Effect of simvastatin on the expression of nephrin, podocin, and vascular endothelial growth factor (VEGF) in podocytes of diabetic rat.

Abstract

This study aims to investigate the effects and mechanisms of simvastatin on podocyte injuries in diabetic rats. Streptozotocin was used to induce diabetes in a rat model. Three groups were tested: normal control (NC) group, diabetes mellitus control (DM) group, and simvastatin (SVT) group. The serum creatinine, cholesterol, and urinary albumin excretion rate (UAER) were measured 4 to 8 weeks after administering either saline or the drug. Renal pathological changes were observed, and immunohistochemistry was performed to determine the expression of nephrin, podocin, and vascular endothelial growth factor (VEGF). Real-time PCR was performed to detect the mRNA expression levels of nephrin, podocin, and VEGF. Serum creatinine levels and the UAER were higher in the DM group than in the NC group (P < 0.01). The protein and mRNA expression levels of nephrin and podocin were lower in the DM group than in the NC group (P < 0.01); whereas, the expression of VEGF protein and mRNA was higher in the DM group than in the NC group (P < 0.01). Simvastatin (SVT) could reduce serum creatinine levels and the UAER, maintain the expression of nephrin and podocin, reduce the expression of VEGF, and improve the pathological changes of podocytes, which were much more pronounced at 8 weeks (P < 0.01). Simvastatin could maintain the distribution of nephrin and podocin in podocytes, inhibit VEGF expression, and thus improve podocyte injuries and protect kidney functions in diabetic rats.