ ɜɟɥɢɱɢɧɟ ɬɭɦɨɪɚ ɞɨɛɢʁɟɧɚ ʁɟ ɫɬɚɬɢɫɬɢɱɤɢ ɡɧɚɱɚʁɧɚ ɪɚɡɥɢɤɚ (p=0.001). ɉɨɪɟђɟʃɟɦ ɦɟђɭɫɨɛɧɨ ɤɚɬɟɝɨɪɢʁɚ ɜɟɥɢɱɢɧɟ ɬɭɦɨɪɚ, ɬɚɤɨђɟ ʁɟ ɩɨɤɚɡɚɧɚ ɫɬɚɬɢɫɬɢɱɤɢ ɡɧɚɱɚʁɧɨ ɜɟʄɚ ɤɨɧɰɟɧɬɪɚɰɢʁɚ uKIM-1 ɭ ɤɚɬɟɝɨɪɢʁɢ ɬɭɦɨɪɚ >7cm ɭ ɨɞɧɨɫɭ ɧɚ ɞɪɭɝɟ ɞɜɟ ɤɚɬɟɝɨɪɢʁɟ ɜɟɥɢɱɢɧɟ ɬɭɦɨɪɚ. ɂɧɬɟɪɟɫɚɧɬɧɨ ʁɟ ɞɚ ʁɟ ɫɪɟɞʃɚ ɜɪɟɞɧɨɫɬ ɤɨɪɢɝɨɜɚɧɟ ɤɨɧɰɟɧɬɪɚɰɢʁɟ uKIM-1 ɭ ɤɚɬɟɝɨɪɢʁɢ ɬɭɦɨɪɚ ɜɟɥɢɱɢɧɟ ≤4 cm ɛɢɥɚ ɧɟɡɧɚɬɧɨ ɜɟʄɚ ɭ ɨɞɧɨɫɭ ɧɚ ɜɪɟɞɧɨɫɬ ɭ ɝɪɭɩɢ ɬɭɦɨɪɚ ɜɟɥɢɱɢɧɟ 4.1-7 cm ɚɥɢ ɛɟɡ ɫɬɚɬɢɫɬɢɱɤɟ ɡɧɚɱɚʁɧɨɫɬɢ. Ɉɜɚ ɪɚɡɥɢɤɚ ɫɟ ɦɨɠɟ ɨɛʁɚɫɧɢɬɢ ɪɚɡɥɢɤɨɦ ɭ ɤɨɥɢɱɢɧɢ ɢɡɥɭɱɟɧɨɝ KIM-1 ɨɞ ɫɬɪɚɧɟ ɬɭɦɨɪɚ ɫɥɢɱɧɟ ɜɟɥɢɱɢɧɟ ɢ ɫɬɚɞɢʁɭɦɚ, ɬʁ. ɜɚɪɢʁɚɰɢʁɨɦ ɭ ɤɨɥɢɱɢɧɢ KIM-1 ɤɨʁɟ ɥɭɱɟ ɩɨʁɟɞɢɧɚɱɧɟ ɬɭɦɨɪɫɤɟ ʄɟɥɢʁɟ, ɲɬɨ ʁɟ ɞɟɥɨɦ ɨɛʁɚɲʃɟɧɨ ɭ ɫɬɭɞɢʁɢ Zhang ɢ ɫɚɪ. Ʉɨɥɢɱɢɧɚ KIM-1 ɦɨɠɟ ɡɚɜɢɫɢɬɢ ɨɞ ɧɟɤɨɥɢɤɨ ɮɚɤɬɨɪɚ: ɩɪɨɞɭɤɬɢɜɧɨɫɬɢ KIM-1 ɨɞ ɫɬɪɚɧɟ ɩɨʁɟɞɢɧɚɱɧɢɯ ɬɭɦɨɪɫɤɢɯ ʄɟɥɢʁɚ, ɜɟɥɢɱɢɧɟ ɬɭɦɨɪɚ ɢ ɩɭɬɚ ʃɟɝɨɜɨɝ ɥɭɱɟʃɚ ɭ ɭɪɢɧ. ɉɨɫɬɨʁɟ ɞɜɚ ɧɚɱɢɧɚ ɤɨʁɢɦ KIM-1 ɩɨɪɟɤɥɨɦ ɨɞ ʄɟɥɢʁɚ ɤɚɪɰɢɧɨɦɚ ɫɜɟɬɥɢɯ ʄɟɥɢʁɚ ɦɨɠɟ ɛɢɬɢ ɢɡɥɭɱɟɧ ɭ ɭɪɢɧ. ȳɟɞɚɧ ɨɞ ʃɢɯ ʁɟ ɝɥɨɦɟɪɭɥɫɤɨɦ ɮɢɥɬɪɚɰɢʁɨɦ, ɚ ɞɪɭɝɢ ɬɭɦɨɪɫɤɨɦ ɢɧɜɚɡɢʁɨɦ ɫɚɛɢɪɧɨɝ ɫɢɫɬɟɦɚ. Ɍɟɨɪɟɬɫɤɢ, ɨɞɰɟɩʂɟɧɢ ɫɨɥɭɛɢɥɧɢ KIM-1 ɩɪɨɬɟɢɧ, ɱɢʁɚ ɦɨɥɟɤɭɥɫɤɚ ɬɟɠɢɧɚ ɢɡɧɨɫɢ 90 kDa ɢ ɩɪɢɩɚɞɚ ɩɪɨɬɟɢɧɢɦɚ ɫɪɟɞʃɟ ɜɟɥɢɱɢɧɟ, ɦɨɠɟ ɫɟ ɞɟɥɨɦ ɮɢɥɬɪɢɪɚɬɢ ɤɪɨɡ ɝɥɨɦɟɪɭɥɫɤɭ ɛɚɡɚɥɧɭ ɦɟɦɛɪɚɧɭ, ɩɪɢ ɱɟɦɭ ʁɟɞɧɚ ɤɨɥɢɱɢɧɚ ɮɢɥɬɪɨɜɚɧɨɝ KIM-1 ɦɨɠɟ ɛɢɬɢ ɪɟɚɩɫɨɪɛɨɜɚɧɚ ɧɚ ɧɢɜɨɭ ɩɪɨɤɫɢɦɚɥɧɢɯ ɬɭɛɭɥɚ ɡɚɜɢɫɧɨ ɨɞ ɤɨɥɢɱɢɧɟ ɮɢɥɬɪɚɬɚ ɭ ɭɫɥɨɜɢɦɚ ɨɱɭɜɚɧɟ ɛɭɛɪɟɠɧɟ ɮɭɧɤɰɢʁɟ. ȳɨɲ ɭɜɟɤ ɧɢʁɟ ʁɚɫɧɨ ɡɚɲɬɨ ɧɟɤɢ ɤɚɪɰɢɧɨɦɢ ɛɭɛɪɟɝɚ ɥɭɱɟ ɦɚʃɭ, ɚ ɧɟɤɢ ɜɟʄɭ ɤɨɥɢɱɢɧɭ uKIM-1, ɩɪɢ ɱɟɦɭ ɫɭ ɫɥɢɱɧɟ ɜɟɥɢɱɢɧɟ ɢ ɫɬɚɞɢʁɭɦɚ148. ɇɚʁɜɟʄɢ ɩɪɨɰɟɧɚɬ ɩɚɰɢʁɟɧɚɬɚ ɭ ɧɚɲɨʁ ɫɬɭɞɢʁɢ ɢɦɚɨ ʁɟ G2 (78,05%) ɢ G3 (19,51%) ɝɪɚɞɭɫ ɬɭɦɨɪɚ, ɞɨɤ ʁɟ ɫɚɦɨ ʁɟɞɚɧ (2,44%) ɩɚɰɢʁɟɧɬ ɢɦɚɨ ɢɦɚɨ G4 ɝɪɚɞɭɫ. ɂɫɬɢ ɩɚɰɢʁɟɧɬ ɢɦɚɨ ʁɟ ɡɧɚɤɟ ɫɚɪɤɨɦɚɬɨɢɞɧɟ ɢ ɪɚɛɞɨɢɞɧɟ ɬɪɚɧɫɮɨɪɦɚɰɢʁɟ. ɇɢʁɟɞɚɧ ɩɚɰɢʁɟɧɬ ɧɢʁɟ ɢɦɚɨ G1 ɯɢɫɬɨɥɨɲɤɢ ɝɪɚɞɭɫ. ɉɨɪɟђɟʃɟɦ ɩɪɟɨɩɟɪɚɬɢɜɧɢɯ ɜɪɟɞɧɨɫɬɢ ɚɩɫɨɥɭɬɧɢɯ ɤɨɧɰɟɧɬɪɚɰɢʁɚ uKIM-1 ɢ ɯɢɫɬɨɥɨɲɤɨɝ ɝɪɚɞɭɫɚ ɬɭɦɨɪɚ, ɞɨɛɢʁɟɧɚ ʁɟ ɞɢɪɟɤɬɧɚ ɩɨɜɟɡɚɧɨɫɬ, ɬʁ ɤɨɧɰɟɧɬɪɚɰɢʁɚ ʁɟ ɪɚɫɥɚ ɫɚ ɩɨɜɟʄɚʃɟɦ ɝɪɚɞɭɫɚ ɬɭɦɨɪɚ. Ⱦɨɛɢʁɟɧɚ ʁɟ ɫɬɚɬɢɫɬɢɱɤɢ ɡɧɚɱɚʁɧɚ ɪɚɡɥɢɤɚ (p=0.003)ɭ ɩɪɟɨɩɟɪɚɬɢɜɧɢɦ ɜɪɟɞɧɨɫɬɢɦɚ uKIM-1.0 ɢɡɦɟђɭ ɤɚɬɟɝɨɪɢʁɚɯɢɫɬɨɥɨɲɤɨɝ ɝɪɚɞɭɫɚ ɬɭɦɨɪɚ. ɉɪɢ ɬɨɦɟ, ɩɪɟɨɩɟɪɚɬɢɜɧɟ ɜɪɟɞɧɨɫɬɢ uKIM-1 ɭ ɝɪɭɩɢ ɬɭɦɨɪɚ ɯɢɫɬɨɥɨɲɤɨɝ ɝɪɚɞɭɫɚ G3 ɛɢɥɟ ɫɭ ɫɬɚɬɢɫɬɢɱɤɢ ɡɧɚɱɚʁɧɨ ɜɢɲɟ (p*= 0.0017) ɭ ɨɞɧɨɫɭ ɧɚ ɜɪɟɞɧɨɫɬɢ uKIM-1 ɭ ɝɪɭɩɢ ɬɭɦɨɪɚ ɝɪɚɞɭɫɚ G2. ɉɨɪɟђɟʃɟɦ ɤɨɪɢɝɨɜɚɧɢɯ ɜɪɟɞɧɨɫɬɢ uKIM-1 ɢɡɦɟђɭG2 ɢ G3 ɯɢɫɬɨɥɨɲɤɨɝ ɝɪɚɞɭɫɚ ɬɭɦɨɪɚ, ɬɚɤɨђɟ ʁɟ ɞɨɛɢʁɟɧɚ ɫɬɚɬɢɫɬɢɱɤɢ ɡɧɚɱɚʁɧɨ ɜɢɲɚ ɤɨɧɰɟɧɬɪɚɰɢʁɚ ȾɂɋɄɍɋɂȳȺ 109 (p*=0.001) uKIM-1 ɭ ɝɪɭɩɢ ɬɭɦɨɪɚ G3 ɯɢɫɬɨɥɨɲɤɨɝ ɝɪɚɞɭɫɚ. ȼɪɟɞɧɨɫɬ uKIM-1 ɤɨɞ ɩɚɰɢʁɟɧɬɚ ɫɚ ɬɭɦɨɪɨɦ ɯɢɫɬɨɥɨɲɤɨɝ ɝɪɚɞɭɫɚ G4 ɛɢɥɚ ʁɟ ɜɢɲɚ ɭ ɨɞɧɨɫɭ ɧɚ ɜɪɟɞɧɨɫɬ uKIM-1 ɭ ɝɪɭɩɢ ɬɭɦɨɪɚ ɝɪɚɞɭɫɚ G3, ɲɬɨ ɧɢʁɟ ɞɨɛɢʁɟɧɨ ɡɚ ɤɨɪɢɝɨɜɚɧɭ ɜɪɟɞɧɨɫɬ uKIM-1. ɋ ɨɛɡɢɪɨɦ ɞɚ ʁɟ ɫɚɦɨ ʁɟɞɚɧ ɩɚɰɢʁɟɧɬ ɢɦɚɨ G4 ɯɢɫɬɨɥɨɲɤɢ ɝɪɚɞɭɫ,ɧɚɥɚɡ ɫɟ ɧɟ ɦɨɠɟ ɫɦɚɬɪɚɬɢ ɪɟɥɟɜɚɧɬɧɢɦ. Ɋɟɡɭɥɬɚɬɢ ɧɚɲɟ ɫɬɭɞɢʁɟ ɫɭ ɩɨɤɚɡɚɥɢ ɞɚ ʁɟ ɤɨɧɰɟɧɬɪɚɰɢʁɚ uKIM-1 ɫɪɚɡɦɟɪɧɚ ɯɢɫɬɨɥɨɲɤɨɦ ɝɪɚɞɭɫɭ ɬɭɦɨɪɚ. Ⱦɪɭɝɢ ɚɭɬɨɪɢ ɧɢɫɭ ɧɚɲɥɢ ɫɢɝɧɢɮɢɤɚɧɬɧɭ ɩɨɜɟɡɚɧɨɫɬ ɢɡɦɟђɭ ɤɨɧɰɟɧɬɪɚɰɢʁɟ uKIM-1ɢɝɪɚɞɭɫɚ ɬɭɦɨɪɚ147, 148 . Ⱥɭɬɨɪɢ ɞɪɭɝɟ ɞɜɟ ɫɬɭɞɢʁɟ ɧɢɫɭ ɢɫɩɢɬɢɜɚɥɢ ɩɨɜɟɡɚɧɨɫɬ ɢɡɦɟђɭ ɤɨɧɰɟɧɬɪɚɰɢʁɟ uKIM-1 ɢ ɝɪɚɞɭɫɚ ɬɭɦɨɪɚ145, 146. ɍ ɧɚɲɨʁ ɫɬɭɞɢʁɢ ɧɚʁɜɟʄɢ ɩɪɨɰɟɧɚɬ ɩɚɰɢʁɟɧɚɬɚ ɢɦɚɨ ʁɟ pT3ɚ, 34% ɢ pT1ɚ ɫɬɚɞɢʁɭɦ ɬɭɦɨɪɚ 32%, pT1ɛ ɛɢɨ ʁɟ ɡɚɫɬɭɩʂɟɧ ɤɨɞ 27% ɨɩɟɪɢɫɚɧɢɯ, ɚ pT2a ɤɨɞ 7% ɨɩɟɪɢɫɚɧɢɯ. Ɉɫɬɚɥɢ ɩɚɬɨɥɨɲɤɢ ɫɬɚɞɢʁɭɦɢ ɬɭɦɨɪɚ ɧɢɫɭ ɛɢɥɢ ɡɚɫɬɭɩʂɟɧɢ ɭ ɧɚɲɨʁ ɫɬɭɞɢʁɢ. ɉɨɪɟђɟʃɟɦ ɩɪɟɨɩɟɪɚɬɢɜɧɢɯ ɚɩɫɨɥɭɬɧɢɯ ɤɨɧɰɟɧɬɪɚɰɢʁɚ uKIM-1 ɢ ɩɚɬɨɥɨɲɤɢɯ ɫɬɚɞɢʁɭɦɚ ɬɭɦɨɪɚ, ɞɨɛɢʁɟɧɚ ʁɟ ɫɬɚɬɢɫɬɢɱɤɢ ɡɧɚɱɚʁɧɚ ɪɚɡɥɢɤɚ (p=0.0004) ɢɡɦɟђɭ ɤɚɬɟɝɨɪɢʁɚ ɩɚɬɨɥɨɲɤɢɯ ɫɬɚɞɢʁɭɦɚ. ɂɫɬɢ ɪɟɡɭɥɬɚɬɢ ɞɨɛɢʁɟɧɢ ɫɭ ɢ ɡɚ ɤɨɪɢɝɨɜɚɧɭ ɜɪɟɞɧɨɫɬ uKIM-1 (p= 5.42*10-5). ɉɨɪɟђɟʃɟɦ ɩɚɪɨɜɚ ɩɚɬɨɥɨɲɤɢɯ ɫɬɚɞɢʁɭɦɚ ɬɭɦɨɪɚ, ɞɨɛɢɥɢ ɫɦɨ ɫɬɚɬɢɫɬɢɱɤɢ ɡɧɚɱɚʁɧɨ ɜɢɲɟ ɩɪɟɨɩɟɪɚɬɢɜɧɟ ɜɪɟɞɧɨɫɬɢ ɢ ɚɩɫɨɥɭɬɧɟ ɢ ɤɨɪɢɝɨɜɚɧɟ ɤɨɧɰɟɧɬɪɚɰɢʁɟ uKIM-1 ɭ ɝɪɭɩɢ ɬɭɦɨɪɚ ɫɬɚɞɢʁɭɦɚ pT3ɚ ɭ ɨɞɧɨɫɭ ɧɚ ɫɬɚɞɢʁɭɦɟ pT1ɚ ɢ pT1ɛ. ɋ ɨɛɡɢɪɨɦ ɞɚ ɧɚ pT3ɚ ɫɬɚɞɢʁɭɦ, ɩɨɪɟɞ ɞɢɦɟɧɡɢʁɚ ɬɭɦɨɪɚ ɭɬɢɱɟ ɢ ɲɢɪɟʃɟ ɬɭɦɨɪɚ ɭ ɪɟɧɚɥɧɭ ɜɟɧɭ ɢɥɢ ʃɟɧɟ ɫɟɝɦɟɧɬɧɟ, ɦɢɲɢʄɧɟ ɝɪɚɧɟ ɢɥɢ ɩɟɪɢɪɟɧɚɥɧɨ ɢ/ɢɥɢ ɦɚɫɧɨ ɬɤɢɜɨ ɛɭɛɪɟɠɧɨɝ ɫɢɧɭɫɚ, ɦɨɠɟɦɨ ɡɚɤʂɭɱɢɬɢ ɞɚ ɡɚɯɜɚɬɚʃɟ ɧɚɜɟɞɟɧɢɯ ɫɬɪɭɤɬɭɪɚ ɦɨɠɟ ɛɢɬɢ ɩɨɜɟɡɚɧɨ ɫɚ ɡɧɚɱɚʁɧɨ ɜɟʄɨɦ ɤɨɧɰɟɧɬɪɚɰɢʁɨɦ uKIM-1. ɇɚɲɢ ɪɟɡɭɥɬɚɬɢ ɫɟ ɩɨɤɥɚɩɚʁɭ ɫɚ ɪɟɡɭɥɬɚɬɢɦɚ Morrissey ɢ ɫɚɪ., ɤɨʁɢ ɫɭ ɞɨɤɚɡɚɥɢ ɞɚ ɫɚ ɩɨɜɟʄɚʃɟɦ ɩɚɬɨɥɨɲɤɨɝ ɫɬɚɞɢʁɭɦɚ ɬɭɦɨɪɚ ɡɧɚɱɚʁɧɨ ɪɚɫɬɟ ɤɨɧɰɟɧɬɪɚɰɢʁɚ uKIM-1146. Ⱥɭɬɨɪɢ ɞɪɭɝɢɯ ɫɬɭɞɢʁɚ ɧɢɫɭ ɢɫɩɢɬɢɜɚɥɢ ɩɨɪɟђɟʃɟ ɤɨɧɰɟɧɬɪɚɰɢʁɟ uKIM-1 ɢ ɩɚɬɨɥɨɲɤɨɝ ɫɬɚɞɢʁɭɦɚ ɬɭɦɨɪɚ. ɍ ɧɚɲɟɦ ɢɫɩɢɬɢɜɚʃɭ ɫɩɪɨɜɟɥɢ ɫɦɨ ɩɨɪɟђɟʃɟ ɜɪɟɞɧɨɫɬɢ ɚɩɫɨɥɭɬɧɟ ɤɨɧɰɟɧɬɪɚɰɢʁɟ uKIM-1 ɩɪɟ ɨɩɟɪɚɰɢʁɟɭ ɨɞɧɨɫɭ ɧɚ ɤɚɬɟɝɨɪɢʁɟ ɥɢɦɮɧɨ-ɜɚɫɤɭɥɚɪɧɟ ɬɭɦɨɪɫɤɟ ɢɧɜɚɡɢʁɟ (Ʌȼɂ) ɢ ɞɨɤɚɡɚɥɢ ɞɚ ɩɨɫɬɨʁɢ ɫɬɚɬɢɫɬɢɱɤɢ ɡɧɚɱɚʁɧɚ ɪɚɡɥɢɤɚ (p=0.008) ɢɡɦɟђɭ ɤɚɬɟɝɨɪɢʁɚ. ɋɬɚɬɢɫɬɢɱɤɢ ɡɧɚɱɚʁɧɚ ɪɚɡɥɢɤɚ (p=0.0002) ɞɨɛɢʁɟɧɚ ʁɟ ɢ ɡɚ ɤɨɪɢɝɨɜɚɧɟ ɤɨɧɰɟɧɬɪɚɰɢʁɟ uKIM- 1. ɉɨɪɟђɟʃɟɦ ɚɩɫɨɥɭɬɧɢɯ ɢ ɤɨɪɢɝɨɜɚɧɢɯ ɤɨɧɰɟɧɬɪɚɰɢʁɚ uKIM-1 ɢɡɦɟђɭ ɩɚɪɨɜɚ ɤɚɬɟɝɨɪɢʁɚ Ʌȼɂ, ɞɨɛɢʁɟɧɚ ʁɟ ɫɬɚɬɢɫɬɢɱɤɢ ɡɧɚɱɚʁɧɨ ɜɢɲɚ ɜɪɟɞɧɨɫɬ (p*= 0.0001) ɭ ɝɪɭɩɢ ɩɚɰɢʁɟɧɚɬɚ ɫɚ Ʌȼɂ (ɤɚɬɟɝɨɪɢʁɚ L1V1) ɭ ɨɞɧɨɫɭ ɧɚ ɝɪɭɩɭ ɛɟɡ Ʌȼɂ (ɤɚɬɟɝɨɪɢʁɚ L0V0) ɢ ɧɚ ɝɪɭɩɭ ɫɚ ɬɭɦɨɪɫɤɨɦ ɥɢɦɮɧɨɦ ɢɥɢ ɜɚɫɤɭɥɚɪɧɨɦ ɢɧɜɚɡɢʁɨɦ (ɤɚɬɟɝɨɪɢʁɚ L0V1 ɨɞɧɨɫɧɨ L1V0). Ɋɟɡɭɥɬɚɬɢ ɧɚɲɟ ɫɬɭɞɢʁɟ ɫɭ ɩɨɤɚɡɚɥɢ ɞɚ ʁɟ ɤɨɧɰɟɧɬɪɚɰɢʁɚ uKIM-1 ɫɪɚɡɦɟɪɧɚ ɩɨɫɬɨɩɟɪɚɬɢɜɧɨɦ TNM ɫɬɚɞɢʁɭɦɭ. ɉɨɪɟђɟʃɟɦ ɜɪɟɞɧɨɫɬɢ ɚɩɫɨɥɭɬɧɟ ɢ ɤɨɪɢɝɨɜɚɧɟ ɤɨɧɰɟɧɬɪɚɰɢʁɟ uKIM-1 ɩɪɟ ɨɩɟɪɚɰɢʁɟɭ ɨɞɧɨɫɭ ɧɚ ɤɚɬɟɝɨɪɢʁɟ ɩɨɫɬɨɩɟɪɚɬɢɜɧɨɝ TNM ɫɬɚɞɢʁɭɦɚ, ɞɨɤɚɡɚɥɢ ɫɦɨ ɞɚ ɩɨɫɬɨʁɢ ɫɬɚɬɢɫɬɢɱɤɢ ɡɧɚɱɚʁɧɚ ɪɚɡɥɢɤɚ ɭ ɤɨɧɰɟɧɬɪɚɰɢʁɢ uKIM- 1ɢɡɦɟђɭ ɪɚɡɥɢɱɢɬɢɯ TNM ɫɬɚɞɢʁɭɦɚ. ȼɪɟɞɧɨɫɬɢ ɤɨɧɰɟɧɬɪɚɰɢʁɟ uKIM-1 ɪɚɫɥɟ ɫɭ ɫɪɚɡɦɟɪɧɨ ɩɨɜɟʄɚʃɭ TNM ɫɬɚɞɢʁɭɦɚ, ɩɪɢ ɱɟɦɭ ʁɟ ɩɨɪɟђɟʃɟɦ ɩɚɪɨɜɚ ɤɚɬɟɝɨɪɢʁɚ TNM ɫɬɚɞɢʁɭɦɚ ɞɨɛɢʁɟɧɚ ɫɬɚɬɢɫɬɢɱɤɢ ɡɧɚɱɚʁɧɚ ɪɚɡɥɢɤɚ ɭ ɩɪɟɨɩɟɪɚɬɢɜɧɢɦ ɤɨɧɰɟɧɬɪɚɰɢʁɚɦɚ uKIM-1 ɫɚɦɨ ɢɡɦɟђɭ ɩɚɰɢʁɟɧɚɬɚ ɭ ɩɪɜɨɦ ɢ ɬɪɟʄɟɦ TNM ɫɬɚɞɢʁɭɦɭ. ɋ ɨɛɡɢɪɨɦ ɞɚ ʁɟ ɦɚɥɢ ɛɪɨʁ ɩɚɰɢʁɟɧɚɬɚ ȾɂɋɄɍɋɂȳȺ 110 ɭ ɧɚɲɨʁ ɫɬɭɞɢʁɢ, ɭɤɭɩɧɨ 2, ɢɦɚɨ ɱɟɬɜɪɬɢ TNM ɫɬɚɞɢʁɭɦ, ɧɢʁɟ ɞɨɛɢʁɟɧɚ ɫɬɚɬɢɫɬɢɱɤɢ ɡɧɚɱɚʁɧɚ ɪɚɡɥɢɤɚ ɭ ɤɨɧɰɟɧɬɪɚɰɢʁɚɦɚ ɢɡɦɟђɭ ɩɚɰɢʁɟɧɚɬɚ ɭ ɩɪɜɨɦ ɢ ɱɟɬɜɪɬɨɦ TNM ɫɬɚɞɢʁɭɦɭ. ɉɪɟɦɚ ɧɚɲɢɦ ɫɚɡɧɚʃɢɦɚ, ɧɟ ɩɨɫɬɨʁɟ ɫɬɭɞɢʁɟ ɤɨʁɟ ɫɭ ɩɨɪɟɞɢɥɟ ɤɨɧɰɟɧɬɪɚɰɢʁɚ uKIM-1 ɫɚ ɤɚɬɟɝɨɪɢʁɚɦɚ ɥɢɦɮɧɨ-ɜɚɫɤɭɥɚɪɧɟ ɢɧɜɚɡɢʁɟ ɢ TNM ɫɬɚɞɢʁɭɦɚ. 