Protective Effect of Triptolide on Renal Tubulointerstitial Injury of Type 2 Diabetic Rats

Objective: To observe the effect of triptolide on the expression of BMP-7,CTGF and TGF-β1 in renal tubulointerstitium of type 2 diabetic rats,and explore the mechanism of its protective role.Methods: Wistar rats were randomly divided into three groups: control group(NC),diabetic model(DM) group and triptolide-treated diabetic(DT) group.Type 2 diabetic mellitus(T2DM) models in DM and DT groups were induced by feeding high fat-sugar diet for 8 weeks and given a low dose of STZ(30 mg.kg-1).After administration of triptolide for 8 weeks,blood pressure,blood glucose,urinary albumin(UAL) and Ccr,and renal morphological changes were observed.The protein expression of BMP-7,CTGF and TGF-β1 was detected by using immunohistochemistry and Western blot.The mRNA expression of BMP-7,CTGF,and TGF-β1 was assayed by using quantitative real-time PCR.Results: Compared to NC,UAL,FBG and KW/BW were increased significantly in DM group(P0.05,0.01).The expression of BMP-7 mRNA and protein was down-regulated in renal tubulointerstitium,and CTGF and TGF-β1 mRNA and protein was up-regulated significantly(P0.01).Correlation analysis showed that there was a negative correlation between UAL and BMP-7 mRNA(P0.01) and a positive correlation between UAL and CTGF,TGF-β1 mRNA. The number of ED-1 positive cells was correlated with the expression of TGF-β1 mRNA in renal interstitium.mRNA expression of TGF-β1 was correlated positively with CTGF,and negatively with BMP-7(P0.01).The ratio of atrophic renal tubule and interstitium fibrosis was correlated positively with CTGF,TGF-β1,and negatively with BMP-7(P0.05).Eight weeks later,UAL was decreased in DT group.Triptolide treatment alleviated the damage of renal tubulointerstitium.Meanwhile,the expression of BMP-7 was up-regulated remarkably in renal tubulointerstitium,and that of CTGF and TGF-β1 down-regulated remarkably(P0.05).Conclusion: Triptolide played an apparent role against renal tubulointerstitial injury of T2DM rats by,at least partly,down-regulating CTGF and TGF-β1 expression and up-regulating BMP-7 expression.