Effect of unilateral ureteral obstruction and anti-angiotensin II treatment on renal tubule cell apoptosis and interstitial fibrosis in rats [Učinak jednostrane opstrukcije uretera i primjene anti-angiotenzina II apoptozu i intersticijalnu fibrozu bubrežnih tubularnih stanica u štakore]

Radović, Nikola and Aralica, Gorana and Galešić Ljubanović, Danica and Jeleč, Vjekoslav and Kontek, Mladen (2014) Effect of unilateral ureteral obstruction and anti-angiotensin II treatment on renal tubule cell apoptosis and interstitial fibrosis in rats [Učinak jednostrane opstrukcije uretera i primjene anti-angiotenzina II apoptozu i intersticijalnu fibrozu bubrežnih tubularnih stanica u štakore]. Collegium Antropologicum, 38 (2). pp. 583-588. ISSN 0350-6134

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Abstract

Unilateral ureteral obstruction (UUO) results in a number of pathophysiological and morphological changes in the renal parenchyma, including interstitial inflammation and fibrosis, apoptotic changes of tubular and interstitial cells. Recent studies have indicated an association between renin-angiotensin system and apoptotic alterations in the kidney after unilateral obstructive nephropathy. In this study, the effect of ACE inhibitors and AT1 receptor antagonists on tubular cell apoptosis and interstitial fibrosis in obstructive nephropathy after UUO in rats was investigated. The study was conducted on Wistar rats with unilaterally ligated ureter and sham operated animals (control group). The rats with UUO were treated with ACE inhibitor (cilazapril) or AT1 receptor antagonists (losartan) and control group was treated with H2O. Sham-operated animals were treated in the same way. Tubular and interstitial cell apoptosis was detected morphologically by hematoxylin and eosin (HE) staining and terminal deoxynucleotidyl transferase-mediated nick end-labeling (TUNEL). The area of intersitial fibrosis was determined using computer-assisted image processing after Gomory silver impregnation of paraffin sections. All experimental animal groups with unilateral ureter ligation showed a significantly increased number of apoptotic tubular and interstitial cells in the obstructed kidney compared with the contralateral, unobstructed kidney. Histomorphometric analysis of renal interstitial fibrotic changes in the groups of rats treated with losartan or water showed a statistically significant difference (p < 0.05) between the operated and sham--operated animals. In conclusion, following UUO there is a significantly increased number of apoptotic tubular cells and interstitial fibrosis in the ipsilateral kidney compared with the contralateral kidney. ACE inhibitors and AT1 receptor antagonists could not decrease the extent of renal cells apoptosis and interstitial fibrosis after UUO.

Abstract in Croatian

Rezultat jednostrane opstrukcije uretera (JOU) je gubitak parenhima u bubregu zbog atrofije kanalića, upalnih i fibroznih promjena u intersticiju i apoptoze stanica bubrežnih kanalića i intersticija. Dokazana je povezanost sustava renin-angiotenzin i apoptotskih promjena u bubregu nakon jednostrane opstrukcijske nefropatije. U ovoj studiji je istraživan učinak inhibitora ACE i antagonista receptora AT1 na apoptozu stanica tubula i na intersticijsku fibrozu kod opstrukcijske nefropatije nakon JOU u štakora. Istraživanje je provedeno na štakorima soja Wistar kojima je jednostrano podvezan ureter ili su bili lažno operirani (kontrola). Životinje s podvezanim ureterom obrađene su inhibitorima ACE (cilazapril) ili antagonistima receptora AT1 (lozartan), a kontrolna skupina životinja obrađena je s H2O. Lažno operirane životinje obrađene su na isti način. Apoptoza stanica u kanalićima i intersticiju je morfološki analizirana nakon bojenja hemalaun eozinom (HE) i bojanjem terminalne deoksinukleotidil transferaze na 3, – OH krajevima DNA (TUNEL). Površinu intersticijske fibroze na parafinskim prerezima odredili smo pomoću računalne obrade slike nakon impregnacije uzoraka srebrom po Gomoriu. U svim eksperimentalnim skupinama životinja s podvezanim ureterom značajno je povećan broj apoptotskih stanica u kanalićima bubrega u odnosu na suprotni, neopstruirani bubreg. Histomorfometrijska analiza fibroznih promjena intersticija bubrega u skupinama životinja obrađenih lozartanom ili vodom, pokazala je statistički značajnu razliku (p<0,05) između operiranih i lažno operiranih životinja. Nakon podvezanja jednog uretera dolazi do značajno povećanog broja apoptotskih stanica u kanalićima te fibroze istostranog bubrega u odnosu na suprotni bubreg. Inhibitori ACE i antagonisti receptora AT1 ne mogu smanjiti oštećenja stanica bubrega koja su nastala u tijeku JOU.

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