5.5. Ʉɨɧɰɟɧɬɪɚɰɢʁɚ KIM-1 ɭ ɭɪɢɧɭ ɩɚɰɢʁɟɧɚɬɚ ɥɟɱɟɧɢɯ ɪɚɞɢɤɚɥɧɨɦ ɢ ɩɚɪɰɢʁɚɥɧɨɦ ɧɟɮɪɟɤɬɨɦɢʁɨɦ Ɍɨɤɨɦ ɯɢɪɭɪɲɤɨɝ ɢɡɜɨђɟʃɚ ɩɚɪɰɢʁɚɥɧɟ ɧɟɮɪɟɤɬɨɦɢʁɟ (ɉɇ), ɡɛɨɝ ɩɪɨɥɚɡɧɨɝ ɩɪɟɫɬɚɧɤɚ ɞɨɬɨɤɚ ɤɪɜɢ ɢɡ ɪɟɧɚɥɧɟ ɚɪɬɟɪɢʁɟ, ɦɨɠɟ ɞɨʄɢ ɞɨ ɢɫɯɟɦɢʁɫɤɨɝ ɛɭɛɪɟɠɧɨɝ ɨɲɬɟʄɟʃɚ ɢ ɪɚɡɜɨʁɚ ɚɤɭɬɧɟ ɛɭɛɪɟɠɧɟ ɢɧɫɭɮɢɰɢʁɟɧɰɢʁɟ217. ɂɫɩɢɬɢɜɚʃɚ ɫɭ ɩɨɤɚɡɚɥɟ ɞɚ ɜɪɟɦɟ ɬɪɚʁɚʃɚ ɢɫɯɟɦɢʁɟ ɬɨɤɨɦ ɉɇ ɩɪɟɞɫɬɚɜʂɚ ʁɟɞɚɧ ɨɞ ɧɚʁɡɧɚɱɚʁɧɢʁɢɯ ɮɚɤɬɨɪɚ ɡɚ ɨɩɨɪɚɜɚɤ ɛɭɛɪɟɠɧɟ ɮɭɧɤɰɢʁɟ ɭ ɩɨɫɬɨɩɟɪɚɬɢɜɧɨɦ ɩɟɪɢɨɞɭ241. ɂɡ ɬɨɝ ɪɚɡɥɨɝɚ ɩɪɟɜɟɧɰɢʁɚ ɨɲɬɟʄɟʃɚ ɮɭɧɤɰɢɨɧɚɥɧɨɝ ɬɤɢɜɚ ɛɭɛɪɟɝɚ ɬɨɤɨɦ ɉɇ ʁɟ ɨɞ ɤʂɭɱɧɨɝ ɡɧɚɱɚʁɚ ɡɚ ɩɪɟɠɢɜʂɚɜɚʃɟ ɨɜɢɯ ɛɨɥɟɫɧɢɤɚ. Ɍɟɠɢɧɚ ɛɭɛɪɟɠɧɨɝ ɨɲɬɟʄɟʃɚ ɦɨɠɟ ɫɟ ɤɜɚɧɬɢɬɚɬɢɜɧɨ ɨɞɪɟɞɢɬɢ ɦɟɪɟʃɟɦ ɭɪɢɧɚɪɧɢɯ ɩɪɨɬɟɢɧɚ, ɤɨʁɢ ɩɪɟɞɫɬɚɜʂɚʁɭ ɪɚɧɟ ɢ ɫɟɧɡɢɬɢɜɧɟ ɩɪɟɞɢɤɬɨɪɟ ɪɚɡɜɨʁɚ ɚɤɭɬɧɨɝ ɛɭɛɪɟɠɧɨɝ ɨɲɬɟʄɟʃɚ. Ɉɞ ɩɨɫɟɛɧɨɝ ɡɧɚɱɚʁɚ ɫɭ ɫɟ ɢɡɞɜɨʁɢɥɚ ɞɜɚ ɭɪɢɧɚɪɧɚ ɦɚɪɤɟɪɚ, ɧɟɭɬɪɨɮɢɥɧɚ ɠɟɥɚɬɢɧɚɡɚ ɭɞɪɭɠɟɧɚ ɫɚ ɥɢɩɨɤɚɥɢɧɨɦ (ɟɧɝɥ. ɫɤɪ. NGAL-neutrophil gelatinase-associated lipocalin) ɢ KIM-1. ɍ ɤɥɢɧɢɱɤɢɦ ɫɬɭɞɢʁɚɦɚ ʁɟ ɩɨɤɚɡɚɧɨ ɞɚ ɫɭ ɩɥɚɡɦɚ ɢɥɢ ɭɪɢɧɚɪɧɟ ɤɨɧɰɟɧɬɪɚɰɢʁɟ ɨɜɢɯ ɛɢɨɦɚɪɤɟɪɚ ɩɨɪɚɫɥɟ ɧɟɤɨɥɢɤɨ ɱɚɫɨɜɚ ɧɚɤɨɧ ɚɤɭɬɧɨɝ ɛɭɛɪɟɠɧɨɝ ɨɲɬɟʄɟʃɚ ɪɚɡɥɢɱɢɬɟ ɟɬɢɨɥɨɝɢʁɟ: ɫɪɱɚɧɚ ɫɥɚɛɨɫɬ, ɤɚɪɞɢɨɩɭɥɦɨɧɚɥɧɢ by-pass, ɩɪɢɦɟɧɚ ɧɟɮɪɨɬɨɤɫɢɱɧɢɯ ɥɟɤɨɜɚ ɢɥɢ ɪɚɞɢɨɤɨɧɬɪɚɫɬɧɢɯ ɫɪɟɞɫɬɚɜɚ242, 243, 244. ɉɪɟɦɚ ɧɚɲɢɦ ɫɚɡɧɚʃɢɦɚ, ɫɬɭɞɢʁɚ Abassi ɢ ɫɚɪ. ɩɪɟɞɫɬɚɜʂɚ ʁɟɞɢɧɭ ɞɨ ɫɚɞɚ ɨɛʁɚɜʂɟɧɭ ɫɬɭɞɢʁɭ ɨ ɩɨɪɟђɟʃɭ ɤɨɧɰɟɧɬɪɚɰɢʁɚuKIM-1 ɤɨɞ ɩɚɰɢʁɟɧɚɬɚ ɩɪɟ ɢ ɭ ɪɚɡɥɢɱɢɬɢɦ ɜɪɟɦɟɧɫɤɢɦ ɢɧɬɟɪɜɚɥɢɦɚ ɧɚɤɨɧ ɩɚɪɰɢʁɚɥɧɟ ɧɟɮɪɟɤɬɨɦɢʁɟ. ɍ ɫɜɨʁɨʁ ɫɬɭɞɢʁɢ ɨɧɢ ɫɭ ɩɨɪɟɞɢɥɢ ɭɪɢɧɚɪɧɟ ɤɨɧɰɟɧɬɪɚɰɢʁɟ NGAL ɢ KIM-1 ɩɪɟ ɨɩɟɪɚɰɢʁɟ, ɫɚ ʃɢɯɨɜɢɦ ɤɨɧɰɟɧɬɪɚɰɢʁɚɦɚ 1, 3, 8, 24 ɢ 72 ɫɚɬɚ ɧɚɤɨɧ ɩɚɪɰɢʁɚɥɧɟ ɧɟɮɪɟɤɬɨɦɢʁɟ ɤɨɞ 27 ɛɨɥɟɫɧɢɤɚ ɫɚ ɤɚɪɰɢɧɨɦɨɦ ɛɭɛɪɟɝɚ. Ʉɨɞ ɫɜɢɯ ɛɨɥɟɫɧɢɤɚ ʁɟ ɡɚɛɟɥɟɠɟɧ ɩɨɪɚɫɬ ɭɪɢɧɚɪɧɢɯ ɤɨɧɰɟɧɬɪɚɰɢʁɚ NGAL-ɚ ɢ KIM-1 ɧɚɤɨɧ ɨɩɟɪɚɰɢʁɟ, ɢɡɪɚɠɟɧ ɭ ɚɩɫɨɥɭɬɧɢɦ ɜɪɟɞɧɨɫɬɢɦɚ ɢ ɤɨɪɢɝɨɜɚɧ ɩɪɟɦɚ ɤɨɧɰɟɧɬɪɚɰɢʁɢ ɭɪɢɧɚɪɧɨɝ ɤɪɟɚɬɢɧɢɧɚ. ɉɨɜɟʄɚɧɚ ɤɨɧɰɟɧɬɪɚɰɢʁɚ ɭɪɢɧɚɪɧɨɝ NGAL-ɚ ɡɚɛɟɥɟɠɟɧɚ ʁɟ 1 ɫɚɬ ɧɚɤɨɧ ɢɫɯɟɦɢʁɟ ɛɭɛɪɟɝɚ ɢ ɬɪɚʁɚɥɚ ʁɟ 72 ɫɚɬɚ. ɇɚɫɭɩɪɨɬ ʃɟɦɭ, ɫɢɝɧɢɮɢɤɚɧɬɚɧ ɩɨɪɚɫɬ ɭɪɢɧɚɪɧɟ ɤɨɧɰɟɧɬɪɚɰɢʁɟ KIM-1 ɪɟɝɢɫɬɪɨɜɚɧ ʁɟ 3 ɞɨ 24 ɫɚɬɚ ɧɚɤɨɧ ɢɫɯɟɦɢʁɫɤɨɝ ɨɲɬɟʄɟʃɚ ɚɥɢ ɧɟ ɩɨɫɥɟ 24 ɢ 72 ɫɚɬɚ245. ɍ ɧɚɲɨʁ ɫɬɭɞɢʁɢ ɩɨɪɟɞɢɥɢ ɫɦɨ ɤɨɧɰɟɧɬɪɚɰɢʁɟ uKIM-1 ɩɪɟ ɨɩɟɪɚɰɢʁɟ, ɧɚ ɩɪɜɨɦ ɤɨɧɬɪɨɥɧɨɦ ɩɪɟɝɥɟɞɭ, 7.ɩɨɫɬɨɩɟɪɚɬɢɜɧɨɝ ɞɚɧɚ ɢ ɧɚ ɞɪɭɝɨɦ ɤɨɧɬɪɨɥɧɨɦ ɩɪɟɝɥɟɞɭ, 30. ɩɨɫɬɨɩɟɪɚɬɢɜɧɨɝ ɞɚɧɚ ɤɨɞ 8 ɛɨɥɟɫɧɢɤɚ ɫɚ ɉɇ ɢ 32 ɛɨɥɟɫɧɢɤɚ ɫɚ ɪɚɞɢɤɚɥɧɨɦ ɧɟɮɪɟɤɬɨɦɢʁɨɦ (Ɋɇ). ɉɨɪɟђɟʃɟɦ ɩɪɟɨɩɟɪɚɬɢɜɧɢɯ ɚɩɫɨɥɭɬɧɢɯ ɤɨɧɰɟɧɬɪɚɰɢʁɚ uKIM-1 ɢɡɦɟђɭ ɩɚɰɢʁɟɧɚɬɚ ɫɚ ɉɇ ɢ Ɋɇ, ɞɨɛɢʁɟɧɚ ʁɟ ɜɢɲɚ ɜɪɟɞɧɨɫɬ ɤɨɧɰɟɧɬɪɚɰɢʁɟ uKIM-1 ɭ ɝɪɭɩɢ ɫɚ Ɋɇ, ɚɥɢ ɛɟɡ ɫɬɚɬɢɫɬɢɱɤɟ ɡɧɚɱɚʁɧɨɫɬɢ. ɇɚ ɩɪɜɨʁ ɩɨɫɬɨɩɟɪɚɬɢɜɧɨʁ ɤɨɧɬɪɨɥɢ ɤɨɧɰɟɧɬɪɚɰɢʁɚ uKIM-1 ɭ ɝɪɭɩɢ ɫɚ ɉɇ ɪɚɫɬɟ ɭ ɨɞɧɨɫɭ ɧɚ ɩɪɟɨɩɟɪɚɬɢɜɧɟ, ɚ ɭ ɝɪɭɩɢ ɫɚ Ɋɇ ʃɟɝɨɜɚ ɤɨɧɰɟɧɬɪɚɰɢʁɚ ɩɚɞɚ ɭ ɨɞɧɨɫɭ ɧɚ ȾɂɋɄɍɋɂȳȺ 111 ɩɪɟɨɩɟɪɚɬɢɜɧɟ ɜɪɟɞɧɨɫɬɢ. ɇɚ ɩɪɜɨʁ ɩɨɫɬɨɩɟɪɚɬɢɜɧɨʁ ɤɨɧɬɪɨɥɢ ɜɪɟɞɧɨɫɬ ɚɩɫɨɥɭɬɧɟ ɤɨɧɰɟɧɬɪɚɰɢʁɟ uKIM-1 ʁɟ ɜɢɲɚ ɭ ɝɪɭɩɢ ɩɚɰɢʁɟɧɚɬɚ ɫɚ ɉɇ ɭ ɨɞɧɨɫɭ ɧɚ ɝɪɭɩɭ ɩɚɰɢʁɟɧɚɬɚ ɫɚ Ɋɇ, ɚɥɢ ɬɚ ɪɚɡɥɢɤɚ ɧɢʁɟ ɫɬɚɬɢɫɬɢɱɤɢ ɡɧɚɱɚʁɧɚ. ɇɚ ɞɪɭɝɨʁ ɩɨɫɬɨɩɟɪɚɬɢɜɧɨʁ ɤɨɧɬɪɨɥɢ ɤɨɧɰɟɧɬɪɚɰɢʁɚ uKIM-1 ɩɚɞɚ ɭ ɨɛɟ ɝɪɭɩɟ ɨɩɟɪɢɫɚɧɢɯ, ɚɥɢ ʁɟ ɢ ɞɚʂɟ ɜɢɲɚ ɭ ɝɪɭɩɢ ɫɚ ɉɇ, ɛɟɡ ɫɬɚɬɢɫɬɢɱɤɟ ɡɧɚɱɚʁɧɨɫɬɢ. ɉɨɪɟђɟʃɟɦ ɤɨɪɢɝɨɜɚɧɢɯ ɤɨɧɰɟɧɬɪɚɰɢʁɚ uKIM-1 ɞɨɛɢʁɟɧɚ ʁɟ ɢɫɬɚ ɞɢɧɚɦɢɤɚ ɩɪɨɦɟɧɟ ɤɨɧɰɟɧɬɪɚɰɢʁɟ ɨɜɨɝ ɛɢɨɦɚɪɤɟɪɚ, ɫ ɬɢɦ ɞɚ ɫɭ ɩɪɟɨɩɟɪɚɬɢɜɧɟ ɜɪɟɞɧɨɫɬɢ uKIM-1 ɭ ɝɪɭɩɢ ɩɚɰɢʁɟɧɚɬɚ ɤɨɞ ɤɨʁɢɯ ʁɟ ɭɱɢʃɟɧɚ Ɋɇ ɛɢɥɟ ɫɬɚɬɢɫɬɢɱɤɢ ɡɧɚɱɚʁɧɨ ɜɢɲɟ ɭ ɨɞɧɨɫɭ ɧɚ ʃɟɝɨɜɟ ɜɪɟɞɧɨɫɬɢ ɭ ɝɪɭɩɢ ɫɚ ɉɇ. Ɋɟɡɭɥɬɚɬɢ ɢɫɩɢɬɢɜɚʃɚ ɞɢɧɚɦɢɤɟ ɤɨɧɰɟɧɬɪɚɰɢʁɟ uKIM-1ɭ ɧɚɲɨʁ ɝɪɭɩɢ ɨɛɨɥɟɥɢɯ ɩɨɤɚɡɚɥɢ ɫɭ ɞɚ ʁɟ ɞɨ ɡɧɚɱɚʁɧɨɝ ɫɧɢɠɟʃɚ ɢ ɚɩɫɨɥɭɬɧɟ ɢ ɤɨɪɢɝɨɜɚɧɟ ɤɨɧɰɟɧɬɪɚɰɢʁɟ uKIM-1 ɞɨɲɥɨ ɫɚɦɨ ɭ ɝɪɭɩɢ ɩɚɰɢʁɟɧɚɬɚ ɥɟɱɟɧɢɯ ɪɚɞɢɤɚɥɧɨɦ ɧɟɮɪɟɤɬɨɦɢʁɨɦ ɭ ɨɛɟ ɩɨɫɬɨɩɟɪɚɬɢɜɧɟ ɤɨɧɬɪɨɥɟ, ɚɥɢ ɧɟ ɢ ɭ ɝɪɭɩɢ ɩɚɰɢʁɟɧɚɬɚ ɥɟɱɟɧɢɯ ɩɚɪɰɢʁɚɥɧɨɦ ɧɟɮɪɟɤɬɨɦɢʁɨɦ.Ɉɜɚɤɚɜ ɪɟɡɭɥɬɚɬ ʁɟ ɨɱɟɤɢɜɚɧ ɢ ɧɚɫɬɚɨ ʁɟ ɤɚɨ ɩɨɫɥɟɞɢɰɚ ɥɭɱɟʃɚ uKIM-1 ɧɚɤɨɧ ɢɫɯɟɦɢʁɫɤɨɝ ɛɭɛɪɟɠɧɨɝ ɨɲɬɟʄɟʃɚ ɢɡɚɡɜɚɧɨɝ ɩɪɢɜɪɟɦɟɧɢɦ ɡɚɬɜɚɪɚʃɟɦ ɪɟɧɚɥɧɟ ɚɪɬɟɪɢʁɟ ɬɨɤɨɦ ɩɚɪɰɢʁɚɥɧɟ ɧɟɮɪɟɤɬɨɦɢʁɟ. ɉɪɨɫɟɱɧɟ ɜɪɟɞɧɨɫɬɢ uKIM-1 ɧɢɫɭ ɫɟ ɡɧɚɱɚʁɧɨ ɪɚɡɥɢɤɨɜɚɥɟɩɪɢ ɞɪɭɝɨɦ ɤɨɧɬɪɨɥɧɨɦ ɩɪɟɝɥɟɞɭ, ɛɟɡ ɨɛɡɢɪɚ ɧɚ ɜɪɫɬɭ ɭɱɢʃɟɧɟ ɢɧɬɟɪɜɟɧɰɢʁɟ, ɲɬɨ ɩɪɟɞɫɬɚɜʂɚ ɞɨɞɚɬɧɭ, ɢɧɞɢɪɟɤɬɧɭ ɩɨɬɜɪɞɭ ɚɤɭɬɧɨɝ ɢɫɯɟɦɢʁɫɤɨɝ ɛɭɛɪɟɠɧɨɝ ɨɲɬɟʄɟʃɚ ɬɨɤɨɦ ɉɇ. ɍ ɧɚɲɨʁ ɫɬɭɞɢʁɢ ɫɦɨ ɩɨɤɚɡɚɥɢ ɞɚ ʁɟ ɢɫɯɟɦɢʁɫɤɨ ɨɲɬɟʄɟʃɟ ɛɭɛɪɟɝɚ ɧɚɫɬɚɥɨ ɬɨɤɨɦ ɉɇ ɭɬɢɰɚɥɨ ɧɚ ɩɨɜɟʄɚʃɟ ɤɨɧɰɟɧɬɪɚɰɢʁɟ uKIM-1 ɫɟɞɦɨɝ ɩɨɫɬɨɩɟɪɚɬɢɜɧɨɝ ɞɚɧɚ ɢ ɞɚ ɫɟ ɭ ɞɚʂɟɦ ɬɨɤɭ ʃɟɝɨɜɚ ɤɨɧɰɟɧɬɪɚɰɢʁɚ ɫɦɚʃɢɜɚɥɚ, ɚɥɢ ɧɟɩɨɬɩɭɧɨ, ɭɬɢɱɭʄɢ ɞɚ ɧɚ ɞɪɭɝɨʁ ɩɨɫɬɨɩɟɪɚɬɢɜɧɨʁ ɤɨɧɬɪɨɥɢ ɤɨɧɰɟɧɬɪɚɰɢʁɚ uKIM-1ɨɫɬɚɧɟ ɢ ɞɚʂɟ ɜɢɲɚ ɭ ɨɞɧɨɫɭ ɧɚ ɤɨɧɰɟɧɬɪɚɰɢʁɭ ɭ ɝɪɭɩɢ ɫɚ Ɋɇ. ɋ ɨɛɡɢɪɨɦ ɧɚ ɤɨɧɫɬɚɧɬɧɢ ɬɪɟɧɞ ɩɚɞɚ ɤɨɧɰɟɧɬɪɚɰɢʁɟ uKIM-1 ɧɚ ɨɛɟ ɩɨɫɬɨɩɟɪɚɬɢɜɧɟ ɤɨɧɬɪɨɥɟ ɭ ɝɪɭɩɢ ɩɚɰɢʁɟɧɚɬɚ ɫɚ Ɋɇ, ɤɚɨ ɢ ɱɢʃɟɧɢɰɭ ɞɚ ɫɭ ɩɪɟɨɩɟɪɚɬɢɜɧɟ ɜɪɟɞɧɨɫɬɢ ɨɜɨɝ ɛɢɨɦɚɪɤɟɪɚ ɛɢɥɟ ɫɬɚɬɢɫɬɢɱɤɢ ɡɧɚɱɚʁɧɨ ɜɢɲɟ ɭ ɨɜɨɝ ɝɪɭɩɢ ɩɚɰɢʁɟɧɚɬɚ, ɦɨɠɟɦɨ ɡɚɤʂɭɱɢɬɢ ɞɚ ɩɨɜɢɲɟɧɚ ɤɨɧɰɟɧɬɪɚɰɢʁɚ uKIM-1 ɧɚɤɨɧ ɩɚɪɰɢʁɚɥɧɟ ɧɟɮɪɟɤɬɨɦɢʁɟ ɧɢʁɟ ɬɭɦɨɪɫɤɨɝ ɩɨɪɟɤɥɚ. 