Mechanism of proteinuria prevention by combination of telmisartan and pioglitazone in diabetic nephropathy rats / 中华肾脏病杂志

ABSTRACT

Objective To study the combination effects of telmisartan and pioglitazone on the expression of heparanases (HPA) and podocin in the kidney of diabetic nephropathy (DN) rats and its possible mechanism. Methods DN model rats were established by intraperitoneal injection with STZ for 12 weeks. All the DN rats were randomly divided into telmisartan group (T group), pioglitazone group (P group), combination of telmisartan and pioglitazone group (L group), and DN group (D group). Healthy rats were chosen as healthy control group(N group). After garage with drugs for 12 weeks, 24-h urinary protein and serum biochemical indicators were examined. RT-PCR and immunohistochemistry methods were applied to detect the mRNA and protein expression of HPA and podocin. Results Compared with T group and P group, 24-h urinary protein of L group was markedly decreased(P<0.05). Compared with the N group, the level of fasting blood glucose, relative renal weight, BUN and Scr in other 4 groups were markedly increased (P<0.05). Compared with T group and P group, the Scr level and the expression of HPA mRNA and protein in L group was markedly decreased (P<0.05), and the protein and mRNA expression of podoein in L group was markedly increased (P<0.05). Conclusion Combination of telmisartan and pioglitazone can down-regulate the mRNA and protein expression of HPA of glomerular basement membrane and up-regulate the protein expression of podocin of podocyte in DN rats, which may ameliorate the proteinuria.