Effect of proteasome inhibitor MG132 on Smad7 expression in early diabetic nephropathy rat

Objective To observe the therapeutic effect of proteasome inhibitor MG132 on the early diabetic nephropathy rat and the expression of the Smad7 protein in kidney.Methods 45 healthy male Wistar rats were randomly divided into normal control group(NC group,n=10),diabetic models group(n=35).30 rats in diabetes models group were internalized the experiment after being induced by streptozotion,and divided into diabetic group(DC group,n=10),the high MG132 concentration group(MH group,n=10),the low MG132 concentration group(ML group,n=10).MH group and ML group received MG132 by intraperitoneal injection,meanwhile,NC group and DC group were treated by equal normal saline intraperitoneal injection daily.Half of rats in each group were sacrificed at 6 weeks and 8 weeks after treatment.Body weight(BW)of the rats were measured,and heart blood samples were taken to measure the fasting plasma glucose(FPG),as the ultrastructure of rat kidney changes were observed by electron microscopic and the expression level of Smad7 protein was detected by Western blot.Results (1)In each model group,the BW decreased obviously,but the FPG increased significantly compared with NC group(P0.01).While the BW of each model groups decreased at 8 weeks compared with 6 weeks(P0.05),and that in MH,ML group increased compared with DC group(P0.05);but there was no statistical difference among each model groups in FPG(P0.05).(2)Under the electron microscope,in all model groups glomerular basement membrane was thickened,foot process gap was widen or fusion and endothelial cells were edematous partly.These changes of MH group were milder compare with ML group,while that in DC group were the most apparent.But there were no statistical significances between 8 weeks and 6 weeks in each group.(3)Compared with NC group,the expression of Smad7 decreased in DC group(P0.01).After the rats were treated with MG132,there were statistical significances among MH and ML group(P0.05).With time,the differences between 6 weeks and 8 weeks were more obvious(P0.05).Conclusions The ubiquitin degradation of Smad7 increased in diabetic nephropathy.Proteasome inhibitor MG132 could inhibit Smad7 ubiquitin degradation and increase the expression of Smad7.