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 metaboličkogsindroma koji je povezan sa povećanim rizikom za nastanak kardiovaskularnih bolesti.Smatra se da hronična inflamacija ima bitnu ulogu u njegovoj patogenezi. Ženke suzaštićene od ishranom izazvanih metaboličkih poremećaja i hipertenzije ureproduktivnom periodu. Estrogen, koji utiče na normalno funkcionisanjekardiovaskularnog sistema, bi mogao doprinositi uočenim polno specifičnim razlikama unastanku simptoma metaboličkog sindroma. Proteinske komponente renin-angiotenzinsistema (RAS) imaju bitnu ulogu u nastanku inflamacije, hipertenzije i insulinskerezistencije i na njihovu ekspresiju utiče estradiol. Ova doktorska disertacija je za ciljimala 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) ikolektrina] 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 trajanjuod 9 nedelja predstavljali su animalni model metaboličkog sindroma korišćen u ovojstudiji. Radi ispitivanja efekata estradiola jedan deo ženki pacova je ovarijektomisan ipodeljen u tri grupe pri čemi je jedna grupa pored standardne laboratorijske hrane pilavodu, druga grupa je pila 10% rastvor fruktoze, a treća grupa je pored rasvora fruktozeprimala i supstitucionu terapiju estradiolom. Ishrana bogata fruktozom je uzrokovalapovećanje krvnog pritiska samo kod mužjaka pacova. Ovaj tip ishrane nije doveo dopromena u masi srca niti u odnosu masa srca/masa tela ni kod jednog pola, kao ni kodovarijektomisanih životinja što ukazuje da se hipertrofija srca nije razvila...

Fructose rich diet (FRD) represents an important factor in the development ofmetabolic syndrome. Metabolic syndrome is associated with increased risk forcardiovascular diseases occurrence and chronic inflammation has a major role in itspathogenesis. Females are protected from diet-induced metabolic disturbances andhypertension in their reproductive period. Estrogen, which influences the cardiovascularsystem, could contribute to the observed gender-specific differences in the onset ofmetabolic syndrome. Components of the renin-angiotensin system (RAS), the synthesisof which is mediated by estrogen, have an important role in the inflammatory processes,hypertension and insulin resistance. Almost all of the components of metabolic syndromeincrease the activity of RAS, which finally results in increased oxidative stress andinflammation. The aim of this doctoral dissertation was to investigate sex specific changesand role of estradiol in the expression of RAS components [angiotensin convertingenzyme (ACE), angiotensin converting enzyme 2 (ACE2), angiotensin receptor type 1(AT1R), angiotensin receptor type 2 (AT2R) and collectrin], as well as mediators ofinflammation and remodeling of heart tissue [nuclear faktor κB (NFκB), matrixmetalloproteinse-9 (MMP-9) and CXCL16 chemokine] in the animal model of metabolicsyndrome.Male and female rats, which consumed 10% fructose solution instead of water for9 weeks, represent an animal model of metabolic syndrome that was used in this study. Inorder to examine the effects of estradiol in the context of FRD, female rats wereovariectomized and divided in three groups: fed normal diet, fed FRD, and fed FRD andsubjected to estradiol replacement therapy. FRD increased blood pressure only in malerats. This diet regime didn't cause heart hypertrophy neither in intact males and females,nor in ovariectomized females...