Antifibrotic Effects Of Benazepril In Rats With UUO And Its Mechanism

Abstract :Objective: To study the effect and mechanisms of benazepril on renal interstitial fibrosis induced by unilateral ureteral obstruction(UUO) in rats. Methods: The 36 SD rats were randomly divided into sham operation group, Model group and Benazepril group, 12 in each group. Model group and Benazepril rats were anesthetized, fixed, ligating the left ureter. Sham operation group, only free on the left ureter, and not to be obstructed. After synchronous intervention for 14 days, Abdominal aortic blood was collected, mensurated hemorrheologic indexes and serum BUN, creatinine. Left kidney was taken, HE staining and Masson staining observed renal interstitial changes; The expression of Collagen-I in kidney tissue was detected by the immunohistochemical method; ELISA method was used to detect the expression level of Collagen-I protein, AngII protein, TGF-β1 protein in kidney tissue; RT-PCR determine the expression changes of TGF-β1mRNA and Periostin mRNA in renal tissue. Results: (1) Renal function: Compared with model group, benazepril reduce the serum concentration of SCr and BUN of unilateral obstruction in rats significantly (P < 0.05). (2) HE staining: Compared with sham operation group, renal tubule was significantly expanded wider, showing interstitial inflammatory cell infiltration, significant degree of renal interstitial fibrosis in the model group rats,Compared with the model group, benazepril group inflammatory cells and the level of renal interstitial fibrosis were obviously decreased, no significant fibrosis. (3) Masson staining: the sham groups, Masson staining showed that collagen are mainly located in renal glomerular basement membrane, Bowman capsule, mesangial area and around the capillaries between renal tubulesin. Compared with the sham groups, in the Model rats, green collagen significantly increased, the width of renal interstitial broadened, tubular epithelial cell atrophy, luminal expanded, collagen fibrosis, renal interstitial fibrosis was significant. Compared with the model group, the extent of interstitial widening and degree of collagen deposition in interstitium was reduced significant- ly in benazepril group. (4) Changes in blood rheology: Compared with model group, benazepril could significantly reduce whole blood viscosity(WBV), plasma viscosity (PV),hematocrit(Hct), etc. (P < 0.05). (5) Immunohistochemistry results suggest that collagen type I: Compared with model group, collagen type I was decreased significantly in the rats of benazepril group (P < 0.05). (6) ELISA: compared with sham group, the expression of TGF-β1, Periostin, AngII, that in the interstitium of model group increased (P < 0.05), compared with model group, benazepril group were decreased significantly (P < 0.05), (7) RT-PCR: compared with the sham group, the expression of Periostin mRNA, were significantly increased about 85.37%, (P < 0.05), compared with model group, benazepril group were reduced significantly (P < 0.05),compared with the sham group, the expression of TGF-β1mRNA were increased significantly (P < 0.05), compared with model group, benazepril group were reduced significantly (P < 0.05). Conclusion: Benazepril may reduce the level of hemorheology indices to improve rat renal interstitial fibrosis and delay the process of renal interstitial fibrosis; Benazepril could reduce the expression of Periostin to improve the renal interstitial fibrosis by inhibiting Signal Transduction of AngII-TGF-β1.