Effects of Simvastatin on Expression of Activator Protein-1 in Renal Tissues of Diabetic Rats

Objective: To study the molecular mechanism of activator protein-1(AP-1) in renal tissues of diabetic rats,and to investigate the effects of simvastatin on AP-1 and its protection to kidney during the development of diabetic nephropathy(DN).Methods: SD male rats were randomly divided into three groups: normal control group(C),diabetic group(DM),and simvastatin treated group(DS).The expression of AP-1(c-jun mRNA)in renal tissues was measured with in situ hybridization.The expressions of macrophage inflammatory protein-1α(MIP-1α) and fibronectin(FN) were measured with Immuno-histochemstry method.The levels of triglyceride(TG),total cholesterol(TC),creatinine(Cr) and 24-hour urine protein excretion were measured with biochemistry methods.Results: The expressions of AP-1,MIP-1α and FN in glomeruli were increased in group DM and were inhibited by simvastatin treatment(P0.01).The levels of 24-hour urine protein,TG,TC and Cr in group DS were lower than those in group DM(P0.01).The renal histology changes were markedly relieved in group DS as compared with that in group DM.Conclusions: AP-1 plays an important role in the development of diabetic nephropathy.One of Reno-protective effects of simvastatin might be inhibition of AP-1 activity.