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.
ABSTRACT
AIM: To investigate the effect of aminoguanidine (AG) on plasma and renal levels of angiogenesis Ⅱ (AngⅡ), and to identify the relationship of AGEs with AngⅡ in STZ-induced diabetic rats. METHODS: Wistar rats were randomly assigned to three groups. Diabetes was induced, rats were then received AG in treatment group. At the end of 12th week, urine albumin excretion rate (UAER) and calculate creatinine clearance (Ccr) were detected. Periodic acid-Schiff reagent was used to evaluate renal pathology. Plasma and renal AngⅡ were analyzed by radioimmunoassay and immunohistochemistry, respectively. RESULTS: AG treatment significantly prevented the increase in UAER (P<0.01), renal pathology (P<0.01), and level of renal AngⅡ (P<0.01). However, plasma concentration of AngⅡ was higher than that in diabetic rats without AG treatment (P<0.01). CONCLUSION: AG down-regulates renal Ang Ⅱ level, probably by reducing the formation of AGEs, which may be one of the renoprotective factors in diabetic nephropathy. More proofs are needed to identify the result that plasma AngⅡ concentration increases in DMA group.