Effect of irbesartan on osteopontin expression and fibrosis in diabetic rat kidney / 中华肾脏病杂志

ABSTRACT

Objective To explore the effect of different doses of irbesartan on osteopontin expression and fibrosis in diabetic rat kidney. Methods Sixty-three g-week old male Wistar rat were randomly divided into control group (Ctrl group,n=7),diabetes group (DM group,n=14),30 mg·kg-1d-1 hydralazine administrated group (DM+Hyd group,n=12),25 mg·kg-1·d-1 irbesartan administrated group (DM+Irb25 group,n=10),50 mg·kg-1 ·d-1 irbesartan administrated group(DM+Irb50 group,n=9) and 200 mg·kg-1·d-1 irbesartan administrated group (DM+Irb200 group,n=11).Four weeks after modeling,rats were administered with the corresponding dose of irbesartan.After 12 weeks,urinary albumin excretion rate (UAER),endogenous creatinine clearance rate (Ccr) were measured; morphology and collagen deposition in rat kidney were observed by PAS and Masson staining respectively; Ang Ⅱ content in kidney was measured by ELISA; renal tissue TGF-β1 and OPN mRNA expression were detected by real-time PCR. Results UAER and Ccr in the intervention groups of irbesartan were significantly decreased compared with DM group (P＜0.05).UAER and Ccr in DM+Irb200 group were significantly lower than those in DM+Irb25 group and DM + Irb50 group (P＜0.05).Glomerular hypertrophy,mesangial matrix expansion,tubular lesions and deposition of collagen fiber were siginficant in diabetic rats compared with Ctrl,and prevented after administration with different doses of irbesartan.Ang Ⅱ protein level and TGF-β1,OPN mRNA expression in renal tissue of diabetic rats were significantly higher than those in Ctrl group.Ang Ⅱ,TGF-β1,and OPN mRNA expression was significantly reduced after administration with different doses of irbesartan,and with the increase of irbesartan,the above indicators were decreased P＜0.05).Renal local Ang Ⅱ level was positively correlated with OPN mRNA expression (r=0.74,P＜0.01). Conclusion Irbesartan reduces renal TGF-β1,OPN mRNA expression by decreasing kidney local Ang Ⅱ in dose-dependent manner,and eventually reduces tubulointerstitial fibrosis,which plays a role in kidney protection.