The Study Of The Protective Effects And Mechanism Of Losartan And Simvastatin On Kidney Of Diabetic Rats

Objective: To investigate the protective effects of angiotension II receptor antagonist Losartan and HMG-CoA reductase inhibitor Simvastatin on the kidneys of diabetic rats, and study their possible mechanisms.Methods: Rats prepared for the experiment were randomly divided into the following 5 groups: normal controlled rats (group C), streptozotocin diabetic rats (group D), and diabetic rats treated with Losartan (group D1), diabetic rats treated with Simvastatin (group D2), and diabetic rats treated with Losartan and Simvastatin (group D3). There are 9 or 10 experimental rats in each group. Fast blood glucose, serum cholesterol, triglyceride, blood urea nitrogen, creatinine and 24-hour urinary protein were observed after 8 weeks of treatment, while TGF- β1 and VEGF expression of kidneys was assessed by immunohistochemical staining.Results: Serum creatinine (P<0.01) , blood urea nitrogen (P< 0.05), 24-hour urinary protein (P<0.01) in diabetic rats treated withcombination of Losartan and Simvastatin were significantly lower than untreated diabetic rats. Serum creatinine and blood urea nitrogen concentrations in diabetic rats treated with either Losartan or Simvastatin were not significantly lower than untreated diabetic rats, however, 24-hour urinary protein was significantly reduced by either therapy. There was no significant difference in plasma lipids levels among different groups. Immunohistochemical staining showed that there was a significant increase in expressions of TGF-β1 and VEGF in diabetes rats compared with that of the normal controlled group. Expressions of TGF- β1 and VEGF were reduced by Losartan alone or in combination with Simvastatin. In the Simvastatin treatment group, only expression of TGF- β1, but not VEGF, was reduced compared to diabetic group.Conclusion: Losartan has renal protective effect on diabetes rats, partly through reducing TGF- β1 and VEGF expression. Simvastatin appears to confer renoprotective via effect on TGF- β1,independent of its lipid-lowering properties. Combination of both seems to confer further benefits in term of reducing albuminuria and serum blood urea nitrogen and creatinine concentration and helps to prevent renal damage of diabetic rats.