Uticaj darbepoetina alfa na broj glomerula novorođenih miševa sa intrauterusnom restrikcijom rasta

Abstract

Intrauterusna restrikcija rasta (IUGR) se odnosi na stanje u kojem fetus nije u mogućnosti da ostvari svoj genetski potencijal za rast. IUGR je ozbiljan klinički problem i nedavno je povezan sa bolestima odraslog doba kao što su hipertenzija, insulin nezavistan diabetes melitus, dislipidemije i ishemijske bolesti srca. Eritropoetin je glavni regulator proliferacije i diferencijacije eritroidnih progenitorskih ćelija zahvaljujući svojoj antiapoptotičkoj aktivnosti. Cilj istraživanja je bio da se ispita uticaj IUGR na bubrege, kao i uticaj eritropotina na bubrege sa IUGR. Eksperimentalna studija je sprovedena u gajilištu Pasterovog zavoda u Novom Sadu na 60 miševa rase NMRI. IUGR je izazivana aplikacijom deksametazona gravidnim ženkama. Po rođenju su mladunci bili podeljeni u sedam grupa. Mladuncima je u 1. i 7. danu života davan darbepoetin alfa (DA) u dozama od 1, 4 i 10μg/kg. Dve grupe su predstavljale potomke majki koje su tokom trudnoće dobile DA. Nakon 4 nedelje su uzimani uzorci bubrega i vršena je morfološka i stereološka analiza glomerula. Aplikacija deksametazona (100 μg/kg) trudnim mišicama dovodi do potomstva sa IUGR. Primena DA kod novorođenih miševa sa IUGR dovodi do bržeg porasta telesne mase u prvih 7 dana života („catch-up― rasta). Miševi rođeni sa IUGR imaju manju površinu glomerula bubrega. Primena DA nakon rođenja i u 7. danu života (4 i 10 μg/kg) kod novorođenih miševa sa IUGR dovodi do hipertrofije glomerula bubrega. IUGR nema uticaja na broj glomerula bubrega miševa. Primena DA nema uticaja na broj glomerula bubrega miševa. Miševi rođeni sa IUGR imaju manju debljinu korteksa bubrega. Primena DA (4 i 10 μg/kg) kod miševa rođenih sa IUGR dovodi do povećanja debljine korteksa bubrega. Davanje DA kod IUGR značajno povećava površinu glomerula i debljinu korteksa bubrega.

Intrauterine growth restriction (IUGR) refers to a condition in which a foetus is not able to achieve its genetic potential for growth. IUGR is a serious clinical problem, and has recently been linked with diseases of adulthood, such as hypertension, insulin-independent diabetes mellitus, dyslipidemia, and ischemic heart disease. Erythropoietin is the major regulator of proliferation and differentiation of erythroid progenitor cells, thanks to its anti-apoptotic activities. The aim of this study was to investigate the effect of IUGR on the kidneys, and the impact of erythropoietin on the kidneys with IUGR. The experimental study was conducted in Pasteur Institute of Novi Sad on 60 mice of NMRI race. IUGR has been imposed with the application of dexamethasone to pregnant females. After birth, the pups were divided into seven groups. DA was administered to the pups on the 1st and 7th day of life (dose 1, 4 and 10 μg/kg). Two groups represented the offspring of the mothers who during pregnancy received DA. After 4 weeks, kidney samples were taken and morphological and stereological analysis of the glomeruli was performed. The application of dexamethasone (100 μg/kg) to pregnant mice leads to their offspring with IUGR. Application of DA to newborn mice with IUGR leads to faster weight gain in the first 7 days of life ("catch-up" growth). Mice born with IUGR have a reduced glomerular surface. Application of DA after birth and on the 7th day of life (4 and 10 μg/kg) in mice with IUGR leads to hypertrophy of the kidney glomeruli. IUGR has no effect on the number of kidney glomeruli. Application of DA has no effect on the number of kidney glomeruli. Mice born with IUGR have a reduced cortical thickness. Application of DA (4 and 10 μg/kg) in mice born with IUGR leads to increased thickness of the kidney cortex. Application of DA to mice with IUGR significantly increases the surface area of the kidney glomeruli and cortical thickness.