Uticaj ishrane bogate fruktozom na ekspresiju komponenti renin-angiotenzin sistema i inflamacije u tkivu srca pacova: polno specifične razlike

Abstract

Ishrana bogata fruktozom predstavlja bitan faktor u razvoju metaboličkog sindroma koji je povezan sa povećanim rizikom za nastanak kardiovaskularnih bolesti. Smatra se da hronična inflamacija ima bitnu ulogu u njegovoj patogenezi. Ženke su zaštićene od ishranom izazvanih metaboličkih poremećaja i hipertenzije u reproduktivnom periodu. Estrogen, koji utiče na normalno funkcionisanje kardiovaskularnog sistema, bi mogao doprinositi uočenim polno specifičnim razlikama u nastanku simptoma metaboličkog sindroma. Proteinske komponente renin-angiotenzin sistema (RAS) imaju bitnu ulogu u nastanku inflamacije, hipertenzije i insulinske rezistencije i na njihovu ekspresiju utiče estradiol. Ova doktorska disertacija je za cilj imala da ispita da li pol i estradiol doprinose promenama u ekspresiji komponenti RAS-a [angiotenzin konvertujućeg enzima (ACE), angiotenzin konvertujućeg enzima 2 (ACE2), angiotenzinskog receptora tipa 1 (AT1R), angiotenzinskog receptora tipa 2 (AT2R) i kolektrina] i medijatora inflamacije i remodelovanja tkiva srca [nuklearnog faktora κB (NFκB), matriks metaloproteinaze-9 (MMP-9) i liganda 16 iz familije hemokina CXC (CXCL16)] kod animalnog modela metaboličkog sindroma. Mužjaci i ženke pacova koji su pili 10% rastvor fruktoze umesto vode u trajanju od 9 nedelja predstavljali su animalni model metaboličkog sindroma korišćen u ovoj studiji. Radi ispitivanja efekata estradiola jedan deo ženki pacova je ovarijektomisan i podeljen u tri grupe pri čemi je jedna grupa pored standardne laboratorijske hrane pila vodu, druga grupa je pila 10% rastvor fruktoze, a treća grupa je pored rasvora fruktoze primala i supstitucionu terapiju estradiolom. Ishrana bogata fruktozom je uzrokovala povećanje krvnog pritiska samo kod mužjaka pacova. Ovaj tip ishrane nije doveo do promena u masi srca niti u odnosu masa srca/masa tela ni kod jednog pola, kao ni kod ovarijektomisanih životinja što ukazuje da se hipertrofija srca nije razvila...

Fructose rich diet (FRD) represents an important factor in the development of metabolic syndrome. Metabolic syndrome is associated with increased risk for cardiovascular diseases occurrence and chronic inflammation has a major role in its pathogenesis. Females are protected from diet-induced metabolic disturbances and hypertension in their reproductive period. Estrogen, which influences the cardiovascular system, could contribute to the observed gender-specific differences in the onset of metabolic syndrome. Components of the renin-angiotensin system (RAS), the synthesis of which is mediated by estrogen, have an important role in the inflammatory processes, hypertension and insulin resistance. Almost all of the components of metabolic syndrome increase the activity of RAS, which finally results in increased oxidative stress and inflammation. The aim of this doctoral dissertation was to investigate sex specific changes and role of estradiol in the expression of RAS components [angiotensin converting enzyme (ACE), angiotensin converting enzyme 2 (ACE2), angiotensin receptor type 1 (AT1R), angiotensin receptor type 2 (AT2R) and collectrin], as well as mediators of inflammation and remodeling of heart tissue [nuclear faktor κB (NFκB), matrix metalloproteinse-9 (MMP-9) and CXCL16 chemokine] in the animal model of metabolic syndrome. Male and female rats, which consumed 10% fructose solution instead of water for 9 weeks, represent an animal model of metabolic syndrome that was used in this study. In order to examine the effects of estradiol in the context of FRD, female rats were ovariectomized and divided in three groups: fed normal diet, fed FRD, and fed FRD and subjected to estradiol replacement therapy. FRD increased blood pressure only in male rats. This diet regime didn't cause heart hypertrophy neither in intact males and females, nor in ovariectomized females...