5.6. Ɍɤɢɜɧɚ ɟɤɫɩɪɟɫɢʁɚ KIM-1 ɤɨɞ ɤɚɪɰɢɧɨɦɚ ɫɜɟɬɥɢɯ ʄɟɥɢʁɚ ɛɭɛɪɟɝɚ ɭ ɝɪɭɩɢ ɨɛɨɥɟɥɢɯ ɉɪɨɬɟɢɧ ɨɲɬɟʄɟʃɚ ɛɭɛɪɟɝɚ 1 (KIM-1) ɩɪɟɞɫɬɚɜʂɚ ɫɟɧɡɢɬɢɜɧɢ ɦɚɪɤɟɪ ɩɨɫɬɨʁɚʃɚ ɨɲɬɟʄɟʃɚ ɬɭɛɭɥɫɤɢɯ ɟɩɢɬɟɥɧɢɯ ʄɟɥɢʁɚ124. ɉɪɚɤɬɢɱɧɨ ʁɟ ɧɟɞɟɬɟɤɬɚɛɢɥɚɧ ɭ ɡɞɪɚɜɨɦ ɛɭɛɪɟɠɧɨɦ ɬɤɢɜɭ, ɚ ʃɟɝɨɜɚ ɬɭɛɭɥɫɤɚ ɟɤɫɩɪɟɫɢʁɚ ɩɨɜɟɡɚɧɚ ʁɟ ɫɚ ɚɤɭɬɧɢɦ ɢ ɯɪɨɧɢɱɧɢɦ ɛɭɛɪɟɠɧɢɦ ɛɨɥɟɫɬɢɦɚ ɢ ɫɪɚɡɦɟɪɧɚ ʁɟ ɫɬɟɩɟɧɭ ɬɭɛɭɥɨɢɧɬɟɪɫɬɢɰɢʁɫɤɨɝ ɨɲɬɟʄɟʃɚ ɢ ɢɧɮɥɚɦɚɰɢʁɟ141. ɍ ɫɬɚʃɢɦɚ ɢɫɯɟɦɢʁɫɤɨɝ ɢɥɢ ɬɨɤɫɢɱɧɨɝ ɛɭɛɪɟɠɧɨɝ ɨɲɬɟʄɟʃɚ, ɞɨɥɚɡɢ ɞɨ ʃɟɝɨɜɟ ɪɚɩɢɞɧɟ ɟɤɫɩɪɟɫɢʁɟ ɧɚ ɚɩɢɤɚɥɧɨʁ ɦɟɦɛɪɚɧɢ ɩɪɨɤɫɢɦɚɥɧɢɯ ɬɭɛɭɥɚ, ɩɪɢ ɱɟɦɭ ɧɢɜɨ ɭɪɢɧɚɪɧɟ ɤɨɧɰɟɧɬɪɚɰɢʁɟ KIM-1 ɤɨɪɟɥɢɪɚ ɫɚ ʃɟɝɨɜɨɦ ɟɤɫɩɪɟɫɢʁɨɦ ɭ ɛɭɛɪɟɠɧɨɦ ɬɤɢɜɭ124. ɉɨɡɧɚɬɨ ʁɟ ɞɚ ɩɨɫɬɨʁɢ ɫɬɪɨɝɚ ɩɨɜɟɡɚɧɨɫɬ ɢɡɦɟђɭ ɧɢɜɨɚ ɩɪɨɬɟɢɧɭɪɢʁɟ ɢ ɬɭɛɭɥɨɢɧɬɟɪɫɬɢɰɢʁɫɤɨɝ ɨɲɬɟʄɟʃɚ. Ɋɟɡɭɥɬɚɬɢ ɢɩɢɬɢɜɚʃɚ ɫɩɪɨɜɟɞɟɧɨɝ ɧɚ ɩɚɰɢʁɟɧɬɢɦɚ ɫɚ ɧɟɞɢʁɚɛɟɬɟɫɧɨɦ ɩɪɨɬɟɢɧɭɪɢʁɨɦ, ɩɨɤɚɡɚɥɢ ɫɭ ɞɚ ɩɨɫɬɨʁɢ ɩɨɡɢɬɢɜɧɚ ɤɨɪɟɥɚɰɢʁɚ ɢɡɦɟђɭ ɧɢɜɨɚ ɩɪɨɬɟɢɧɭɪɢʁɟ ɢ ɟɤɫɩɪɟɫɢʁɟ KIM-1 ɧɚ ɧɢɜɨɭ ɨɲɬɟʄɟɧɢɯ ɬɭɛɭɥɫɤɢɯ ɟɩɢɬɟɥɧɢɯ ʄɟɥɢʁɚ. ɂɡ ɬɨɝ ɪɚɡɥɨɝɚ ɨɞɪɟђɢɜɚʃɟ ɤɨɧɰɟɧɬɪɚɰɢʁɟ KIM-1 ȾɂɋɄɍɋɂȳȺ 112 ɭ ɭɪɢɧɭ ɩɪɟɞɫɬɚɜʂɚ ɡɧɚɱɚʁɚɧ ɧɟɢɧɜɚɡɢɜɧɢ ɩɨɤɚɡɚɬɟʂ ɟɮɢɤɚɫɧɨɫɬɢ ɪɟɧɨɩɪɨɬɟɤɬɢɜɧɟ ɬɟɪɚɩɢʁɟ246. ȿɤɫɩɪɟɫɢʁɚ KIM-1 ɭ ɬɤɢɜɭ ɛɭɛɪɟɠɧɨɝ ɚɥɨɝɪɚɮɬɚ ʁɟ ɫɟɧɡɢɬɢɜɧɢʁɢ ɦɚɪɤɟɪ ɡɚ ɞɟɬɟɤɰɢʁɭ ɪɚɧɨɝ ɬɭɛɭɥɫɤɨɝ ɨɲɬɟʄɟʃɚ ɭ ɩɨɪɟђɟʃɭ ɫɚ ɯɢɫɬɨɥɨɲɤɢɦ ɩɪɨɦɟɧɚɦɚ ɢ ɩɪɟɞɫɬɚɜʂɚ ɩɪɨɝɧɨɫɬɢɱɤɢ ɦɚɪɤɟɪ ɩɪɟɠɢɜʂɚɜɚʃɚ ɝɪɚɮɬɚ140,143. ɋɜɟɬɥɨʄɟɥɢʁɫɤɢ ɤɚɪɰɢɧɨɦ ɛɭɛɪɟɝɚɭɞɪɭɠɟɧ ʁɟ ɫɚ ɩɪɨɤɫɢɦɚɥɧɨɦ ɬɭɛɭɥɫɤɨɦ ʄɟɥɢʁɫɤɨɦ ɞɟɞɢɮɟɪɟɧɰɢʁɚɰɢʁɨɦ ɢ ɜɢɫɨɤɨɦ ɟɤɫɩɪɟɫɢʁɨɦ KIM-1, ɤɨʁɚ ɢɡɧɨɫɢ 60%247. Ɋɟɡɭɥɬɚɬɢ ɞɨ ɫɚɞɚ ɫɩɪɨɜɟɞɟɧɢɯ ɩɚɬɨɯɢɫɬɨɥɨɲɤɢɯ ɫɬɭɞɢʁɚ, ɩɨɤɚɡɚɥɢ ɫɭ ɞɚ KIM-1 ɩɪɟɞɫɬɚɜʂɚ ɪɟɥɚɬɢɜɧɨ ɫɟɧɡɢɬɢɜɚɧ ɢ ɫɩɟɰɢɮɢɱɚɧ ɦɚɪɤɟɪ ɡɚ ɞɢʁɚɝɧɨɡɭ: ɫɄȻ, ɩɄȻ, ɦɟɬɚɫɬɚɬɫɤɨɝ ɤɚɪɰɢɧɨɦɚ ɛɭɛɪɟɝɚ, ɪɚɡɥɢɤɨɜɚʃɟ ɫɄȻ ɨɞ ɯɄȻ ɢ ɨɧɤɨɰɢɬɨɦɚ, ɤɚɨ ɢ ɡɚ ɞɢʁɚɝɧɨɡɭ ɤɚɪɰɢɧɨɦɚ ɫɜɟɬɥɢɯ ʄɟɥɢʁɚ ʁɚʁɧɢɤɚ148,47. Sangoi ɢ ɫɚɪ. ɫɭ ɩɨɤɚɡɚɥɢ ɞɚ ɩɪɢɦɟɧɚ ɚɧɬɢ-KIM-1 ɚɧɬɢɬɟɥɚ ɞɨɩɪɢɧɨɫɢ ɪɚɡɥɢɤɨɜɚʃɭ ɚɞɪɟɧɚɥɧɢɯ ɤɨɪɬɢɤɚɥɧɢɯ ɧɟɨɩɥɚɡɦɢ ɨɞ ɦɟɬɚɫɬɚɡɟ ɫɄȻ ɭ ɧɚɞɛɭɛɪɟɠɧɭ ɠɥɟɡɞɭ248. ɍ ɧɚɲɨʁ ɫɬɭɞɢʁɢ ʁɟ ɪɟɡɭɥɬɚɬ ɢɦɭɧɨɯɢɫɬɨɯɟɦɢʁɫɤɨɝ ɛɨʁɟʃɚ ɫɚ KIM-1 ɚɧɬɢɬɟɥɨɦ ɨɞɪɟђɟɧ ɫɟɦɢɤɜɚɧɬɢɬɚɬɢɜɧɨ ɤɚɨ:ɧɟɝɚɬɢɜɧɚ ɪɟɚɤɰɢʁɚ=ɨɞɫɭɫɬɜɨ ɛɨʁɟʃɚ;1+=ɞɨ 10% ɢɦɭɧɨɪɟɚɤɬɢɜɧɢɯ ɬɭɦɨɪɫɤɢɯ ʄɟɥɢʁɚ; 2+ =ɨɞ 11% ɞɨ 50% ɬɭɦɨɪɫɤɢɯ ʄɟɥɢʁɚ ɫɚ ɪɟɚɤɰɢʁɨɦ; 3+ = ɜɢɲɟ ɨɞ 50% ɪɟɚɤɬɢɜɧɢɯ ɬɭɦɨɪɫɤɢɯ ʄɟɥɢʁɚ.ɂɫɬɢ ɜɢɞ ɫɤɨɪɢɪɚʃɚ KIM-1 ɩɨɡɢɬɢɜɧɢɯ ɬɭɦɨɪɫɤɢɯ ʄɟɥɢʁɚ ɤɨɪɢɫɬɢɥɢ ɫɭ Zhang ɢ ɫɚɪ. ɢ Han ɢ ɫɚɪ.ɭ ɫɜɨʁɢɦ ɫɬɭɞɢʁɚɦɚ, ɞɨɤ ʁɟ ɭ ɫɬɭɞɢʁɢ Cuadros ɢ ɫɚɪ. ɤɨɪɢɲʄɟɧ ɫɟɦɢɤɜɚɧɬɢɬɚɬɢɜɧɢ ɢɦɭɧɨ-ɯɢɫɬɨ-ɫɤɨɪ, ɤɨʁɢ ɫɟ ɞɨɛɢʁɚ ɫɚɛɢɪɚʃɟɦ ɩɪɨɰɟɧɬɚ ɢɦɭɧɨɪɟɤɬɢɜɧɢɯ ɬɭɦɨɪɫɤɢɯ ʄɟɥɢʁɚ ɢ ɢɧɬɟɧɡɢɬɟɬɚ ɛɨʁɟʃɚ249. ɍ ɧɚɲɨʁ ɫɬɭɞɢʁɢ, ɢɦɭɧɨɯɢɫɬɨɯɟɦɢʁɫɤɢɦ ɛɨʁɟʃɟɦ ɫɚ KIM-1 ɞɨɛɢʁɟɧɚ ʁɟ ɩɨɡɢɬɢɜɧɨɫɬ ɭ ɫɜɢɦ ɚɧɚɥɢɡɢɪɚɧɢɦ ɬɤɢɜɧɢɦ ɭɡɨɪɰɢɦɚ (100%). ɋɥɢɱɧɭ, ɜɢɫɨɤɭ ɢɦɭɧɨɪɟɚɤɬɢɜɧɨɫɬ ɧɚ KIM-1 ɞɨɛɢɥɢ ɫɭ ɢ ɞɪɭɝɢ ɚɭɬɨɪɢ. ɍ ɫɬɭɞɢʁɢ Zhang ɢ ɫɚɪ. ɨɞ ɭɤɭɩɧɨ ɚɧɚɥɢɡɢɪɚɧɢɯ ɬɤɢɜɚ ɫɚ ɫɄȻ, ɩɨɡɢɬɢɜɧɨɫɬ ɧɚ KIM- 1 ʁɟ ɛɢɥɚ ɩɪɢɫɭɬɧɚ ɭ 82% ɚɧɚɥɢɡɢɪɚɧɢɯ ɬɭɦɨɪɚ148. ɍ ɫɬɭɞɢʁɢ Han ɢ ɫɚɪ. ɢɦɭɧɨɪɟɤɬɢɜɧɨɫɬ ʁɟ ɛɢɥɚ ɩɪɢɫɭɬɧɚ ɤɨɞ 91% ɚɧɚɥɢɡɢɪɚɧɢɯ ɬɭɦɨɪɫɤɢɯ ɬɤɢɜɚ ɫɄȻ, ɞɨɤ ɤɨɞ ɬɭɦɨɪɚ ɤɨʁɢ ɧɢɫɭ ɩɨɤɚɡɢɜɚɥɢ ɢɦɭɧɨɪɟɤɬɢɜɧɨɫɬ, ɫɭɫɟɞɧɟ ɬɭɛɭɥɫɤɟ ʄɟɥɢʁɟ ɫɭ ɨɛɢɱɧɨ ɛɢɥɟ ɩɨɡɢɬɢɜɧɟ145. ɍ ɧɚɲɨʁ ɫɬɭɞɢʁɢ, ɤɚɨ ɢ ɭ ɫɬɭɞɢʁɢ Han ɢ ɫɚɪ., ɜɟɡɢɜɚʃɟ KIM-1ɧɢʁɟ ɭɨɱɟɧɨ ɭ ɝɥɨɦɟɪɭɥɢɦɚ, ɤɚɨ ɢ ɧɟɬɭɦɨɪɫɤɨɦ ɬɭɛɭɥɨɢɧɬɟɪɫɬɢɰɢʁɫɤɨɦ ɩɪɨɫɬɨɪɭ ɡɞɪɚɜɨɝ ɬɤɢɜɚ ɛɭɛɪɟɝɚ. ɍ ɧɚɲɨʁ ɫɬɭɞɢʁɢ, ɨɞ ɭɤɭɩɧɨ ɛɪɨʁɚ ɚɧɚɥɢɡɢɪɚɧɢɯ ɬɭɦɨɪɚ, ɤɨɞ 23 (56,10%) ɬɭɦɨɪɚ, KIM-1 ɟɤɫɩɪɟɫɢʁɚ ʁɟ ɛɢɥɚ ɩɪɢɫɭɬɧɚ ɭ ɜɢɲɟ ɨɞ 50% ɬɭɦɨɪɫɤɢɯ ʄɟɥɢʁɚ (ɨɡɧɚɱɟɧɨ ɤɚɨ 3+), ɞɨɤ ʁɟ ɤɨɞ 16 (39,02%) ɬɭɦɨɪɚ, ɢɦɭɧɨɪɟɤɬɢɜɧɨɫɬ ɛɢɥɚ ɩɪɢɫɭɬɧɚ ɭ 11-50% ɬɭɦɨɪɫɤɢɯ ʄɟɥɢʁɚ (ɨɡɧɚɱɟɧɨ ɤɚɨ 2+). ɍ ɧɚɲɨʁ ɝɪɭɩɢ ɧɢʁɟɞɚɧ ɬɭɦɨɪ ɧɢʁɟ ɩɨɤɚɡɢɜɚɨ ɟɤɫɩɪɟɫɢʁɭ KIM-1 ɦɚʃɭ ɨɞ 11%. Ⱦɨɤɚɡɚɥɢ ɫɦɨ ɞɚ ʁɟ ɩɪɟɨɩɟɪɚɬɢɜɧɚ ɚɩɫɨɥɭɬɧɚ ɢ ɤɨɪɢɝɨɜɚɧɚ ɤɨɧɰɟɧɬɪɚɰɢʁɚ KIM-1 ɭ ɭɪɢɧɭ (uKIM-1) ɛɢɥɚ ɫɪɚɡɦɟɪɧɚ ɫɬɟɩɟɧɭ KIM-1 ɬɭɦɨɪɫɤɟ ɟɤɫɩɪɟɫɢʁɟ. ɉɨɪɟђɟʃɟɦ ɚɩɫɨɥɭɬɧɢɯ ɤɨɧɰɟɧɬɪɚɰɢʁɚ uKIM-1 ɢɡɦɟђɭ ɞɜɟ ɤɚɬɟɝɨɪɢʁɟ KIM-1 ɬɭɦɨɪɫɤɟ ɟɤɫɩɪɟɫɢʁɟ (11- 50% ɢ >50%), ɧɢʁɟ ɞɨɛɢʁɟɧɚ ɫɬɚɬɢɫɬɢɱɤɢ ɡɧɚɱɚʁɧɚ ɪɚɡɥɢɤɚ, ɞɨɤ ʁɟ ɩɨɪɟђɟʃɟɦ ɤɨɪɢɝɨɜɚɧɢɯ ɤɨɧɰɟɧɬɪɚɰɢʁɚ uKIM-1 ɞɨɛɢʁɟɧɚ ɫɬɚɬɢɫɬɢɱɤɢ ɡɧɚɱɚʁɧШ ɜɢɲɚ ɤɨɧɰɟɧɬɪɚɰɢʁɚuKIM-1 ɭ ɝɪɭɩɢ ɫɚ KIM-1 ɬɭɦɨɪɫɤɨɦ ɟɤɫɩɪɟɫɢʁɨɦ ɜɟʄɨɦ ɨɞ 50% (p=0.041). KIM-1 ɬɭɦɨɪɫɤɚ ɟɤɫɩɪɟɫɢʁɚ ʁɟ ɛɢɥɚ ɫɪɚɡɦɟɪɧɚ ɞɢɦɟɧɡɢʁɢ ɬɭɦɨɪɚ. ɍ ɝɪɭɩɢ ɫɚ KIM-1 ɬɭɦɨɪɫɤɨɦ ɟɤɫɩɪɟɫɢʁɨɦ 10-50%, ɩɪɨɫɟɱɧɚ ɞɢɦɟɧɡɢʁɚ ɬɭɦɨɪɚ ʁɟ ɢɡɧɨɫɢɥɚ 4.58 (2.61) cm, ɞɨɤ ʁɟ ɨɧɚ ɛɢɥɚ ɜɟʄɚ, 5.82 (3.19) cm ɭ ɝɪɭɩɢ ɫɚ KIM-1ɟɤɫɩɪɟɫɢʁɨɦ >50%, ɚɥɢ ɬɚ ɪɚɡɥɢɤɚ ɧɢʁɟ ɛɢɥɚ ɫɬɚɬɢɫɬɢɱɤɢ ɡɧɚɱɚʁɧɚ. ɂ ɭ ȾɂɋɄɍɋɂȳȺ 113 ɫɬɭɞɢʁɢ Han ɢ ɫɚɪ. ɤɨɧɰɟɧɬɪɚɰɢʁɚ uKIM-1 ɛɢɥɚ ʁɟ ɫɪɚɡɦɟɪɧɚ ɫɬɟɩɟɧɭ ɬɭɦɨɪɫɤɟ ɟɤɫɩɪɟɫɢʁɟ KIM-1 ɢ ɜɟɥɢɱɢɧɢ ɬɭɦɨɪɚ145. ɍ ɫɬɭɞɢʁɢ Cuadros ɢ ɫɚɪ. KIM-1 ʁɟ ɛɢɨ ɟɤɫɩɪɢɦɢɪɚɧ ɭ ɬɭɦɨɪɫɤɨɦ ɬɤɢɜɭ ɫɜɢɯ ɫɄȻ. Ⱥɭɬɨɪɢ ɨɜɟ ɫɬɭɞɢʁɟ ɫɭ ɞɨɤɚɡɚɥɢ ɞɚ ʁɟ ɰɢɬɨɩɥɚɡɦɚɬɫɤɚ ɟɤɫɩɪɟɫɢʁɚ KIM-1 ɛɢɥɚ ɭ ɩɨɡɢɬɢɜɧɨʁ ɤɨɪɟɥɚɰɢʁɢ ɫɚ ɝɪɚɞɭɫɨɦ ɢ ɤɥɢɧɢɱɤɢɦ ɫɬɚɞɢʁɭɦɨɦ ɬɭɦɨɪɚ, ɞɨɤ ʁɟ ɦɟɦɛɪɚɧɫɤɚ ɟɤɫɩɪɟɫɢʁɚ ɛɢɥɚ ɭ ɨɛɪɧɭɬɨʁ ɤɨɪɟɥɚɰɢʁɢ, ɬʁ. ɛɢɥɚ ʁɟ ɦɚʃɟ ɢɡɪɚɠɟɧɚ ɤɨɞ ɦɚɥɢɝɧɢʁɢɯ ɬɭɦɨɪɚ. Ʉɨɧɰɟɩɬ ɩɨ ɤɨɦɟ ɬɭɦɨɪɢ ɜɢɫɨɤɨɝ ɯɢɫɬɨɥɨɲɤɨɝ ɝɪɚɞɭɫɚ (Fuhrman ɝɪɚɞɭɫ 3–4) ɢɦɚʁɭ ɧɢɫɤɭ ɦɟɦɛɪɚɧɫɤɭ ɟɤɫɩɪɟɫɢʁɭ, ɚɭɬɨɪɢ ɨɛʁɚɲʃɚɜɚʁɭ ɩɨɜɟʄɚɧɢɦ ɥɭɱɟʃɟɦ KIM-1 ɭ ɭɪɢɧ, ɫ ɨɛɡɢɪɨɦ ɞɚ ʁɟ ɢ ɭ ɨɜɨʁ ɫɬɭɞɢʁɢ ɞɨɤɚɡɚɧɚ ɩɨɡɢɬɢɜɧɚ ɤɨɪɟɥɚɰɢʁɚ ɢɡɦɟђɭ ɤɨɧɰɟɧɬɪɚɰɢʁɟ KIM-1 ɭ ɭɪɢɧɭ ɢ ɯɢɫɬɨɥɨɲɤɨɝ ɝɪɚɞɭɫɚ ɬɭɦɨɪɚ250. ɂ ɭ ɧɚɲɟɦ ɢɫɩɢɬɢɜɚʃɭ, ɤɨɞ ʁɟɞɢɧɨɝ ɩɚɰɢʁɟɧɬɚ ɤɨʁɢ ʁɟ ɢɦɚɨ ɫɚɪɤɨɦɚɬɨɢɞɧɭ ɮɨɪɦɭ ɄȻ, ɭɨɱɟɧɚ ʁɟ ɦɟɦɛɪɚɧɫɤɚ ɢɦɭɧɨɪɟɚɤɬɢɜɧɨɫɬ ɫɪɟɞʃɟɝ ɢɧɬɟɧɡɢɬɟɬɚ. ɇɚɭɩɪɨɬ ɬɨɦɟ, ɤɨɞ ɬɭɦɨɪɚ ɯɢɫɬɨɥɨɲɤɨɝ ɝɪɚɞɭɫɚ 3 ɭɨɱɟɧɚ ʁɟ ɢɡɪɚɠɟɧɚ ɰɢɬɨɩɥɚɡɦɚɬɫɤɚ ɪɟɚɤɬɢɜɧɨɫɬ. Ʉɚɞɚ ɫɦɨ ɩɨɪɟɞɢɥɢ KIM-1 ɬɭɦɨɪɫɤɭ ɟɤɫɩɪɟɫɢʁɭ ɫɚ ɤɚɬɟɝɨɪɢʁɚɦɚ: ɜɟɥɢɱɢɧɟ ɬɭɦɨɪɚ, ɯɢɫɬɨɥɨɲɤɨɝ ɝɪɚɞɭɫɚ, pT ɫɬɚɞɢʁɭɦɚ ɢ ɩɨɫɬɨɩɟɪɚɬɢɜɧɨɝ TNM ɫɬɚɞɢʁɭɦɚ, ɞɨɛɢʁɟɧɚ ʁɟ ɪɚɡɥɢɤɚ ɭ KIM-1ɟɤɫɩɪɟɫɢʁɢ, ɚɥɢ ɨɧɚ ɧɢʁɟ ɛɢɥɚ ɫɬɚɬɢɫɬɢɱɤɢ ɡɧɚɱɚʁɧɚ ɢɡɦɟђɭ ɪɚɡɥɢɱɢɬɢɯ ɤɚɬɟɝɨɪɢʁɚ ɧɚɜɟɞɟɧɢɯ ɯɢɫɬɨɥɨɲɤɢɯ ɤɚɪɚɤɬɟɪɢɫɬɢɤɚ ɬɭɦɨɪɚ. Ɍɭɦɨɪɢ ɞɢɦɟɧɡɢʁɚ >7 МЦ ɩɨɤɚɡɚɥɢ ɫɭ ɦɚɥɭ ɪɚɡɥɢɤɭ ɭ ɟɤɫɩɪɟɫɢʁɢ KIM-1>50% (68,33%), ɧɚɫɭɩɪɨɬ ɬɭɦɨɪɢɦɚ ɞɢɦɟɧɡɢʁɚ ≤4 МЦ (55,56%), ɚɥɢ ɭɡ ɱɢʃɟɧɢɰɭ ɞɚ ɨɞ ɭɤɭɩɧɨ 12 ɬɭɦɨɪɚ ɞɢɦɟɧɡɢʁɚ >7 МЦ, 2 ɬɭɦɨɪɫɤɚ ɭɡɨɪɤɚ (16,76%) ɧɢɫɭ ɛɢɥɚ ɞɨɫɬɭɩɧɚ ɡɚ ɢɦɭɧɨɯɢɫɬɨɯɟɦɢʁɫɤɭ ɚɧɚɥɢɡɭ ɫɚ KIM-1. Ɍɭɦɨɪɢ ɯɢɫɬɨɥɨɲɤɨɝ ɝɪɚɞɭɫɚ 3 ɩɨɤɚɡɚɥɢ ɫɭ ɟɤɫɩɪɟɫɢʁɭ KIM-1>50% ɭ 75% ɚɧɚɥɢɡɢɪɚɧɢɯ ɬɭɦɨɪɫɤɢɯ ɬɤɢɜɚ, ɞɨɤ ʁɟ ɤɨɞ ɬɭɦɨɪɚ ɝɪɚɞɭɫɚ 2 ɨɜɚʁ ɧɢɜɨ KIM-1 ɟɤɫɩɪɟɫɢʁɟ ɛɢɨ ɩɪɢɫɭɬɚɧ ɤɨɞ 50% ɬɭɦɨɪɚ. Ʉɨɞ ɬɭɦɨɪɚ pT3a ɫɬɚɞɢʁɭɦɚ ɟɤɫɩɪɟɫɢʁɭ KIM-1>50% ɩɨɤɚɡɢɜɚɥɨ ʁɟ 64% ɬɭɦɨɪɚ, ɧɚɫɭɩɪɨɬ 54% ɤɨɞ ɬɭɦɨɪɚ ɫɬɚɞɢʁɭɦɚ pT1a. ɉɨɪɟђɟʃɟɦ ɩɨɫɬɨɩɟɪɚɬɢɜɧɨɝ TNM ɫɬɚɞɢʁɭɦɚ, ɩɨɤɚɡɚɧɨ ʁɟ ɞɚ ɫɭ ɬɭɦɨɪɢ TNM III ɫɬɚɞɢʁɭɦɚ ɢɦɚɥɢ ɟɤɫɩɪɟɫɢʁɭ KIM-1>50% ɭ 69,23% ɬɭɦɨɪɚ, ɧɚɫɭɩɪɨɬ 47,83% ɤɨɞ ɬɭɦɨɪɚ TNM I ɩɨɫɬɨɩɟɪɚɬɢɜɧɨɝ ɫɬɚɞɢʁɭɦɚ. ɋɬɚɬɢɫɬɢɱɤɢ ɡɧɚɱɚʁɧɚ ɪɚɡɥɢɤɚ ɭ KIM-1 ɬɭɦɨɪɫɤɨʁ ɟɤɫɩɪɟɫɢʁɢ ɞɨɛɢʁɟɧɚ ʁɟ ɫɚɦɨ ɢɡɦɟђɭ ɪɚɡɥɢɱɢɬɢɯ ɤɚɬɟɝɨɪɢʁɚ Ʌȼɂ (p=0.041). Ʌɢɦɮɧɨ-ɜɚɫɤɭɥɚɪɧɚ ɢɧɜɚɡɢʁɚ (Ʌȼɂ) ɫɟ ɞɟɮɢɧɢɲɟ ɤɚɨ ɩɪɢɫɭɫɬɜɨ ɦɚɥɢɝɧɢɯ ʄɟɥɢʁɚ ɭ ɡɢɞɭ ɤɪɜɧɨɝ ɫɭɞɚ ɢɥɢ ɧɟɨɩɥɚɫɬɢɱɤɢɯ ɟɦɛɨɥɭɫɚ ɭ ɥɭɦɟɧɭ ɢɧɬɪɚɬɭɦɨɪɫɤɨɝ ɤɪɜɧɨɝ ɫɭɞɚ. Ⱦɨɤɚɡɚɧɚ ʁɟ ɩɨɜɟɡɚɧɨɫɬ Ʌȼɂ ɫɚ ɜɢɲɢɦ ɫɬɚɞɢʁɭɦɨɦ ɢ ɝɪɚɞɭɫɨɦ ɬɭɦɨɪɚ, ɤɚɨ ɢ ɜɟʄɢɦ ɪɢɡɢɤɨɦ ɨɞ ɦɟɬɚɫɬɚɡɚ ɭ ɥɢɦɮɧɟ ɱɜɨɪɨɜɟ, ɤɚɨ ɢ ɭɞɚʂɟɧɢɯ ɦɟɬɚɫɬɚɡɚ233, 234. Ʉɨɞ ɧɚɲɢɯ ɩɚɰɢʁɟɧɚɬɚ ɫɚ ɩɪɢɫɭɬɧɨɦ ɢ ɥɢɦɮɧɨɦ ɢ ɜɚɫɤɭɥɚɪɧɨɦ ɬɭɦɨɪɫɤɨɦ ɢɧɜɚɡɢʁɨɦ, ɭɤɭɩɧɨ 21, 14 ɩɚɰɢʁɟɧɚɬɚ ʁɟ ɢɦɚɥɨ pT3a ɫɬɚɞɢʁɭɦ, ɯɢɫɬɨɥɨɲɤɢ ɝɪɚɞɭɫ 3 ɢɦɚɥɨ ʁɟ 9 ɩɚɰɢʁɟɧɚɬɚ, ʁɟɞɚɧ ɩɚɰɢʁɟɧɬ ɯɢɫɬɨɥɨɲɤɢ ɝɪɚɞɭɫ 4 ɢ ʁɟɞɚɧ ɩɚɰɢʁɟɧɬ ʁɟ ɢɦɚɨ ɦɟɬɚɫɬɚɬɫɤɭ ɛɨɥɟɫɬ. ɇɢ ʁɟɞɚɧ ɩɚɰɢʁɟɧɬ ɧɢʁɟ ɢɦɚɨ ɦɟɬɚɫɬɚɡɭ ɭ ɥɢɦɮɧɢɦ ɱɜɨɪɨɜɢɦɚ. Ɍɭɦɨɪɢ ɤɨʁɢ ɫɭ ɩɨɤɚɡɢɜɚɥɢ ɢ ɥɢɦɮɧɭ ɢ ɜɚɫɤɭɥɚɪɧɭ ɢɧɜɚɡɢʁɭ ɭ ɡɧɚɱɚʁɧɨ ɜɟʄɟɦ ɩɪɨɰɟɧɬɭ (71,43%) ɢɦɚɥɢ ɫɭ KIM-1 ɢɦɭɧɨɪɟɚɤɬɢɜɧɨɫɬ ɜɟʄɭ ɨɞ 50% ɭ ɨɞɧɨɫɭ ɧɚ ɬɭɦɨɪɟ ɛɟɡ ɥɢɦɮɧɟ ɢ ɜɚɫɤɭɥɚɪɧɟ ɢɧɜɚɡɢʁɟ (28,57%). Ɍɚ ɪɚɡɥɢɤɚ ʁɟ ɩɨɫɬɨʁɚɥɚ ɢ ɭ ɨɞɧɨɫɭ ɧɚ ɬɭɦɨɪɟ ɤɨʁɢ ɫɭ ɩɨɤɚɡɢɜɚɥɢ ɥɢɦɮɧɭ ɢɥɢ ɜɚɫɤɭɥɚɪɧɭ ɢɧɜɚɡɢʁɭ (46,15%) ɚɥɢ ɛɟɡ ɫɬɚɬɢɫɬɢɱɤɟ ɡɧɚɱɚʁɧɨɫɬɢ. ɍ ɫɬɭɞɢʁɚɦɚ ȾɂɋɄɍɋɂȳȺ 114 ɞɪɭɝɢɯ ɚɭɬɨɪɚ ɧɢʁɟ ɢɫɩɢɬɢɜɚɧɚ ɩɨɜɟɡɚɧɨɫɬ ɢɡɦɟђɭ ɟɤɫɩɪɟɫɢʁɟ KIM-1 ɢ ɥɢɦɮɧɨ-ɜɚɫɤɭɥɚɪɧɟ ɢɧɜɚɡɢʁɟ. ɋ ɨɛɡɢɪɨɦ ɧɚ ɩɨɞɚɬɚɤ ɞɚ ɩɄȻ ɧɚɫɬɚʁɟ ɤɚɨ ɢ ɫɄȻ ɞɟɞɢɮɟɪɟɧɰɢʁɚɰɢʁɨɦ ʄɟɥɢʁɚ ɩɪɨɤɫɢɦɚɥɧɨɝ ɬɭɛɭɥɚ, ɞɨɤɚɡɚɧɚ ʁɟ KIM-1 ɩɨɡɢɬɢɜɧɨɫɬ ɢ ɭ ɨɜɨɦ ɩɨɞɬɢɩɭ ɄȻ145,148. ɍ ɧɚɲɨʁ ɫɬɭɞɢʁɢ ʁɟ ɤɨɞ ʁɟɞɧɨɝ ɩɚɰɢʁɟɧɬɚ ɩɚɬɨɯɢɫɬɨɥɨɲɤɨɦ ɚɧɚɥɢɡɨɦ, ɩɨɪɟɞ ɫɄȻ ɞɢʁɚɝɧɨɫɬɢɤɨɜɚɧ ʁɟ ɩɚɩɢɥɚɪɧɢ ɩɨɞɬɢɩ 1 ɄȻ ɤɨʁɢ ʁɟ ɩɨɤɚɡɚɨ ɢɡɪɚɡɢɬɨ ɩɨɡɢɬɢɜɧɭ ɰɢɬɨɩɥɚɡɦɚɬɫɤɭ ɢɦɭɧɨɪɟɚɤɬɢɜɧɨɫɬ ɧɚ KIM-1. Ɋɟɡɭɥɬɚɬɢ ɧɚɲɟ ɫɬɭɞɢʁɟ ɫɭ ɩɨɤɚɡɚɥɢ ɞɚ KIM-1 ɩɪɟɞɫɬɚɜʂɚ ɜɢɫɨɤɨ ɫɟɧɡɢɬɢɜɚɧ ɬɤɢɜɧɢ ɦɚɪɤɟɪ ɡɚ ɩɨɬɜɪɞɭ ɞɢʁɚɝɧɨɡɟ ɫɄȻ, ɤɨʁɢ ʁɟ ɫɚ ɜɢɫɨɤɢɦ ɫɬɟɩɟɧɨɦ ɢɦɭɧɨɪɟɚɤɬɢɜɧɨɫɬɢ ɞɨɤɚɡɚɧ ɭ ɬɤɢɜɧɢɦ ɭɡɨɪɰɢɦɚ ɫɜɢɯ ɩɚɰɢʁɟɧɚɬɚ ɫɚ ɫɄȻ. 5.7. ɉɪɟɨɩɟɪɚɬɢɜɧɟ ɜɪɟɞɧɨɫɬɢ AQP-1 ɭ ɭɪɢɧɭ ɢ ɩɚɬɨɯɢɫɬɨɥɨɲɤɟ ɤɚɪɚɤɬɟɪɢɫɬɢɤɟ ɬɭɦɨɪɚ ɝɪɭɩɢ ɨɛɨɥɟɥɢɯ ɨɞ ɤɚɪɰɢɧɨɦɚ ɫɜɟɬɥɢɯ ʄɟɥɢʁɚ ɛɭɛɪɟɝɚ Ⱥɤɜɚɩɨɪɢɧ1 (AQP-1) ɩɪɟɞɫɬɚɜʂɚ ɩɪɜɢ ɢɧɞɟɧɬɢɮɢɤɨɜɚɧɢ ɦɟɦɛɪɚɧɫɤɢ ɬɪɚɧɫɩɨɪɬɧɢ ɩɪɨɬɟɢɧ ɡɚ ɜɨɞɭ. AQP-1 ʁɟ ɥɨɤɚɥɢɡɨɜɚɧ ɧɚ ɚɩɢɤɚɥɧɨʁ ɢ ɛɚɡɨɥɚɬɟɪɚɥɧɨʁ ɦɟɦɛɪɚɧɢ ɩɪɨɤɫɢɦɚɥɧɨɝ ɬɭɛɭɥɚ ɢ ɬɚɧɤɨɦ ɧɢɫɯɨɞɧɨɦ ɤɪɚɤɭ ɏɟɧɥɟɨɜɟ ɩɟɬʂɟ ɢ ɨɞɝɨɜɨɪɚɧ ʁɟ ɡɚ ɪɟɚɩɫɨɪɩɰɢʁɭ 75% ɜɨɞɟ ɢɡ ɝɥɨɦɟɪɭɥɚɪɧɨɝ ɮɢɥɬɪɚɬɚ, ɱɢɦɟ ɩɪɟɞɫɬɚɜʂɚ ɝɥɚɜɧɢ ɱɢɧɢɥɚɰ ɭ ɦɟɯɚɧɢɡɦɭ ɤɨɧɰɟɧɬɪɚɰɢʁɟ ɭɪɢɧɚ. ȿɤɫɩɪɟɫɢʁɚ AQP-1 ɧɚ ɝɥɨɦɟɪɭɥɚɪɧɢɦ ɟɧɞɨɬɟɥɧɢɦ ʄɟɥɢʁɚɦɚ ʁɟ ɡɧɚɱɚʁɧɨ ɩɨɜɟʄɚɧɚ ɭ ɦɧɨɝɢɦ ɝɥɨɦɟɪɭɥɫɤɢɦ ɛɨɥɟɫɬɢɦɚ ɤɚɨ ɲɬɨ ɫɭ: ɛɨɥɟɫɬ ɦɢɧɢɦɚɥɧɢɯ ɩɪɨɦɟɧɚ, ɯɪɨɧɢɱɧɢ ɦɟɡɚɧɝɢɨɩɪɨɥɢɮɟɪɚɬɢɜɧɢ ɝɥɨɦɟɪɭɥɨɧɟɮɪɢɬɢɫ, crescentic ɝɥɨɦɟɪɭɥɨɧɟɮɪɢɬɢɫ, ɥɭɩɭɫ ɧɟɮɪɢɬɢɫ, ɬɭɛɭɥɨɢɧɬɟɪɫɬɢɰɢʁɫɤɢ ɧɟɮɪɢɬɢɫ, ɧɟɮɪɨɫɤɥɟɪɨɡɚ154. ɇɟɞɚɜɧɨ ɨɬɤɪɢʄɟ ɨ ɭɱɟɲʄɭ AQP ɭ ɩɪɨɰɟɫɭ ɬɭɦɨɪɫɤɟ ʄɟɥɢʁɫɤɟ ɩɪɨɥɢɮɟɪɚɰɢʁɟ ɢ ɦɢɝɪɚɰɢʁɟ, ɭɤɚɡɭʁɟ ɞɚ ɚɤɜɚɩɨɪɢɧɢ ɢɦɚʁɭ ɡɧɚɱɚʁɧɭ ɭɥɨɝɭ ɭ ɛɢɨɥɨɝɢʁɢ ɬɭɦɨɪɚ. Ɍɭɦɨɪɫɤɟ ʄɟɥɢʁɟ ɟɤɫɩɪɢɦɢɪɚʁɭ ɚɤɜɚɩɨɪɢɧɟ, ɚ ɫɬɟɩɟɧ ʃɢɯɨɜɟ ɟɤɩɪɟɫɢʁɟ ɤɨɪɟɥɢɪɚ ɫɚ ɯɢɫɬɨɥɨɲɤɢɦ ɫɬɟɩɟɧɨɦ ɬɭɦɨɪɚ. ɇɟɞɚɜɧɨ ʁɟ ɨɬɤɪɢɜɟɧɨ ɞɚ ɫɟ ɚɤɜɚɩɨɪɢɧɢ ɦɨɝɭ ɫɟɤɪɟɬɨɜɚɬɢ ɭ ɭɪɢɧ, ɤɚɨ ɲɬɨ ʁɟ ɫɥɭɱɚʁ ɫɚ AQP-1 ɭ ɫɥɭɱɚʁɭ ɨɲɬɟʄɟʃɚ ɩɪɨɤɫɢɦɚɥɧɨɝ ɬɭɛɭɥɚ158. ɍ ɧɚɲɨʁ ɫɬɭɞɢʁɢ ɫɦɨ ɩɨɪɟђɟʃɟɦ ɚɩɫɨɥɭɬɧɢɯ ɢ ɤɨɪɢɝɨɜɚɧɢɯ ɤɨɧɰɟɧɬɪɚɰɢʁɚ AQP-1 ɭ ɭɪɢɧɭ (uAQP-1) ɨɛɨɥɟɥɢɯ ɩɪɟ ɨɩɟɪɚɰɢʁɟ, ɧɚ ɩɪɜɨʁ ɢ ɞɪɭɝɨʁ ɩɨɫɬɨɩɟɪɚɬɢɜɧɨʁ ɤɨɧɬɪɨɥɢ, ɞɨɛɢɥɢ ɧɚʁɧɢɠɭ ɜɪɟɞɧɨɫɬɢ ɨɜɨɝ ɭɪɢɧɚɪɧɨɝ ɛɢɨɦɚɪɤɟɪɚ ɩɪɟɨɩɟɪɚɬɢɜɧɨ. ɇɚɤɨɧ ɨɩɟɪɚɰɢʁɟ, ɤɨɧɰɟɧɬɪɚɰɢʁɚ uAQP-1 ɪɚɫɬɟ ɢ ɞɨɫɬɢɠɟ ɧɚʁɜɢɲɭ ɤɨɧɰɟɧɬɪɚɰɢʁɭ ɧɚ ɞɪɭɝɨʁ ɩɨɫɬɨɩɟɪɚɬɢɜɧɨʁ ɤɨɧɬɪɨɥɢ. ɇɢʁɟ ɞɨɛɢʁɟɧɚ ɫɬɚɬɢɫɬɢɱɤɢ ɡɧɚɱɚʁɧɚ ɪɚɡɥɢɤɚ ɭ ɤɨɧɰɟɧɬɪɚɰɢʁɢ uAQP-1 ɩɪɟ ɢ ɩɨɫɥɟ ɨɩɟɪɚɰɢʁɟ, ɤɚɨ ɢ ɢɡɦɟђɭ ɩɪɜɟ ɢ ɞɪɭɝɟ ɩɨɫɬɨɩɟɪɚɬɢɜɧɟ ɤɨɧɬɪɨɥɟ. ɉɪɟɨɩɟɪɚɬɢɜɧɚ ɜɪɟɞɧɨɫɬ ɤɨɪɢɝɨɜɚɧɟ ɤɨɧɰɟɧɬɪɚɰɢʁɟ uAQP1 ɭ ɧɚɲɨʁ ɝɪɭɩɢ ɨɛɨɥɟɥɢɯ ɛɢɥɚ ʁɟ ɫɬɚɬɢɫɬɢɱɤɢ ɡɧɚɱɚʁɧɨ ɧɢɠɚ ɭ ɨɞɧɨɫɭ ɧɚ ʃɟɧɭ ɜɪɟɞɧɨɫɬ ɭ ɝɪɭɩɢ ɡɞɪɚɜɢɯ (p=0.031). ɇɚɤɨɧ ɨɩɟɪɚɰɢʁɟ ɤɨɧɰɟɧɬɪɚɰɢʁɚ uAQP1 ɭ ɝɪɭɩɢ ɨɛɨɥɟɥɢɯ ɪɚɫɬɟ ɢ ɞɨɫɬɢɠɟ ɧɚʁɜɢɲɭ ɜɪɟɞɧɨɫɬ ɧɚ ɞɪɭɝɨʁ ɩɨɫɬɨɩɟɪɚɬɢɜɧɨʁ ɤɨɧɬɪɨɥɢ. Ʉɚɞɚ ɫɦɨ ɭɩɨɪɟɞɢɥɢ ɩɪɟɨɩɟɪɚɬɢɜɧɭ ɜɪɟɞɧɨɫɬ ɤɨɪɢɝɨɜɚɧɟ ɤɨɧɰɟɧɬɪɚɰɢʁɟ uAQP-1ɩɪɟɦɚ ɤɚɬɟɝɨɪɢʁɢ ɜɟɥɢɱɢɧɟ ɬɭɦɨɪɚ (≤4 cm, 4.1-7 cm ɢ >7cm) ɭ ɝɪɭɩɢ ɨɛɨɥɟɥɢɯ, ɨɧɚ ʁɟ ɛɢɥɚ ɧɢɠɚ ɭ ɫɜɢɦ ɤɚɬɟɝɨɪɢʁɚɦɚ ɜɟɥɢɱɢɧɟ ɭ ɨɞɧɨɫɭ ɧɚ ɤɨɧɰɟɧɬɪɚɰɢʁɭ uAQP-1 ɭ ɝɪɭɩɢ ɡɞɪɚɜɢɯ, ɛɟɡ ɫɬɚɬɢɫɬɢɱɤɟ ɡɧɚɱɚʁɧɨɫɬɢ, ɦɚɞɚ ɫɟ ɩɪɢɛɥɢɠɚɜɚ (p=0.058). ɋɬɚɬɢɫɬɢɱɤɢ ɡɧɚɱɚʁɧɚ ɪɚɡɥɢɤɚ (p*=0.015) ɞɨɛɢʁɟɧɚ ʁɟ ɫɚɦɨ ɢɡɦɟђɭ ɤɨɪɢɝɨɜɚɧɟ ȾɂɋɄɍɋɂȳȺ 115 ɤɨɧɰɟɧɬɪɚɰɢʁɟ uAQP-1 ɭ ɝɪɭɩɢ ɩɚɰɢʁɟɧɚɬɚ ɫɚ ɬɭɦɨɪɢɦɚ ɞɢɦɟɧɡɢʁɚ 4.1-7 cm ɢ uAQP-1 ɭ ɝɪɭɩɢ ɡɞɪɚɜɢɯ. Ʉɚɞɚ ɫɦɨ ɩɨɪɟɞɢɥɢ ɚɩɫɨɥɭɬɧɭ ɢ ɤɨɪɢɝɨɜɚɧɭ ɤɨɧɰɟɧɬɪɚɰɢʁɭ uAQP-1 ɭ ɝɪɭɩɢ ɨɛɨɥɟɥɢɯ ɫɚ ɩɚɬɨɯɢɫɬɨɥɨɲɤɢɦ ɤɚɪɚɤɬɟɪɢɫɬɢɤɚɦɚ ɬɭɦɨɪɚ ɢ ɬɨ: ɜɟɥɢɱɢɧɨɦ, ɧɭɤɥɟɪɧɢɦ ɝɪɚɞɭɫɨɦ, pT ɫɬɚɞɢʁɭɦɨɦ, ɥɢɦɮɧɨ-ɜɚɫɤɭɥɚɪɧɨɦ ɢɧɜɚɡɢʁɨɦ ɢ ɩɨɫɬɨɩɟɪɚɬɢɜɧɢɦ TNM ɫɬɚɞɢʁɭɦɨɦ, ɧɢʁɟ ɞɨɛɢʁɟɧɚ ɫɬɚɬɢɫɬɢɱɤɢ ɡɧɚɱɚʁɧɚ ɩɨɜɟɡɚɧɨɫɬ ɢɡɦɟђɭ uAQP-1 ɢ ɧɚɜɟɞɟɧɢɯ ɯɢɫɬɨɥɨɲɤɢɯ ɤɚɪɚɤɬɟɪɢɫɬɢɤɚ ɬɭɦɨɪɚ. Ɂɚ ɪɚɡɥɢɤɭ ɨɞ ɧɚɲɢɯ ɪɟɡɭɥɬɚɬɚ, ɞɪɭɝɢ ɚɭɬɨɪɢ ɫɭ ɭ ɫɜɨʁɢɦ ɫɬɭɞɢʁɚɦɚ ɞɨɛɢɥɢ ɫɭɩɪɨɬɧɟ ɧɚɥɚɡɟ. Morrissey ɢ ɫɚɪ. ɫɭ ɭ ɩɪɜɨʁ ɫɬɭɞɢʁɢ ɤɨʁɚ ʁɟ ɢɫɩɢɬɢɜɚɥɢ ɨɜɚʁ ɭɪɢɧɚɪɧɢ ɛɢɨɦɚɪɤɟɪ ɧɚɲɥɢ ɫɬɚɬɢɫɬɢɱɤɢ ɡɧɚɱɚʁɧɨ ɜɢɲɭ ɩɪɟɨɩɟɪɚɬɢɜɧɭ ɤɨɧɰɟɧɬɪɚɰɢʁɭ uAQP-1 ɭ ɝɪɭɩɢ ɩɚɰɢʁɟɧɚɬɚ ɫɚ ɫɄȻ ɭ ɩɨɪɟђɟʃɭ ɫɚ ɤɨɧɬɪɨɥɧɨɦ ɝɪɭɩɨɦ121. Ɍɚɤɨђɟ, ɩɨɤɚɡɚɧɚ ʁɟ ɞɢɪɟɤɬɧɚ ɤɨɪɟɥɚɰɢʁɚ ɢɡɦɟђɭ ɤɨɧɰɟɧɬɪɚɰɢʁɟ uAQP-1ɢ ɜɟɥɢɱɢɧɟ ɬɭɦɨɪɚ. ɂɫɬɢ ɚɭɬɨɪ ʁɟ ɬɪɢ ɝɨɞɢɧɟ ɤɚɫɧɢʁɟ ɨɛʁɚɜɢɨ ɪɟɡɭɥɚɬɚɬɟ ɫɬɭɞɢʁɟ ɭ ɤɨʁɢɦɚ ʁɟ ɢɫɩɢɬɢɜɚɨ ɫɟɧɡɢɬɢɜɧɨɫɬ ɢ ɫɩɟɰɢɮɢɱɧɨɫɬ AQP-1 ɢ ɚɞɢɩɨɮɢɥɢɧɚ (ADFP) ɡɚ ɞɢʁɚɝɧɨɡɭ ɤɚɪɰɢɧɨɦɚ ɛɭɛɪɟɝɚ. Ɋɟɡɭɥɬɚɬɢ ɫɬɭɞɢʁɟ ɫɭ ɩɨɤɚɡɚɥɢ ɞɚ ɨɞɪɟђɢɜɚʃɟ ɤɨɧɰɟɧɬɪɚɰɢʁɟ uAQP-1 ɦɨɠɟ ɭɤɚɡɚɬɢ ɧɚ ɩɨɫɬɨʁɚʃɟ ɫɄȻ ɢɥɢ ɩɄȻ, ɛɟɡ ɭɬɢɰɚʁɚ ɞɪɭɝɢɯ ɧɚʁɱɟɲʄɢɯ ɛɨɥɟɫɬɢ ɛɭɛɪɟɝɚ ɧɚ ʃɟɝɨɜɭ ɤɨɧɰɟɧɬɪɚɰɢʁɭ159. Morrissey ɢ ɫɚɪ. ɫɭ ɤɪɚʁɟɦ 2013. ɝɨɞɢɧɟ ɨɛʁɚɜɢɥɢ ɪɟɡɭɥɬɚɬɟ ɫɜɨʁɟ ɩɨɫɥɟɞʃɟ ɫɬɭɞɢʁɟ, ɭ ɤɨʁɨʁ ʁɟ ɩɚɰɢʁɟɧɬɢɦɚ ɫɚ ɯɢɫɬɨɥɨɲɤɢ ɞɢʁɚɝɧɨɫɬɢɤɨɜɚɧɢɦ ɫɄȻ ɢɥɢ ɩɄȻ, ɩɪɟɨɩɟɪɚɬɢɜɧɨ ɢ ɩɨɫɬɨɩɟɪɚɬɢɜɧɨ ɨɞɪɟђɢɜɚɧɚ ɤɨɧɰɟɧɬɪɚɰɢʁɚ AQP-1 ɢ ɩɟɪɢɥɢɩɢɧɚ (PLIN2). ɋɬɭɞɢʁɚ ʁɟ ɩɨɤɚɡɚɥɚ ɞɚ ɫɟɧɡɢɬɢɜɧɨɫɬ ɢ ɫɩɟɰɢɮɢɱɧɨɫɬ AQP-1 ɡɚ ɞɢʁɚɝɧɨɡɭ ɫɄȻ ɢ ɩɄȻ ɢɡɧɨɫɢ 100%, ɤɚɨ ɢ ɞɚ ɩɪɟɨɩɟɪɚɬɢɜɧɚ ɤɨɧɰɟɧɬɪɚɰɢʁɚ ɨɜɨɝ ɛɢɨɦɚɪɤɟɪɚ ɤɨɪɟɥɢɪɚ ɫɚ ɜɟɥɢɱɢɧɨɦ ɢ ɫɬɚɞɢʁɭɦɨɦ ɬɭɦɨɪɚ, ɚɥɢ ɧɟ ɢ ɫɚ ɝɪɚɞɭɫɨɦ ɬɭɦɨɪɚ160. ɍ ɧɚɜɟɞɟɧɢɦ ɫɬɭɞɢʁɚɦɚ Morrissey ɢ ɫɚɪ. ɡɚ ɨɞɪɟђɢɜɚʃɟ ɩɪɢɫɭɫɬɜɚ AQP-1 ɭ ɭɪɢɧɭ ɤɨɪɢɲʄɟɧ ʁɟ ɫɟɧɡɢɬɢɜɧɢ ɢ ɫɩɟɰɢɮɢɱɧɢ Western blot ɬɟɫɬ. Ɂɚɤʂɭɱɚɤ ɚɭɬɨɪɚ ɞɚ ʁɟ ɬɟɫɬ ɝɥɨɦɚɡɚɧ, ɬɟ ʁɟ ɧɟɨɩɯɨɞɧɨ ɪɚɡɜɢɬɢ ɫɟɧɡɢɬɢɜɚɧ ɢ ɫɩɟɰɢɮɢɱɚɧ ELISA ɬɟɫɬ ɡɚ ɨɞɪɟђɢɜɚʃɟ uAQP-1. ɋɥɢɱɧɨ ɧɚɜɟɞɟɧɢɦ ɚɭɬɨɪɢɦɚ, Sreedharan ɢ ɫɚɪ. ɫɭ Western blot ɬɟɯɧɢɤɨɦ ɨɞɪɟђɢɜɚʃɚ uAQP-1, ɧɚɲɥɢ ɫɬɪɨɝɭ ɩɨɡɢɬɢɜɧɭ ɤɨɪɟɥɚɰɢʁɭ ɢɡɦɟђɭ ɩɪɟɨɩɟɪɚɬɢɜɧɟ ɤɨɧɰɟɧɬɪɚɰɢʁɟ uAQP-1 ɢ ɯɢɫɬɨɥɨɲɤɟ ɞɢʁɚɝɧɨɡɟɫɄȻ161. ɋ ɨɛɡɢɪɨɦ ɧɚ ɦɚɥɢ ɛɪɨʁ ɚɧɚɥɢɡɢɪɚɧɢɯ ɩɚɰɢʁɟɧɚɬɚ, ɭɤɭɩɧɨ11,ɧɢʁɟ ɜɪɲɟɧɚ ɤɨɪɟɥɚɰɢʁɚ ɢɡɦɟђɭ ɤɨɧɰɟɧɬɪɚɰɢʁɟ uAQP-1 ɢ ɩɚɬɨɯɢɫɬɨɥɨɲɤɢɯ ɤɚɪɚɤɬɟɪɢɫɬɢɤɚ ɬɭɦɨɪɚ. Ɂɚ ɪɚɡɥɢɤɭ ɨɞ ɧɚɜɟɞɟɧɢɯ ɫɬɭɞɢʁɚ ɭ ɤɨʁɢɦɚ ʁɟ ɤɨɧɰɟɧɬɪɚɰɢʁɚ uAQP-1 ɨɞɪɟђɢɜɚɧɚ Western blot ɬɟɯɧɢɤɨɦ, ɭ ɧɚɲɨʁ ɫɬɭɞɢʁɢ ɤɨɪɢɲʄɟɧ ʁɟ ɤɨɦɟɪɰɢʁɚɥɧɢ ELISA ɬɟɫɬ ɡɚ ɤɜɚɧɬɢɬɚɬɢɜɧɨ ɨɞɪɟђɢɜɚʃɟ ɨɜɨɝ ɭɪɢɧɚɪɧɨɝ ɛɢɨɦɚɪɤɟɪɚ. ɉɪɟɬɯɨɞɧɨ ɫɭ ɭɡɨɪɰɢ ɭɪɢɧɚ ɚɞɟɤɜɚɬɧɨ ɨɛɪɚђɟɧɢ ɢ ɡɚɦɪɡɧɭɬɢ ɧɚ –80̊ C ɞɨ ɬɪɟɧɭɬɤɚ ɚɧɚɥɢɡɟ. ɉɪɟɦɚ ɧɚɦɚ ɞɨɫɬɭɩɧɢɦ ɩɨɞɚɰɢɦɚ, ɨɜɨ ʁɟ ɩɪɜɢ ɩɭɬ ɞɚ ʁɟ ɤɨɦɟɪɰɢʁɚɥɧɢ ELISA ɬɟɫɬ ɤɨɪɢɲʄɟɧ ɡɚ ɨɞɪɟђɢɜɚʃɟ ɤɨɧɰɟɧɬɪɚɰɢʁɟ AQP-1 ɭ ɭɪɢɧɭ. ɇɚɥɚɡ ɫɧɢɠɟɧɟ ɤɨɧɰɟɧɬɪɚɰɢʁɟ uAQP-1ɭ ɧɚɲɨʁ ɫɬɭɞɢʁɢ ɛɢ ɫɟ ɞɟɥɢɦɢɱɧɨ ɦɨɝɚɨ ɨɛʁɚɫɧɢɬɢ ɪɟɡɭɥɬɚɬɢɦɚ ɢɦɭɧɨɯɢɫɬɨɯɟɦɢʁɫɤɢɯ ɫɬɭɞɢʁɚ ɨ ɟɤɫɩɪɟɫɢʁɢ AQP-1 ɭ ɬɤɢɜɭ ɫɄȻ. Ticozzi- Valerio ɢ ɫɚɪ. ɫɭ ɞɨɤɚɡɚɥɢ ɫɦɚʃɟʃɟ ɟɤɫɩɪɟɫɢʁɟ AQP-1 ɭ ɬɤɢɜɭ ɫɄȻ ɨɞ ɭɦɟɪɟɧɟ ɞɨ ɫɤɨɪɨ ɤɨɦɩɥɟɬɧɟ, ɡɚɜɢɫɧɨ ɨɞ ɝɪɚɞɭɫɚ ɬɭɦɨɪɚ251. Ɍɭɦɨɪɢ ɜɢɫɨɤɨɝ ɯɢɫɬɨɥɨɲɤɨɝ ɝɪɚɞɭɫɚ ɩɨɤɚɡɢɜɚɥɢ ɫɭ ɜɟʄɭ ɪɟɞɭɤɰɢʁɭ ɬɤɢɜɧɟ ɟɤɫɩɪɟɫɢʁɟ AQP-1 ɭ ɩɨɪɟђɟʃɭ ɫɚ ɡɞɪɚɜɢɦ ɬɤɢɜɨɦ ɛɭɛɪɟɝɚ.Mazal ɢ ɫɚɪ. ɫɭ ɭ ɫɜɨʁɨʁ ɫɬɭɞɢʁɢ ɞɨɤɚɡɚɥɢ ɫɢɝɧɢɮɢɤɚɧɬɧɨ ɫɦɚʃɟʃɟ ɢɥɢ ɝɭɛɢɬɚɤ ɟɤɫɩɪɟɫɢʁɟ AQP-1 ɤɨɞ ɫɄȻ ɜɢɫɨɤɨɝ ɧɭɤɥɟɚɪɧɨɝ ɝɪɚɞɭɫɚ ɭ ɩɨɪɟђɟʃɭ ɫɚ ɨɧɢɦ ɧɢɫɤɨɝ ȾɂɋɄɍɋɂȳȺ 116 ɝɪɚɞɭɫɚ, ɞɨɤ ɡɧɚɱɚʁɧɚ ɤɨɪɟɥɚɰɢʁɚ ɧɢʁɟ ɧɚђɟɧɚ ɢɡɦɟђɭ pT ɫɬɚɞɢʁɭɦɚ ɢ ɟɤɫɩɪɟɫɢʁɟ AQP-146. ɍ ɧɚɲɨʁ ɫɬɭɞɢʁɢ ɧɢɫɦɨ ɨɞɪɟђɢɜɚɥɢ ɬɤɢɜɧɭ ɟɤɫɩɪɟɫɢʁɭ AQP-1 ɢ ʃɟɧɭ ɩɨɜɟɡɚɧɨɫɬ ɫɚ ɤɨɧɰɟɧɬɪɚɰɢʁɨɦ AQP-1 ɭ ɭɪɢɧɭ. ɋ ɨɛɡɢɪɨɦ ɧɚ ɪɟɡɭɥɬɚɬɟ ɧɚɲɟ ɫɬɭɞɢʁɟ, ɦɨɠɟɦɨ ɡɚɤʂɭɱɢɬɢ ɞɚ ɫɟ ELISA ɬɟɫɬ ɧɢʁɟ ɩɨɤɚɡɚɨ ɩɨɭɡɞɚɧɢɦ ɡɚ ɨɞɪɟђɢɜɚʃɟ AQP-1 ɭ ɭɪɢɧɭ. 5.8. Ⱦɢʁɚɝɧɨɫɬɢɱɤɢ ɩɨɬɟɧɰɢʁɚɥ ɩɪɟɨɩɟɪɚɬɢɜɧɢɯ ɜɪɟɞɧɨɫɬɢ ɭɪɢɧɚɪɧɢɯ ɤɨɧɰɟɧɬɪɚɰɢʁɚ KIM-1 ɢ AQP-1 ɡɚ ɤɚɪɰɢɧɨɦ ɫɜɟɬɥɢɯ ʄɟɥɢʁɚ ɛɭɛɪɟɝɚ ɍ ɧɚɲɨʁ ɫɬɭɞɢʁɢ ɫɦɨ ɡɚ ɢɫɩɢɬɢɜɚʃɟ ɞɢʁɚɝɧɨɫɬɢɱɤɨɝ ɩɨɬɟɧɰɢʁɚɥɚ ɩɪɟɨɩɟɪɚɬɢɜɧɢɯ ɚɩɫɨɥɭɬɧɢɯ ɢ ɤɨɪɢɝɨɜɚɧɢɯ ɜɪɟɞɧɨɫɬɢ ɭɪɢɧɚɪɧɟ ɤɨɧɰɟɧɬɪɚɰɢʁɟ KIM-1 (uKIM-1) ɡɚ ɫɄȻ, ɨɞɪɟɞɢɥɢ ɩɨɜɪɲɢɧɭ ɢɫɩɨɞ ROC ɤɪɢɜɟ. ɇɚ ɨɫɧɨɜɭ ɩɨɜɪɲɢɧɟ ɢɫɩɨɞ ROC ɤɪɢɜɟ, ɞɨɛɢɥɢ ɫɦɨ ɞɚ ʁɟ ɞɢʁɚɝɧɨɫɬɢɱɤɢ ɩɨɬɟɧɰɢʁɚɥ ɚɩɫɨɥɭɬɧɟ ɤɨɧɰɟɧɬɪɚɰɢʁɟ uKIM-1 ɡɚ ɞɢʁɚɝɧɨɡɭ ɫɄȻ ɢɡɧɨɫɢɨ 0.84 (0.74-0.93), ɞɨɤ ʁɟ ɨɧ ɡɚ ɤɨɪɢɝɨɜɚɧɭ ɤɨɧɰɟɧɬɪɚɰɢʁɭ uKIM-1 ɢɡɧɨɫɢɨ 0.73 (0.60-0.86). Ⱦɨɛɢʁɟɧ ʁɟ ɫɬɚɬɢɫɬɢɱɤɢ ɡɧɚɱɚʁɚɧ ɞɢʁɚɝɧɨɫɬɢɱɤɢ ɩɨɬɟɧɰɢʁɚɥ ɡɚ ɫɄȻ ɢ ɡɚ ɚɩɫɨɥɭɬɧɭ (p=2.192*10-7) ɢ ɡɚ ɤɨɪɢɝɨɜɚɧɭ (p=0.0008) ɩɪɟɨɩɟɪɚɬɢɜɧɭ ɜɪɟɞɧɨɫɬ ɤɨɧɰɟɧɬɪɚɰɢʁɟ uKIM-1. ɂɡ ɪɟɡɭɥɬɚɬɚ ɧɚɲɟ ɫɬɭɞɢʁɟ ɦɨɠɟɦɨ ɡɚɤʂɭɱɢɬɢ ɞɚ ɨɞɪɟђɢɜɚʃɟ ɚɩɫɨɥɭɬɧɟ ɤɨɧɰɟɧɬɪɚɰɢʁɟ uKIM-1 ɢɦɚ ɜɟʄɢ ɞɢʁɚɝɧɨɫɬɢɱɤɢ ɩɨɬɟɧɰɢʁɚɥ ɡɚ ɞɟɬɟɤɰɢʁɭ ɫɄȻ ɭ ɩɨɪɟђɟʃɭ ɫɚ ɤɨɪɢɝɨɜɚɧɨɦ ɤɨɧɰɟɧɬɪɚɰɢʁɨɦ, ɚɥɢ ɬɚ ɪɚɡɥɢɤɚ ɧɢʁɟ ɫɬɚɬɢɫɬɢɱɤɢ ɡɧɚɱɚʁɧɚ (p=0.107). Morrissey ɢ ɫɚɪ.ɫɭ ɭ ɫɜɨʁɨʁ ɫɬɭɞɢʁɢ ɞɨɛɢɥɢ ɫɤɨɪɨ ɢɧɞɟɧɬɢɱɚɧ ɞɢʁɚɝɧɨɫɬɢɱɤɢ ɩɨɬɟɧɰɢʁɚɥ ɡɚ ɤɨɪɢɝɨɜɚɧɭ ɜɪɟɞɧɨɫɬ uKIM-1 ɤɨʁɢ ʁɟ ɢɡɧɨɫɢɨ 0.75 (p<0.001) ɢ ɨɡɧɚɱɢɥɢ ɫɭ ɝɚ ɤɚɨ ɭɦɟɪɟɧ146. Ⱥɭɬɨɪɢ ɞɪɭɝɢɯ ɫɬɭɞɢʁɚ ɧɢɫɭ ɢɫɩɢɬɢɜɚɥɢ ɞɢʁɚɝɧɨɫɬɢɱɤɢ ɩɨɬɟɧɰɢʁɚɥ ɡɚ ɩɪɟɨɩɟɪɚɬɢɜɧɭ ɞɟɬɟɤɰɢʁɭ ɫɄȻ. Ɂɚ ɩɪɟɨɩɟɪɚɬɢɜɧɟ ɜɪɟɞɧɨɫɬɢ ɭɪɢɧɚɪɧɢɯ ɤɨɧɰɟɧɬɪɚɰɢʁɚ KIM-1 ɢ KIM-1 ɤɨɪɢɝɨɜɚɧɨ, ɢɫɩɢɬɢɜɚɧɟ ɫɭ ɞɢɫɤɪɢɦɢɧɚɰɢɨɧɟ ɜɪɟɞɧɨɫɬɢ ɡɚ ɩɪɢɫɭɫɬɜɨ ɫɄȻ. ɉɪɟɨɩɟɪɚɬɢɜɧɚ ɚɩɫɨɥɭɬɧɚ ɜɪɟɞɧɨɫɬ uKIM-1 ɡɚ ɤɨʁɭ ʁɟ ɩɨɫɬɢɝɧɭɬɚ ɦɚɤɫɢɦɚɥɧɚ ɫɟɧɡɢɬɢɜɧɨɫɬ (64,1%) ɢ ɫɩɟɰɢɮɢɱɧɨɫɬ (95,83%) ɢɡɧɨɫɢɥɚ ʁɟ 0,255 ng/ml. ɉɪɟɨɩɟɪɚɬɢɜɧɚ ɤɨɪɢɝɨɜɚɧɚ ɜɪɟɞɧɨɫɬ uKIM-1 ɡɚ ɤɨʁɭ ʁɟ ɩɨɫɬɢɝɧɭɬɚ ɦɚɤɫɢɦɚɥɧɚ ɫɟɧɡɢɬɢɜɧɨɫɬ (71,79%) ɢ ɫɩɟɰɢɮɢɱɧɨɫɬ (70,83%) ɢɡɧɨɫɢɥɚ ʁɟ 0,226 ng/mgUcr. ɂɡ ɪɟɡɭɥɚɬɚɬɚ ɧɚɲɟɝ ɢɫɩɢɬɢɜɚʃɚ ɦɨɠɟɦɨ ɡɚɤʂɭɱɢɬɢ ɞɚ ɞɨɛɢʁɟɧɚ ɝɪɚɧɢɱɧɚ ɜɪɟɞɧɨɫɬ ɚɩɫɨɥɭɬɧɟ ɤɨɧɰɟɧɬɪɚɰɢʁɟ uKIM-1 ɢɦɚ ɜɢɫɨɤɭ ɫɩɟɰɢɮɢɱɧɨɫɬ ɢ ɭɦɟɪɟɧɭ ɫɟɧɡɢɬɢɜɧɨɫɬ, ɞɨɤ ɤɨɪɢɝɨɜɚɧɚ ɝɪɚɧɢɱɧɚ ɜɪɟɞɧɨɫɬ ɢɦɚ ɭɦɟɪɟɧɭ ɢ ɫɟɧɡɢɬɢɜɧɨɫɬ ɢ ɫɩɟɰɢɮɢɱɧɨɫɬ ɡɚ ɞɢʁɚɝɧɨɡɭ ɫɄȻ. ɍ ɫɬɭɞɢʁɢ Han ɢ ɫɚɪ., ɭɪɢɧɚɪɧɢ ɧɢɜɨ KIM-1 ɜɟʄɢ ɨɞ 0,1 ɢɦɚɨ ʁɟ ɫɟɧɡɢɬɢɜɧɨɫɬ ɨɞ 82% ɢ ɫɩɟɰɢɮɢɱɧɨɫɬ ɨɞ 90%145. Zhang ɢ ɫɚɪ. ɫɭ ɭ ɫɜɨʁɨʁ ɫɬɭɞɢʁɢ ɞɨɛɢɥɢ ɡɧɚɱɚʁɧɨ ɜɢɲɭ ɝɪɚɧɢɱɧɭ ɜɪɟɞɧɨɫɬ ɡɚ ɞɟɬɟɤɰɢʁɭ ɫɄȻ ɨɞɧɨɫɭ ɧɚ ɧɚɲɟ ɜɪɟɞɧɨɫɬɢ148. Ɉɧɚ ʁɟ ɢɡɧɨɫɢɥɚ 1.0 ng/mgUcr ɢ ɢɦɚɥɚ ʁɟ ɫɩɟɰɢɮɢɱɧɨɫɬ 100% ɢɪɟɥɚɬɢɜɧɨ ɧɢɫɤɭ ɫɟɧɡɢɬɢɜɧɨɫɬ ɤɨʁɚ ʁɟ ɢɡɧɨɫɢɥɚ 50%. ɍ ɧɚɲɨʁ ɫɬɭɞɢʁɢ ɫɩɪɨɜɟɥɢ ɫɦɨ ɢɫɩɢɬɢɜɚʃɟ ɞɢʁɚɝɧɨɫɬɢɱɤɨɝ ɩɨɬɟɧɰɢʁɚɥɚ ɩɪɟɨɩɟɪɚɬɢɜɧɢɯ ɚɩɫɨɥɭɬɧɢɯ ɢ ɤɨɪɢɝɨɜɚɧɢɯ ɜɪɟɞɧɨɫɬɢ ɭɪɢɧɚɪɧɟ ɤɨɧɰɟɧɬɪɚɰɢʁɟ AQP-1(uAQP-1) ɡɚ ɞɢʁɚɝɧɨɡɭ ɫɄȻ. ɇɚ ɨɫɧɨɜɭ ɩɨɜɪɲɢɧɟ ɢɫɩɨɞ ROC ɤɪɢɜɟ, ɞɨɛɢɥɢ ɫɦɨ ɞɚ ʁɟ ɞɢʁɚɝɧɨɫɬɢɱɤɢ ɩɨɬɟɧɰɢʁɚɥ ɚɩɫɨɥɭɬɧɟ ɤɨɧɰɟɧɬɪɚɰɢʁɟ uAQP-1 ɡɚ ɞɢʁɚɝɧɨɡɭ ɫɄȻ ɢɡɧɨɫɢɨ 0.50 (0.34-0.65), ɞɨɤ ʁɟ ɨɧ ɡɚ ɤɨɪɢɝɨɜɚɧɭ ɤɨɧɰɟɧɬɪɚɰɢʁɭ uAQP-1 ɢɡɧɨɫɢɨ 0.66 (0.52-0.81). Ⱦɨɛɢʁɟɧ ʁɟ ȾɂɋɄɍɋɂȳȺ 117 ɫɬɚɬɢɫɬɢɱɤɢ ɡɧɚɱɚʁɚɧ ɞɢʁɚɝɧɨɫɬɢɱɤɢ ɩɨɬɟɧɰɢʁɚɥ ɤɨɪɢɝɨɜɚɧɟ ɤɨɧɰɟɧɬɪɚɰɢʁɟ uAQP-1 (p=0.03) ɡɚ ɞɢʁɚɝɧɨɡɭ ɫɄȻ, ɞɨɤ ɡɚ ɚɩɫɨɥɭɬɧɭ ɤɨɧɰɟɧɬɪɚɰɢʁɭ uAQP-1 ɧɢʁɟ ɞɨɛɢʁɟɧ ɫɬɚɬɢɫɬɢɱɤɢ ɡɧɚɱɚʁɚɧ ɞɢʁɚɝɧɨɫɬɢɱɤɢ ɩɨɬɟɧɰɢʁɚɥ (p=0.680). ɉɨɪɟђɟʃɟɦ ɞɢʁɚɝɧɨɫɬɢɱɤɨɝ ɩɨɬɟɧɰɢʁɚɥɚ ɩɪɟɨɩɟɪɚɬɢɜɧɢɯ ɚɩɫɨɥɭɬɧɢɯ ɢ ɤɨɪɢɝɨɜɚɧɢɯ ɤɨɧɰɟɧɬɪɚɰɢʁɚ uAQP-1, ɞɨɛɢʁɟɧɚ ʁɟ ɫɬɚɬɢɱɤɢ ɡɧɚɱɚʁɧɚ ɪɚɡɥɢɤɚ (p=0.0464). ɇɚ ɨɫɧɨɜɭ ɪɟɡɭɥɚɬɚɬɚ ɧɚɲɟɝ ɢɫɩɢɬɢɜɚʃɟ ɦɨɠɟ ɫɟ ɡɚɤʂɭɱɢɬɢ ɞɚ ɫɚɦɨ ɤɨɪɢɝɨɜɚɧɚ ɤɨɧɰɟɧɬɪɚɰɢʁɚ uAQP-1 ɢɦɚ ɞɢʁɚɝɧɨɫɬɢɱɤɢ ɩɨɬɟɧɰɢʁɚɥ ɡɚ ɞɟɬɟɤɰɢʁɭ ɫɄȻ. ɍ ɫɬɭɞɢʁɚɦɚ Morrissey ɢ ɫɚɪ. ɤɨɧɰɟɧɬɪɚɰɢʁɚ AQP-1 ɭ ɭɪɢɧɭ ɨɞɪɟђɟɧɚ Western blot ɬɟɯɧɢɤɨɦ, ɢɦɚɥɚ ʁɟ ɫɩɟɰɢɮɢɱɧɨɫɬ ɢ ɫɟɧɡɢɬɢɜɧɨɫɬ ɡɚ ɞɢʁɚɝɧɨɡɭ ɫɄȻ ɨɞ 99% ɞɨ 100%160. ɍ ɧɚɲɨʁ ɫɬɭɞɢʁɢ ɫɦɨ ɩɨɤɚɡɚɥɢ ɭɦɟɪɟɧɭ ɫɟɧɡɢɬɢɜɧɨɫɬ ɢ ɫɩɟɰɢɮɢɱɧɨɫɬ (66%) ɤɨɪɢɝɨɜɚɧɟ ɤɨɧɰɟɧɬɪɚɰɢʁɟ uAQP-1 ɡɚ ɞɢʁɚɝɧɨɡɭ ɫɄȻ, ɞɨɤ ʁɟ ɨɧɚ ɡɚ ɚɩɫɨɥɭɬɧɭ ɤɨɧɰɟɧɬɪɚɰɢʁɭ ɛɢɥɚ ɪɟɥɚɬɢɜɧɨ ɧɢɫɤɚ ɢ ɢɡɧɨɫɢɥɚ ʁɟ 50%. ɇɚɜɟɞɟɧɟ ɪɚɡɥɢɤɟ ɭ ɫɟɧɡɢɬɢɜɧɨɫɬɢ ɢ ɫɩɟɰɢɮɢɱɧɨɫɬɢ ɢɡɦɟђɭ ɧɚɲɟɝ ɢ ɪɚɧɢʁɟ ɫɩɪɨɜɟɞɧɢɯ ɢɫɩɢɬɢɜɚʃɚ ɫɭ ɧɚʁɜɟɪɨɜɚɬɧɢʁɟ ɜɟɡɚɧɟ ɡɚ ɧɚɱɢɧ ɨɞɪɟђɢɜɚʃɚ ɤɨɧɰɟɧɬɪɚɰɢʁɟ uAQP-1. ɉɪɟɦɚ ɧɚɦɚ ɞɨɫɬɭɩɧɢɦ ɩɨɞɚɰɢɦɚ, ɭ ɧɚɲɨʁ ɫɬɭɞɢʁɢ ʁɟ ɩɪɜɢ ɩɭɬ ɩɪɢɦɟʃɟɧ ɤɨɦɟɪɰɢʁɚɥɧɢ ELISA ɬɟɫɬ ɡɚ ɤɜɚɧɬɢɬɚɬɢɜɧɨ ɨɞɪɟђɢɜɚʃɟ ɨɜɨɝ ɭɪɢɧɚɪɧɨɝ ɛɢɨɦɚɪɤɟɪɚ, ɞɨɤ ɫɭ ɚɭɬɨɪɢ ɧɚɜɟɞɟɧɢɯ ɫɬɭɞɢʁɚ ɤɨɪɢɫɬɢɥɢ ɫɟɧɡɢɬɢɜɚɧ ɢ ɫɩɟɰɢɮɢɱɚɧ Western blot ɬɟɫɬ ɩɪɨɢɡɜɟɞɟɧ ɭ ɫɨɩɫɬɜɟɧɨʁ ɥɚɛɨɪɚɬɨɪɢʁɢ. ɉɪɟɨɩɟɪɚɬɢɜɧɚ ɚɩɫɨɥɭɬɧɚ ɜɪɟɞɧɨɫɬ uAQP-1ɡɚ ɤɨʁɭ ʁɟ ɩɨɫɬɢɝɧɭɬɚ ɦɚɤɫɢɦɚɥɧɚ ɫɟɧɡɢɬɢɜɧɨɫɬ (79,49%) ɢ ɫɩɟɰɢɮɢɱɧɨɫɬ (31,75%) ɢɡɧɨɫɢɥɚ ʁɟ 0,094 ng/ml. ɉɪɟɨɩɟɪɚɬɢɜɧɚ ɤɨɪɢɝɨɜɚɧɚ ɜɪɟɞɧɨɫɬ uAQP-1ɡɚ ɤɨʁɭ ʁɟ ɩɨɫɬɢɝɧɭɬɚ ɦɚɤɫɢɦɚɥɧɚ ɫɟɧɡɢɬɢɜɧɨɫɬ (56,41%) ɢ ɫɩɟɰɢɮɢɱɧɨɫɬ (75%) ɢɡɧɨɫɢɥɚ ʁɟ 0,081 ng/mgUcr. ɂɡ ɪɟɡɭɥɚɬɚɬɚ ɧɚɲɟɝ ɢɫɩɢɬɢɜɚʃɚ ɦɨɠɟɦɨ ɡɚɤʂɭɱɢɬɢ ɞɚ ɞɨɛɢʁɟɧɚ ɝɪɚɧɢɱɧɚ ɜɪɟɞɧɨɫɬ ɚɩɫɨɥɭɬɧɟ ɤɨɧɰɟɧɬɪɚɰɢʁɟ uAQP-1 ɢɦɚ ɭɦɟɪɟɧɭ ɫɟɧɡɢɬɢɜɧɨɫɬ ɚɥɢ ɦɚɥɭ ɫɩɟɰɢɮɢɱɧɨɫɬ, ɞɨɤ ɤɨɪɢɝɨɜɚɧɚ ɝɪɚɧɢɱɧɚ ɜɪɟɞɧɨɫɬ ɢɦɚ ɭɦɟɪɟɧɭ ɢ ɫɟɧɡɢɬɢɜɧɨɫɬ ɢ ɫɩɟɰɢɮɢɱɧɨɫɬ. Ʉɚɞɚ ɫɦɨ ɦɟђɭɫɨɛɧɨ ɭɩɨɪɟɞɢɥɢ ɞɢʁɚɝɧɨɫɬɢɱɤɢ ɩɨɬɟɧɰɢʁɚɥ ɩɪɟɨɩɟɪɚɬɢɜɧɢɯ ɚɩɫɨɥɭɬɧɢɯ ɢ ɤɨɪɢɝɨɜɚɧɢɯ ɜɪɟɞɧɨɫɬɢ ɨɜɚ ɞɜɚ ɭɪɢɧɚɪɧɚ ɛɢɨɦɚɪɤɟɪɚ ɡɚ ɞɟɬɟɤɰɢʁɭ ɫɄȻ, ɧɢʁɟ ɞɨɛɢʁɟɧɚ ɫɬɚɬɢɫɬɢɱɤɢ ɡɧɚɱɚʁɧɚ ɪɚɡɥɢɤɚ ɭ ɞɢʁɚɝɧɨɫɬɢɱɤɨɦ ɩɨɬɟɧɰɢʁɚɥɭ ɫɚɦɨ ɢɡɦɟђɭ ɜɪɟɞɧɨɫɬɢ ɤɨɪɢɝɨɜɚɧɢɯ ɤɨɧɰɟɧɬɪɚɰɢʁɚ uKIM-1 ɢ uAQP-1. ɉɨɪɟђɟʃɟɦ ɨɫɬɚɥɢɯ ɩɚɪɨɜɚ ɩɚɪɚɦɟɬɚɪɚ ɪɚɡɥɢɱɢɬɨɝ ɬɢɩɚ (uKIM-1 ɧɚɫɭɩɪɨɬ uAQP-1, uKIM-1 ɧɚɫɭɩɪɨɬ uAQP-1 ɤɨɪɢɝɨɜɚɧɨ,uKIM-1 ɤɨɪɢɝɨɜɚɧɨ ɧɚɫɭɩɪɨɬ uAQP-1), ɞɨɛɢʁɟɧɚ ʁɟ ɫɬɚɬɢɫɬɢɱɤɢ ɡɧɚɱɚʁɧɚ ɪɚɡɥɢɤɚ ɭ ɞɢʁɚɝɧɨɫɬɢɱɤɨɦ ɩɨɬɟɧɰɢʁɚɥɭ. Ɋɟɡɭɥɬɚɬɢ ɧɚɲɟɝ ɢɫɩɢɬɢɜɚʃɚ ɫɭ ɩɨɤɚɡɚɥɢ ɞɚ ɚɩɫɨɥɭɬɧɚ ɤɨɧɰɟɧɬɪɚɰɢʁɚ uKIM- 1 ɢɦɚ ɫɬɚɬɢɫɬɢɱɤɢ ɡɧɚɱɚʁɧɨ ɜɟʄɢ ɞɢʁɚɝɧɨɫɬɢɱɤɢ ɩɨɬɟɧɰɢʁɚɥ ɡɚ ɞɟɬɟɤɰɢʁɭ ɫɄȻ ɭ ɨɞɧɨɫɭ ɢ ɧɚ ɚɩɫɨɥɭɬɧɭ ɢ ɧɚ ɤɨɪɢɝɨɜɚɧɭ ɤɨɧɰɟɧɬɪɚɰɢʁɭ uAQP-1, ɞɨɤ ɤɨɪɢɝɨɜɚɧɚ ɤɨɧɰɟɧɬɪɚɰɢʁɚ uKIM-1 ɢɦɚ ɫɬɚɬɢɫɬɢɱɤɢ ɡɧɚɱɚʁɧɨ ɜɟʄɢ ɞɢʁɚɝɧɨɫɬɢɱɤɢ ɩɨɬɟɧɰɢʁɚɥ ɫɚɦɨ ɭ ɨɞɧɨɫɭ ɧɚ ɚɩɫɨɥɭɬɧɭ ɜɪɟɞɧɨɫɬ uAQP-1. ɉɪɟɦɚ ɧɚɲɢɦ ɫɚɡɧɚʃɢɦɚ ɧɟ ɩɨɫɬɨʁɟ ɫɬɭɞɢʁɟ ɤɨʁɟ ɫɭ ɩɨɪɟɞɢɥɟ ɞɢʁɚɝɧɨɫɬɢɱɤɢ ɩɨɬɟɧɰɢʁɚɥ ɨɜɚ ɞɜɚ ɭɪɢɧɚɪɧɚ ɛɢɨɦɚɪɤɟɪɚ ɡɚ ɞɢʁɚɝɧɨɡɭ ɫɄȻ, ɩɪɢ ɱɟɦɭ ʁɟ ɤɨɧɰɟɧɬɪɚɰɢʁɚ ɨɛɚ ɛɢɨɦɚɪɤɟɪɚ ɨɞɪɟђɟɧɚ ɩɪɢɦɟɧɨɦ ELISA ɬɟɫɬɚ. ɁȺɄȴɍɑɐɂ 118 6.ɁȺɄȴɍɑɐɂ ɇɚ ɨɫɧɨɜɭ ɢɡɧɟɬɢɯ ɪɟɡɭɥɬɚɬɚ ɦɨɝɭ ɫɟ ɢɡɜɟɫɬɢ ɫɥɟɞɟʄɢ ɡɚɤʂɭɱɰɢ: 1. Ɉɞɪɟђɢɜɚʃɟ ɤɨɧɰɟɧɬɪɚɰɢʁɟ KIM-1ɭ ɭɪɢɧɭ ɤɨɞ ɩɚɰɢʁɟɧɚɬɚ ɫɚ ɤɥɢɧɢɱɤɢ ɢ ɦɨɪɮɨɥɨɲɤɢ ɩɨɫɬɚɜʂɟɧɨɦ ɫɭɦʃɨɦ ɧɚ ɩɨɫɬɨʁɚʃɟ ɤɚɪɰɢɧɨɦɚ ɫɜɟɬɥɢɯ ʄɟɥɢʁɚ ɛɭɛɪɟɝɚ, ɩɪɟɞɫɬɚɜʂɚ ɫɟɧɡɢɬɢɜɚɧ ɢ ɫɩɟɰɢɮɢɱɚɧ ɬɟɫɬ ɡɚ ɩɪɟɨɩɟɪɚɬɢɜɧɭ ɞɢʁɚɝɧɨɡɭ ɛɨɥɟɫɬɢ. 2. Ʉɨɧɰɟɧɬɪɚɰɢʁɚ KIM-1ɭ ɭɪɢɧɭ ɫɬɚɬɢɫɬɢɱɤɢ ɡɧɚɱɚʁɧɨ ɤɨɪɟɥɢɪɚ ɫɚ ɫɬɚɞɢʁɭɦɨɦ ɢ ɝɪɚɞɭɫɨɦ ɬɭɦɨɪɚ. 3. Ʉɨɧɰɟɧɬɪɚɰɢʁɚ KIM-1 ɭ ɭɪɢɧɭ ɩɚɰɢʁɟɧɚɬɚ ɫɚ ɬɭɦɨɪɫɤɨɦ ɩɪɨɦɟɧɨɦ ≤4 cm ʁɟ ɡɧɚɱɚʁɧɨ ɜɢɲɚ ɭ ɨɞɧɨɫɭ ɧɚ ʃɟɝɨɜɭ ɤɨɧɰɟɧɬɪɚɰɢʁɭ ɭ ɭɪɢɧɭ ɡɞɪɚɜɢɯ ɨɫɨɛɚ ɢ ɩɪɟɞɫɬɚʂɚ ɞɨɞɚɬɧɢ ɞɢʁɚɝɧɨɫɬɢɱɤɢ ɬɟɫɬ ɡɚ ɭɬɜɪђɢɜɚʃɟ ɩɪɢɪɨɞɟ ɦɚɥɢɯ ɬɭɦɨɪɫɤɢɯ ɩɪɨɦɟɧɚ. 4. ɉɨɪɟђɟʃɟɦ ɤɨɧɰɟɧɬɪɚɰɢʁɚ KIM-1 ɭ ɭɪɢɧɭ ɢɡɪɚɠɟɧɢɦ ɭ ɚɩɫɨɥɭɬɧɢɦ ɢ ɤɨɪɢɝɨɜɚɧɢɦ ɜɪɟɞɧɨɫɬɢɦɚ, ɧɢʁɟ ɩɨɤɚɡɚɧɚ ɫɬɚɬɢɫɬɢɱɤɢ ɡɧɚɱɚʁɧɚ ɪɚɡɥɢɤɚ ɭ ɞɢʁɚɝɧɨɫɬɢɱɤɨɦ ɩɨɬɟɧɰɢʁɚɥɭ. 5. ɉɨɫɬɨɩɟɪɚɬɢɜɧɨ ɩɨɜɟʄɚʃɟ ɤɨɧɰɟɧɬɪɚɰɢʁɟ KIM-1 ɭ ɭɪɢɧɭ ɩɚɰɢʁɟɧɚɬɚ ɫɚ ɩɚɪɰɢʁɚɥɧɨɦ ɧɟɮɪɟɤɬɨɦɢʁɨɦ ʁɟ ɩɨɫɥɟɞɢɰɚ ɢɫɯɟɦɢʁɫɤɨɝ ɨɲɬɟʄɟʃɚ. 6. Ɍɤɢɜɧɚ ɟɤɫɩɪɟɫɢʁɚ KIM-1 ɫɬɚɬɢɫɬɢɱɤɢ ɡɧɚɱɚʁɧɨ ɤɨɪɟɥɢɪɚ ɫɚ ɫɬɚɞɢʁɭɦɨɦ ɬɭɦɨɪɚ ɢ ɜɢɫɨɤɨ ɤɨɪɟɥɢɪɚ ɫɚ ɝɪɚɞɭɫɨɦ ɬɭɦɨɪɚ ɚɥɢ ɛɟɡ ɫɬɚɬɢɫɬɢɱɤɟ ɡɧɚɱɚʁɧɨɫɬɢ. 7. Ɉɞɪɟђɢɜɚʃɟ ɤɨɧɰɟɧɬɪɚɰɢʁɟ AQP-1 ɭ ɭɪɢɧɭ ɩɪɟɞɫɬɚɜʂɚ ɧɟɞɨɜɨʂɧɨ ɫɟɧɡɢɬɢɜɚɧ ɢ ɫɩɟɰɢɮɢɱɚɧ ɬɟɫɬ ɡɚ ɞɢʁɚɝɧɨɡɭ ɤɚɪɰɢɧɨɦɚ ɫɜɟɬɥɢɯ ʄɟɥɢʁɚ ɛɭɛɪɟɝɚ. ɅɂɌȿɊȺɌɍɊȺ 119 ɅɂɌȿɊȺɌɍɊȺ 1Judd SE. Carcinoma of the renal cortex with factors bearing on prognosis. Archives of Internal Medicine 1929; 44: 746. 2Foot NC, Humphreys GA, Whitmore WF. 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Дɨкɬɨɪɫкɚ ɞиɫɟɪɬɚцијɚ ɇɚɫɥɨɜ: Ⱦɢʁɚɝɧɨɫɬɢɱɤɢ ɡɧɚɱɚʁ ɩɪɨɬɟɢɧɚ ɨɲɬɟʄɟʃɚ ɛɭɛɪɟɝɚ-1 (KIM-1) ɢ ɚɤɜɚɩɨɪɢɧɚ 1 (AQP-1)ɤɨɞ ɛɨɥɟɫɧɢɤɚ ɤɨʁɢ ɛɨɥɭʁɭ ɨɞ ɤɚɪɰɢɧɨɦɚ ɫɜɟɬɥɢɯ ʄɟɥɢʁɚ ɛɭɛɪɟɝɚ Ȼɪɨʁ ɫɬɪɚɧɢɰɚ: 130 Ȼɪɨʁ ɫɥɢɤɚ:21, ɛɪɨʁ ɬɚɛɟɥɚ:111, ɛɪɨʁ ɝɪɚɮɢɤɨɧɚ:14 Ȼɪɨʁ ɛɢɛɥɢɨɝɪɚɮɫɤɢɯ ɩɨɞɚɬɚɤɚ: 251 ɍɫɬɚɧɨɜɚ ɢ ɦɟɫɬɨ ɝɞɟ ʁɟ ɪɚɞ ɢɡɪɚђɟɧ: ȼɨʁɧɨɦɟɞɢɰɢɧɫɤɚ ɚɤɚɞɟɦɢʁɚ, Ȼɟɨɝɪɚɞ, ɋɪɛɢʁɚ (Ʉɥɢɧɢɤɚ ɡɚ ɭɪɨɥɨɝɢʁɭ, Ɉɞɟʂɟʃɟ ɡɚ ɤɥɢɧɢɱɤɭ ɢ ɟɤɫɩɟɪɢɦɟɧɬɚɥɧɭ ɢɦɭɧɨɥɨɝɢʁɭ ɂɧɫɬɢɬɭɬɚ ɡɚ ɦɟɞɢɰɢɧɫɤɚ ɢɫɬɪɚɠɢɜɚʃɚ ɢ ɂɧɫɬɢɬɭɬ ɡɚ ɩɚɬɨɥɨɝɢʁɭ ɢ ɫɭɞɫɤɭ ɦɟɞɢɰɢɧɭ) ɇɚɭɱɧɚ ɨɛɥɚɫɬ (ɍȾɄ): Ɇɟɞɢɰɢɧɚ (Ʉɥɢɧɢɱɤɚ ɢ ɟɤɫɩɟɪɢɦɟɧɬɚɥɧɚ ɢɧɬɟɪɧɚ ɦɟɞɢɰɢɧɚ) Ɇɟɧɬɨɪ:ɉɪɨɮ. ɞɪ Ⱦɟʁɚɧ ɉɟɬɪɨɜɢʄ III. Оцɟɧɚ и ɨɞɛɪɚɧɚ Ⱦɚɬɭɦ ɩɪɢʁɚɜɟ ɬɟɦɟ: 07.02.2013. ɝɨɞ. Ȼɪɨʁ ɨɞɥɭɤɟ ɢ ɞɚɬɭɦɩɪɢɯɜɚɬɚʃɚɞɨɤɬɨɪɫɤɟɞɢɫɟɪɬɚɰɢʁɟ: 01-4869/3-10 ɨɞ 29.05.2013. ɝɨɞ. Ʉɨɦɢɫɢʁɚ ɡɚ ɨɰɟɧɭ ɩɨɞɨɛɧɨɫɬɢ ɬɟɦɟ ɢ ɤɚɧɞɢɞɚɬɚ: ɉɪɨɮ. Ⱦɪ Ⱦɟʁɚɧ ɉɟɬɪɨɜɢʄ ɉɪɨɮ. Ⱦɪ ɇɨɜɚɤ Ɇɢɥɨɜɢʄ ɉɪɨɮ. Ⱦɪ ɋɧɟɠɚɧɚ ɐɟɪɨɜɢʄ Ʉɨɦɢɫɢʁɚ ɡɚ ɨɰɟɧɭ ɞɨɤɬɨɪɫɤɟ ɞɢɫɟɪɬɚɰɢʁɟ: ɉɪɨɮ. Ⱦɪ ɋɧɟɠɚɧɚ ɀɢɜɚɧɱɟɜɢʄ-ɋɢɦɨɧɨɜɢʄ, ɩɪɟɞɫɟɞɧɢɤ ɉɪɨɮ. Ⱦɪ ɇɨɜɚɤ Ɇɢɥɨɜɢʄ, ɱɥɚɧ ɉɪɨɮ. Ⱦɪ ɋɧɟɠɚɧɚ ɐɟɪɨɜɢʄ, ɱɥɚɧ Ʉɨɦɢɫɢʁɚ ɡɚ ɨɞɛɪɚɧɭ ɞɨɤɬɨɪɫɤɟ ɞɢɫɟɪɬɚɰɢʁɟ: ɉɪɨɮ. Ⱦɪ ɋɧɟɠɚɧɚ ɀɢɜɚɧɱɟɜɢʄ-ɋɢɦɨɧɨɜɢʄ, ɩɪɟɞɫɟɞɧɢɉɪɨɮ. Ⱦɪ ɇɨɜɚɤ Ɇɢɥɨɜɢʄ, ɱɥɚɧ ɉɪɨɮ. Ⱦɪ ɋɧɟɠɚɧɚ ɐɟɪɨɜɢʄ, ɱɥɚɧ Ⱦɚɬɭɦ ɨɞɛɪɚɧɟ ɞɢɫɟɪɬɚɰɢʁɟ: ɍɇɂȼȿɊɁɂɌȿɌ ɍ ɄɊȺȽɍȳȿȼɐɍ, ɎȺɄɍɅɌȿɌ ɆȿȾɂɐɂɇɋɄɂɏ ɇȺɍɄȺ ɄȴɍɑɇȺ ȾɈɄɍɆȿɇɌȺɐɂȳɋɄȺ ɂɇɎɈɊɆȺɌɂɄȺ Ɋɟɞɧɢ ɛɪɨʁ ɂɞɟɧɬɢɮɢɤɚɰɢɨɧɢ ɛɪɨʁ - ɂȻɊ Ɍɢɩ ɞɨɤɭɦɟɧɬɚɰɢʁɟ - ɌȾ Ɇɨɧɨɝɪɚɮɫɤɚ ɩɭɛɥɢɤɚɰɢʁɚ Ɍɢɩ ɡɚɩɢɫɚ Ɍɟɤɫɬɭɚɥɧɢ ɲɬɚɦɩɚɧɢ ɦɚɬɟɪɢʁɚɥ ȼɪɫɬɚ ɪɚɞɚ - ȼɊ Ⱦɨɤɬɨɪɫɤɚ ɞɢɫɟɪɬɚɰɢʁɚ Ⱥɭɬɨɪ - Ⱥɍ Ɇɢɪʁɚɧɚ Ɇɢʁɭɲɤɨɜɢʄ Ɇɟɧɬɨɪ - Ɇɇ Ⱦɟʁɚɧ ɉɟɬɪɨɜɢʄ ɇɚɫɥɨɜ ɪɚɞɚ Ⱦɢʁɚɝɧɨɫɬɢɱɤɢ ɡɧɚɱɚʁ ɩɪɨɬɟɢɧɚ ɨɲɬɟʄɟʃɚ ɛɭɛɪɟɝɚ-1 (KIM-1) ɢ ɚɤɜɚɩɨɪɢɧɚ 1 (AQP-1) ɤɨɞ ɛɨɥɟɫɧɢɤɚ ɤɨʁɢ ɛɨɥɭʁɭ ɨɞ ɤɚɪɰɢɧɨɦɚ ɫɜɟɬɥɢɯ ʄɟɥɢʁɚ ɛɭɛɪɟɝɚ ȳɟɡɢɤ ɩɭɛɥɢɤɚɰɢʁɟ - ȳɉ ɋɪɩɫɤɢ (ʄɢɪɢɥɢɰɚ) ȳɟɡɢɤ ɢɡɜɨɞɚ - ȳɂ ɋɪɩɫɤɢ / ȿɧɝɥɟɫɤɢ Ɂɟɦʂɚ ɩɭɛɥɢɤɨɜɚʃɚ - Ɂɉ ɋɪɛɢʁɚ ɍɠɟ ɝɟɨɝɪɚɮɫɤɨ ɩɨɞɪɭɱʁɟ - ɍȽɉ ɒɭɦɚɞɢʁɚ Ƚɨɞɢɧɚ - ȽɈ 2015. ɂɡɞɚɜɚɱ - ɂɁ Ⱥɭɬɨɪɫɤɢ ɪɟɩɪɢɧɬ Ɇɟɫɬɨ ɢ ɚɞɪɟɫɚ - Ɇɋ 34000 Ʉɪɚɝɭʁɟɜɚɰ, ɋɜɟɬɨɡɚɪɚ Ɇɚɪɤɨɜɢʄɚ 69 Ɏɢɡɢɱɤɢ ɨɩɢɫ ɪɚɞɚ - ɎɈ Ⱦɢɫɟɪɬɚɰɢʁɚ ɢɦɚ 130 ɫɬɪɚɧɚ, 7 ɩɨɝɥɚɜʂɚ, 111 ɬɚɛɟɥɚ, 14 ɝɪɚɮɢɤɨɧɚ ɢ 251 ɰɢɬɢɪɚɧɭ ɛɢɛɥɢɨɝɪɚɮɫɤɭ ʁɟɞɢɧɢɰɭ ɇɚɭɱɧɚ ɨɛɥɚɫɬ - ɇɈ Ɇɟɞɢɰɢɧɚ ɇɚɭɱɧɚ ɞɢɫɰɢɩɥɢɧɚ - Ⱦɂ Ʉɥɢɧɢɱɤɚ ɢ ɟɤɫɩɟɪɢɦɟɧɬɚɥɧɚ ɢɧɬɟɪɧɚ ɦɟɞɢɰɢɧɚ ɉɪɟɞɦɟɬɧɚ ɨɞɪɟɞɧɢɰɚ / ɤʂɭɱɧɟ ɪɟɱɢ - ɉɈ ɍɪɢɧɚɪɧɢ ɛɢɨɦɚɪɤɟɪ, KIM-1, AQP-1, ɞɢʁɚɝɧɨɫɬɢɱɤɢ ɡɧɚɱɚʁ, ɤɚɪɰɢɧɨɦ ɫɜɟɬɥɢɯ ʄɟɥɢʁɚ ɛɭɛɪɟɝɚ ɍȾɄ ɑɭɜɚ ɫɟ - ɑɍ ɍ ɛɢɛɥɢɨɬɟɰɢ Ɇɟɞɢɰɢɧɫɤɨɝ Ɏɚɤɭɥɬɟɬɚ ɍɧɢɜɟɪɡɢɬɟɬɚ ɭ Ʉɪɚɝɭʁɟɜɰɭ, ɋɪɛɢʁɚ ȼɚɠɧɚ ɧɚɩɨɦɟɧɚ - ȼɇ ɂɡɜɨɞ - ɂȾ Ʉɚɪɰɢɧɨɦ ɛɭɛɪɟɝɚ (ɄȻ) ɱɢɧɢ ɩɪɢɛɥɢɠɧɨ 3,8% ɨɞ ɭɤɭɩɧɨɝ ɛɪɨʁɚ ɦɚɥɢɝɧɢɬɟɬɚ ɤɨɞ ɨɞɪɚɫɥɢɯ, ɩɨɤɚɡɭʁɭʄɢ ɤɨɧɫɬɚɧɬɚɧ ɩɨɪɚɫɬ ɩɨɫɥɟɞʃɢɯ 30 ɝɨɞɢɧɚ. ɇɚʁɱɟɲʄɢ ɢ ɧɚʁɚɝɪɟɫɢɜɧɢʁɢ ɩɨɞɬɢɩ ɄȻ ʁɟ ɫɜɟɬɥɨʄɟɥɢʁɫɤɢ ɤɚɪɰɢɧɨɦ ɛɭɛɪɟɝɚ (ɫɄȻ), ɤɨʁɢ ɫɟ ɱɟɫɬɨ ɤɚɪɚɤɬɟɪɢɲɟ ɨɞɫɭɫɬɜɨɦ ɪɚɧɢɯ ɫɢɦɩɬɨɦɚ ɢ ɡɧɚɤɨɜɚ ɛɨɥɟɫɬɢ, ɤɚɨ ɢ ɥɚɛɨɪɚɬɨɪɢʁɫɤɢɯ ɚɛɧɨɪɦɚɥɧɨɫɬɢ. ɉɨɭɡɞɚɧ ɭɪɢɧɚɪɧɢ ɬɟɫɬ ɡɚ ɫɄȻ ɦɨɝɚɨ ɛɢ ɞɚ ɢɦɚ ɡɧɚɱɚʁ ɭ ɩɪɟɨɩɟɪɚɬɢɜɧɨʁ ɞɢʁɚɝɧɨɡɢ ɨɜɨɝ ɬɭɦɨɪɚ ɢ ɤɚɨ ɞɨɞɚɬɧɢ ɦɚɪɤɟɪ ɡɚ ɨɞɝɨɜɨɪ ɧɚ ɬɟɪɚɩɢʁɭ ɢ ɩɨɫɬ- ɬɟɪɚɩɢʁɫɤɨ ɩɪɚʄɟʃɟ. ɋɩɪɨɜɟɞɟɧɚ ɢɫɩɢɬɢɜɚʃɚ ɫɭ ɭɤɚɡɚɥɚ ɧɚ ɩɨɜɟʄɚɧɭ ɟɤɫɩɪɟɫɢʁɭ ɨɞɪɟђɟɧɢɯ ɩɪɨɬɟɢɧɚ ɭ ɬɭɦɨɪɫɤɨɦ ɬɤɢɜɭ ɫɄȻ. ɇɚ ɨɫɧɨɜɭ ɩɨɬɟɧɰɢʁɚɥɚ ɡɚ ɭɪɢɧɚɪɧɭ ɟɤɫɤɪɟɰɢʁɭ ɨɜɢɯ ɭɫɯɨɞɧɨ ɪɟɝɭɥɢɫɚɧɢɯ ɩɪɨɬɟɢɧɚ, ɤɚɨ ɢ ɫɟɧɡɢɬɢɜɧɨɫɬɢ ɢ ɫɩɟɰɢɮɢɱɧɨɫɬɢ ɡɚ ɞɢʁɚɝɧɨɡɭ ɫɄȻ, ɢɡɞɜɨʁɢɥɢ ɫɭ ɫɟ ɩɪɨɬɟɢɧ 1 ɨɲɬɟʄɟʃɚ ɛɭɛɪɟɝɚ (KIM-1) ɢ ɚɤɜɚɩɨɪɢɧ 1 (AQP-1). ɐɢʂ ɫɬɭɞɢʁɟ ʁɟ ɛɢɨ ɞɚ ɫɟ ɢɫɩɢɬɚ ɩɨɬɟɧɰɢʁɚɥ KIM-1 ɢ AQP-1 ɡɚ ɞɢʁɚɝɧɨɡɭ ɫɄȻ, ɩɨɫɟɛɧɨ ɬɭɦɨɪɫɤɢɯ ɩɪɨɦɟɧɚ ɩɪɨɦɟɪɚ ɞɨ 4 МЦ, ɤɚɨ ɢ ɩɨɜɟɡɚɧɨɫɬ ʃɢɯɨɜɟ ɤɨɧɰɟɧɬɪɚɰɢʁɟ ɭ ɭɪɢɧɭ ɫɚ ɯɢɫɬɨɥɨɲɤɢɦ ɤɚɪɚɤɬɟɪɢɫɬɢɤɚɦɚ ɬɭɦɨɪɚ. ɍ ɫɬɭɞɢʁɭ ʁɟ ɛɢɨ ɭɤʂɭɱɟɧ 41 ɩɚɰɢʁɟɧɬ (26 ɦɭɲɤɚɪɚɰɚ, 15 ɠɟɧɚ), ɤɨɞ ɤɨʁɢɯ ʁɟ ɧɚɤɨɧ ɩɚɪɰɢʁɚɥɧɟ ɢɥɢ ɪɚɞɢɤɚɥɧɟ ɧɟɮɪɟɤɬɨɦɢʁɟ ɩɨɫɬɚɜʂɟɧɚ ɞɢʁɚɝɧɨɡɚ ɫɄȻ. Ʉɨɧɬɪɨɥɧɭ ɝɪɭɩɭ ɱɢɧɢɥɨ ʁɟ 40 ɡɞɪɚɜɢɯ ɢɫɩɢɬɚɧɢɤɚ. Ʉɨɧɰɟɧɬɪɚɰɢʁɚ ɨɛɚ ɛɢɨɦɚɪɤɟɪɚ ɭ ɭɪɢɧɭ ɨɞɪɟђɟɧɚ ʁɟ ɩɪɢɦɟɧɨɦ ɤɨɦɟɪɰɢʁɚɥɧɨɝ ELISA ɬɟɫɬɚ. ȿɤɫɩɪɟɫɢʁɚ KIM-1 ɭ ɬɭɦɨɪɫɤɨɦ ɬɤɢɜɭ ɨɞɪɟђɟɧɚ ʁɟ ɩɪɢɦɟɧɨɦ TIM-1/KIM-1/HAVCR ɚɧɬɢɬɟɥɚ. Ɋɟɡɭɥɬɚɬɢ ɨɜɟ ɫɬɭɞɢʁɟ ɫɭ ɩɨɤɚɡɚɥɢ ɞɚ ɨɞɪɟђɢɜɚʃɟ ɤɨɧɰɟɧɬɪɚɰɢʁɟ KIM-1 ɭ ɭɪɢɧɭ ɤɨɞ ɩɚɰɢʁɟɧɚɬɚ ɫɚ ɫɭɦʃɨɦ ɧɚ ɩɨɫɬɨʁɚʃɟ ɫɄȻ, ɩɪɟɞɫɬɚɜʂɚ ɫɟɧɡɢɬɢɜɚɧ ɢ ɫɩɟɰɢɮɢɱɚɧ ɬɟɫɬ ɡɚ ɩɪɟɨɩɟɪɚɬɢɜɧɭ ɞɢʁɚɝɧɨɡɭ ɛɨɥɟɫɬɢ ɢ ɞɚ ɡɧɚɱɚʁɧɨ ɤɨɪɟɥɢɪɚ ɫɚ ɫɬɚɞɢʁɭɦɨɦ ɢ ɝɪɚɞɭɫɨɦ ɬɭɦɨɪɚ. Ɉɞɪɟђɢɜɚʃɟ ɤɨɧɰɟɧɬɪɚɰɢʁɟ KIM-1 ɭ ɭɪɢɧɭ ɩɪɟɞɫɬɚʂɚ ɞɨɞɚɬɧɢ ɞɢʁɚɝɧɨɫɬɢɱɤɢ ɬɟɫɬ ɡɚ ɭɬɜɪђɢɜɚʃɟ ɩɪɢɪɨɞɟ ɦɚɥɢɯ ɬɭɦɨɪɫɤɢɯ ɩɪɨɦɟɧɚ ɩɪɨɦɟɪɚ ɞɨ 4 cm. ɉɨɪɟђɟʃɟɦ ɤɨɧɰɟɧɬɪɚɰɢʁɚ KIM-1 ɭ ɭɪɢɧɭ ɢɡɪɚɠɟɧɢɦ ɭ ɚɩɫɨɥɭɬɧɢɦ ɢ ɤɨɪɢɝɨɜɚɧɢɦ ɜɪɟɞɧɨɫɬɢɦɚ, ɧɢʁɟ ɩɨɤɚɡɚɧɚ ɫɬɚɬɢɫɬɢɱɤɢ ɡɧɚɱɚʁɧɚ ɪɚɡɥɢɤɚ ɭ ɞɢʁɚɝɧɨɫɬɢɱɤɨɦ ɩɨɬɟɧɰɢʁɚɥɭ. Ɍɤɢɜɧɚ ɟɤɫɩɪɟɫɢʁɚ KIM- 1 ɫɬɚɬɢɫɬɢɱɤɢ ɡɧɚɱɚʁɧɨ ɤɨɪɟɥɢɪɚ ɫɚ ɫɬɚɞɢʁɭɦɨɦ ɬɭɦɨɪɚ ɢ ɜɢɫɨɤɨ ɤɨɪɟɥɢɪɚ ɫɚ ɝɪɚɞɭɫɨɦ ɬɭɦɨɪɚ ɚɥɢ ɛɟɡ ɫɬɚɬɢɫɬɢɱɤɟ ɡɧɚɱɚʁɧɨɫɬɢ. Ʉɨɧɰɟɧɬɪɚɰɢʁɚ AQP-1 ɭ ɭɪɢɧɭ ʁɟ ɧɟɞɨɜɨʂɧɨ ɫɟɧɡɢɬɢɜɚɧ ɢ ɫɩɟɰɢɮɢɱɚɧ ɬɟɫɬ ɡɚ ɞɢʁɚɝɧɨɡɭ ɤɚɪɰɢɧɨɦɚ ɫɜɟɬɥɢɯ ʄɟɥɢʁɚ ɛɭɛɪɟɝɚ. Ⱦɚɬɭɦ ɩɪɢɯɜɚɬɚʃɚ ɬɟɦɟ ɨɞ ɫɬɪɚɧɟ ɇɇȼ 29.05.2013. Ⱦɚɬɭɦ ɨɞɛɪɚɧɟ - ȾɈ ɑɥɚɧɨɜɢ ɤɨɦɢɫɢʁɟ - ɄɈ ɉɪɨɮ. Ⱦɪ ɋɧɟɠɚɧɚ ɀɢɜɚɧɱɟɜɢʄ-ɋɢɦɨɧɨɜɢʄ ɉɪɨɮ. Ⱦɪ ɇɨɜɚɤ Ɇɢɥɨɜɢʄ ɉɪɨɮ. Ⱦɪ ɋɧɟɠɚɧɚ ɐɟɪɨɜɢʄ ɉɪɟɞɫɟɞɧɢɤ ɉɪɨɮ. Ⱦɪ ɋɧɟɠɚɧɚ ɀɢɜɚɧɱɟɜɢʄ ɋɢɦɨɧɨɜɢʄ ɑɥɚɧ ɉɪɨɮ. Ⱦɪ ɇɨɜɚɤ Ɇɢɥɨɜɢʄ ɑɥɚɧ ɉɪɨɮ. Ⱦɪ ɋɧɟɠɚɧɚ ɐɟɪɨɜɢʄ UNIVERSITY OF KRAGUJEVAC, FACULTY OF MEDICAL SCIENCES KEY WORDS DOCUMENTATION Accesion Number - ANO Identification number - INO Document type - DT Monographic publication Type of record – TR Textual material, printed Contens code - CC PhDThesis Author - AU MТrУКЧКMТУušФШvТć Menthor - MN DОУКЧ ЈОtrШvТć Title - TI Diagnostic value of kidney injury molecul -1 ( KIM-1) and aquaporins 1 ( AQP-1) in patients with clear renal cell carcinoma Language of text - LT Serbian Language of abstract - LA Serbian / English Country of publication - CP Serbia Locality of publication - LP Shumadia Municipality Publication year – PY Publicher-PB 2015. Authors reprint Publication place - PP 34000 Kragujevac, st.Svetozar Markovic 69 Physical description - PD Ɍhesis contains 130 pages, 7 chapters, 111 tables, 14 graphs and 251 citations Scietific field - SF Medicine Scientific discipline - SD Experimental and clinical internal medicine Subjest / Key words - SKW Urinary biomarker, KIM-1, AQP-1, diagnostic value, clear renal cell carcinoma UDC Holding data - HD Library of Faculty of Medicine, University of Kragujevac, Serbia Note - N Abstract - AB Renal cell carcinoma (RCC) represents approximately 3.8% of all malignancies in adults, increasing permanently over the past 30 years. The most common and also the most aggressive subtype of RCC is clear renal cell carcinoma (cRCC), often characterized by lack of early symptoms, signs and laboratory abnormalities. A reliable urine test for cRCC could have importance in the preoperative diagnosis of this tumor as an additional marker for the monitoring of response to therapy and for the post-treatment surveillance, as well. Recent studies have shown the increased expression of certain proteins in tumor tissue of cRCC. Based on the potential for urinary excretion of these up- regulated proteins, as well as the sensitivity and specificity for the diagnosis of cRCC, the