Effect Of Simvastatin On Expression Of CTGF And-catenin In Renal Tubulointerstitium Of Rats With Diabetic Nephropathy

Objective:To investigate the effect of simvastatin on the expression of connective tissue growthfactor (CTGF) and β-catenin in the renal tubulointerstitium of rats with streptozocin (STZ)-induced diabetic nephropathy.Methods:Wistar rats were intraperitoneal injected with STZ(60mg/kg) for the preparation of diabetic model. After4weeks, the rats with urinary protein>30mg/d were regarded as the model of diabetic nephropathy(n=20), and were randomly divided into diabetic nephropathy (DN group, n=10)and simvastatin group(DS group,n=10). Then ten healthy rats were selected randomly as control group(N group,n=10). DS group rats were treated with simvastatin group and DN group rats were given equal saline water. All the rats received daily gavages for12weeks. The following parameters were measured after4weeks,8weeks and12weeks in each groups respectively, blood glucose(Glu), body weight and the24h urinary protein; after12weeks serum creatinine(Scr), urea nitrogen(BUN) and triglyceride(TC) were measured; The renal pathological changes were detected under light microscope. The expression levels of CTGF and β-catenin in the renal tubulointerstitium were assessed by immunohistochemistry method. The expressions of CTGF mRNA and β-catenin mRNA in renal tissue were determined by Real—time quantitative PCR.Result:After8,12w, the24h urinary protein of DN group were respectively higher than those of the N group(P<0.05), while DS group lower than those in DN group(P<0.05). After12w, Scr and BUN of DN group were higher than those in N group(P<0.05), while DS group lower than those in DN group(P<0.05). There was no significant difference in TC level among all three groups(P<0.05). Pathological results:12weeks, the renal tissue of DN group mesangial cell proliferation, tubular also a remarkable expansion of the epithelial cell edema, glycogen vacuoles increased, tubular basement membrane is irregular increase thick; DS group renal tissue of mesangial cells and mesangial matrix proliferation reduced, a small number of tubular dilatation and edema. The expression levels of CTGF and β-catenin in the renal tubulointerstitium of the DN group were higher than those of N group(P<0.05); The expression levels of CTGF and β-catenin in the renal tubulointerstitium of the DS group were lower than those of DN group(P<0.05), while higher than those in N group (P<0.05). The expressions of CTGF and β-catenin mRNA of the DN group were higher than those of N group(P<0.05), while DS group were lower than those in DN group (P<0.05). Conclusion:Simvastatin could decrease24h protein urinary, protect the renal function, reduce the expression levels of CTGF and β-catenin of the DN rats renal tubulointerstitium. These findings suggest that simvastatin could delay the tubulointerstitial fibrosis, may be improbably through the regulation of CTGF and wnt/β-catenin signaling pathway to paly its protective effect.