kidney injury molecul 1 (KIM-1) and aquaporin 1 (AQP-1) have a special significance. The aim of this study was to investigate the potential of KIM-1 and AQP-1 for the diagnosis of cRCC, especially lesion diameter up to 4 cm, and the linkage of their concentration in urine and histological characteristics of the tumor. The study involved 41 patients (26 men, 15 women), who underwent the partial or radical nephrectomy and diagnosed cRCC. The control group consisted of 40 healthy subjects. The concentration of both biomarkers in the urine was determined by commercially available ELISA kits. Expression of KIM-1 in the tumor tissue is determined by applying the TIM-1/KIM-1/HAVCR antibody. Results of this study showed that the determination of the concentration of KIM-1 in the urine of patients with suspected cRCC is sensitive and specific test for the preoperative diagnosis of the disease and significantly correlated with tumor stage and grade. Determination of KIM-1 in urine represented a further diagnostic test to determine the nature of small lesion sizes up to 4 cm. By comparing the concentration of KIM-1 in urine expressed in absolute and corrected values, we did not show statistically significant difference in the diagnostic potential. Tissue expression of KIM-1 is significantly correlated with tumor stage and highly correlated with tumor grade but without statistical significance. The concentration of AQP-1 in urine was insufficiently sensitive and specific test for diagnosis of cRCC. Accepted by the Scientific Board on - ASB 29.05.2013. Defended on - DE Thesis defended Board - DB Prof. dr ЋЧОžКЧК ŽТvКЧčОvТć ЋТЦШЧШvТć Faculty of Medicine, University of Kragujevac, Kragujevac ЈrШП. Нr NШvКФ MТХШvТć Military Medical Academy, University of Defence, Belgrade Prof. dr ЋЧОžКЧК CОrШvТć Military Medical Academy, University of Defence, Belgrade Chairman Prof. dr ЋЧОžКЧК ŽТvКЧčОvТć ЋТЦШЧШvТć Member ЈrШП. Нr NШvКФ MТХШvТć Member Prof. dr ЋЧОžКЧКCОrШvТć ȻɂɈȽɊȺɎɋɄɂ ɉɈȾȺɐɂ ȺɍɌɈɊȺ ɂɦɟ ɢ ɩɪɟɡɢɦɟ Ɇɢɪʁɚɧɚ Ɇɢʁɭɲɤɨɜɢʄ Ⱦɚɬɭɦ ɢ ɦɟɫɬɨ ɪɨђɟʃɚ 8. ʁɭɥ 1970., ɑɚɱɚɤ, ɋɪɛɢʁɚ ɋɚɞɚɲʃɟ ɡɚɩɨɫɥɟʃɟ Ʌɟɤɚɪ ɫɭɛɫɩɟɰɢʁɚɥɢɫɬɚ ɭ Ʉɥɢɧɢɰɢ ɡɚ ɧɟɮɪɨɥɨɝɢʁɭ ȼɆȺ Ʉɨɧɬɚɤɬɢ Ȼɨɪɫɤɚ 82, 11 000 Ȼɟɨɝɪɚɞ, ɋɪɛɢʁɚ Ɍɟɥɟɮɨɧ: (011) 3593524 ȿɥɟɤɬɪɨɧɫɤɚ ɩɨɲɬɚ: mirjana.mijuskovic@gmail.com Ɉɫɧɨɜɧɟɫɬɭɞɢʁɟ Ɇɟɞɢɰɢɧɫɤɢ ɮɚɤɭɥɬɟɬ ɍɧɢɜɟɪɡɢɬɟɬɚ ɭ Ȼɟɨɝɪɚɞɭ, ɞɢɩɥɨɦɢɪɚɥɚ 1995. ɋɩɟɰɢʁɚɥɢɫɬɢɱɤɟ ɫɬɭɞɢʁɟ ɢɡ ɢɧɬɟɪɧɟ ɦɟɞɢɰɢɧɟ Ƚɪɭɩɚ ɢɧɬɟɪɧɢɯ ɤɥɢɧɢɤɚ ȼɨʁɧɨɦɟɞɢɰɢɧɫɤɟ ɚɤɚɞɟɦɢʁɟ, ɫɩɟɰɢʁɚɥɢɫɬɢɱɤɢ ɢɫɩɢɬ 2002. Ⱦɨɤɬɨɪɫɤɚ ɞɢɫɟɪɬɚɰɢʁɚ Ⱦɢʁɚɝɧɨɫɬɢɱɤɢ ɡɧɚɱɚʁ ɩɪɨɬɟɢɧɚ ɨɲɬɟʄɟʃɚ ɛɭɛɪɟɝɚ1 (KIM-1) ɢ ɚɤɜɚɩɨɪɢɧɚ 1 (AQP-1)ɤɨɞ ɛɨɥɟɫɧɢɤɚ ɤɨʁɢ ɛɨɥɭʁɭ ɨɞ ɤɚɪɰɢɧɨɦɚ ɫɜɟɬɥɢɯ ʄɟɥɢʁɚ ɛɭɛɪɟɝɚ Ɉɛɥɚɫɬɢ ɧɚɭɱɧɨɝ ɢɧɬɟɪɟɫɚ ɢ ɢɫɬɪɚɠɢɜɚʃɚ Ɉɧɤɨ-ɧɟɮɪɨɥɨɝɢʁɚ ɉɪɢɦɚɪɧɟ ɢ ɫɟɤɭɧɞɚɪɧɟ ɝɥɨɦɟɪɭɥɨɩɚɬɢʁɟ Ɍɪɚɧɫɩɥɚɧɬɚɰɢɨɧɚ ɧɟɮɪɨɥɨɝɢʁɚ Ʉɪɟɬɚʃɚ ɭ ɫɥɭɠɛɢ 2013. ɢ ɞɚʂɟ, ɢɧɬɟɪɧɢɫɬɚ-ɧɟɮɪɨɥɨɝ II ɨɞɟʂɟʃɚ Ʉɥɢɧɢɤɟ ɡɚ ɧɟɮɪɨɥɨɝɢʁɭ ȼɆȺ 2010–2013. ɢɧɬɟɪɧɢɫɬɚ-ɧɟɮɪɨɥɨɝ ɭ Ɉɞɟʂɟʃɭ ɡɚ ɯɟɦɨɞɢʁɚɥɢɡɭ Ʉɥɢɧɢɤɟ ɡɚ ɧɟɮɪɨɥɨɝɢʁɭ ȼɆȺ 2007-2010. ɢɧɬɟɪɧɢɫɬɚ-ɧɟɮɪɨɥɨɝ ɭ ɐɟɧɬɪɭ ɡɚ ɬɪɚɧɫɩɥɚɧɬɚɰɢʁɭ ɫɨɥɢɞɧɢɯ ɨɪɝɚɧɚ ȼɆȺ 2003-2005. ɥɟɤɚɪ ɫɩɟɰɢʁɚɥɢɫɬɚ ɢɧɬɟɪɧɟ ɦɟɞɢɰɢɧɟ I ɨɞɟʂɟʃɚ Ʉɥɢɧɢɤɟ ɡɚ ɧɟɮɪɨɥɨɝɢʁɭ ȼɆȺ 1998-2002. ɥɟɤɚɪ ɧɚ ɫɩɟɰɢʁɚɥɢɡɚɰɢʁɢ ɢɡ ɢɧɬɟɪɧɟ ɦɟɞɢɰɢɧɟ, Ƚɪɭɩɚ ɢɧɬɟɪɧɢɯ ɤɥɢɧɢɤɚ, ȼɆȺ ɑɥɚɧɫɬɜɚ ɢ ɩɨɡɢɰɢʁɟ ɍɞɪɭɠɟʃɟ ɧɟɮɪɨɥɨɝɚ ɋɪɛɢʁɟ ɇɟɮɪɨɥɨɲɤɚ ɫɟɤɰɢʁɚ ɋɪɩɫɤɨɝ ɥɟɤɚɪɫɤɨɝ ɞɪɭɲɬɜɚ ȿɜɪɨɩɫɤɨ ɭɞɪɭɠɟʃɟ ɡɚ ɧɟɮɪɨɥɨɝɢʁɭ, ɞɢʁɚɥɢɡɭ ɢ ɬɪɚɧɫɩɥɚɧɬɚɰɢʁɭ ȻɂȻɅɂɈȽɊȺɎɋɄɂ ɉɈȾȺɐɂ ȺɍɌɈɊȺ ɊȺȾɈȼɂ ɒɌȺɆɉȺɇɂ ɍ ɐȿɅɂɇɂ ɍ ȾɈɆȺȶɂɆ ɑȺɋɈɉɂɋɂɆȺ 1. 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KШЧРrОs ЧОПrШХШРК ЋrЛТУО, BОШРrКН, 11-14. oktobar 2012, apstrakt P 15. 8. TКНТć ЈТХčОvТć J, MТУušФШvТć M, ČuФТć Г, ЈТХčОvТć D, OЛrОЧčОvТć K, ЈОtrШvТć M, IРЧУКtШvТć LУ, TОrгТć B, KШvКčОvТć Z. Paratireoidektomija u bolesnice sa mekotkivnim kalcifikacijama – prikaz sХučКУК. KЧУТРК sКžОtКФК, 2. KШЧРrОs ЧОПrШХШРК ЋrЛТУО, BОШРrКН, 11-14. oktobar 2012, apstrakt S 3. 9. OЛrОЧčОvТć K, JШvКЧШvТć D, KШvКčОvТć Г, ЈОtrШvТć M, TОrгТć B, IРЧУКtШvТć LУ, ЈТХčОvТć D, ЈТХčОvТć TКНТć J, ЊКНШУОvТć M, VКvТć N, MКФsТć Đ, MТУušФШvТć M, ČuФТć Г. ЋКvrОЦОЧК tОrКpТУК ТНТШpКtsФО rОtrШpОrТtШЧОКХЧО ПТЛrШгО. KЧУТРК sКžОtКФК, 2. KШЧРrОs ЧОПrШХШРК ЋrЛТУО, BОШРrКН, 11- 14. oktobar 2012, apstrakt P 1. 10. ЈОtrШvТć M, JШvКЧШvТć D, IРЧУКtШvТć LУ, KШvКčОvТć Г, OЛrОЧčОvТć K, ЈТХčОvТć D, MТУušФШvТć M. ЊКЛНШЦТШХТгК ФКШ uгrШФ КФutЧО ЛuЛrОžЧО ТЧsuПТМТУОЧМТУО – ЧКšО ТsФustvШ. KЧУТРК sКžОtКФК, 2. Kongres nefrologa Srbije, Beograd, 11-14. oktobar 2012, apstrakt P 2. 11. KШvКčОvТć Г, VОХУКЧčТć LУ, ЊКНШУОvТć M, ЈКuЧТć Г, VКvТć N, MКФsТć Đ, OЛrОЧčОvТć K, TОrгТć B, ЈТХčОvТć TКНТć J, ЈТХčОvТć D, MТУušФШvТć M, ЈОtrШvТć M, ČuФТć Г, ЊКЛrОЧШvТć V, JШvКЧШvТć D, IРЧУКtШvТć LУ. OН КНОФvКtЧО ФК ШptТЦКХЧШУ НТУКХТгТ – prepreke i putokaгТ. KЧУТРК sКžОtКФК, 2. Kongres nefrologa Srbije, Beograd, 11-14. oktobar 2012, apstrakt P 30. 12. ЈТХčОvТć D, MКФsТć Đ, ЈКuЧТć Г, ЈОtrШvТć M, TОrгТć B, ЈТХčОvТć TКНТć J, OЛrОЧčОvТć K, MТУušФШvТć M, ЈОtrШvТć M, ČuФТć Г, KШvКčОvТć Г. CurОЧУО НТУКХТгКtК u prОНЧУТ trЛušЧТ гТН ФКШ ФКsЧК ФШЦpХТФКМТУК ФШН ЛШХОsЧТМО ЧК CAЈD prШРrКЦu ХОčОЧУК – prТФКг sХučКУК. KЧУТРК sКžОtКФК, 2. Kongres nefrologa Srbije, Beograd, 11-14. oktobar 2012, apstrakt S 30. 13. ЈТХčОvТć D,MКФsТć Đ, ЈКuЧТć Г, TОrгТć B, ЈОtrШvТć M, ЈТХčОvТć TКНТć J, MТУušФШvТć M, ЈОtrШvТć M, ČuФТć Г, KШvКčОvТć Г. MТФrШЛТШХШšФТ prШПТХ CAЈD pОrТtШЧТtТsК ФШН pКМТУОЧКtК ЧК СrШЧТčЧШЦ prШРrКЦu ХОčОЧУК pОrТtШЧОuЦsФШЦ НТУКХТгШЦ u ЧКšОЦ МОЧtru – pОtШРШНТšЧУК КЧКХТгК. KЧУТРК sКžОtКФК, 2. KШЧРrОs ЧОПrШХШРК ЋrЛТУО, BОШРrКН, 11-14. oktobar 2012, apstrakt S 36.