雷公藤甲素对局灶节段性肾小球硬化足细胞损伤的调控机制

目的:通过观察雷公藤甲素(TP)对局灶节段性肾小球硬化(FSGS)大鼠及PAN致小鼠足细胞损伤模型中uPAR和TRPC6的表达影响,探讨TP对足细胞的保护作用.方法:将48只大鼠随机分为6组,Control组、Model组、TP-LD组、TP-MD组、TP-HD组和CSA组.除Control组外,其余各组均通过单侧肾切...

Regulatory mechanism of triptolide on podocyte injury in focal segmental glomerulosclerosis

Objective: To observe the effects of triptolide(TP) on the expression of urokinase type plasminogen activator receptor(uPAR) and transient receptor potential channel 6(TRPC6) in focal segmental glomerulosclerosis(FSGS) rats and PANinduced podocyte injury in mice, and to explore the protective effect of TP on podocytes. Methods: Forty-eight rats were randomly divided into 6 groups: Control group, Model group, TP-LD group, TP-MD group, TP-HD group and CSA group. Except for the Control group, the other groups were all treated by unilateral nephrectomy and repeated injection of doxorubicin in the tail vein to establish FSGS rat models. The drug group was treated with different concentrations of TP or CSA, and they were sacrificed after 8 weeks of intervention. The 24 h urine protein, serum creatinine and urea nitrogen in rats were deteded. The pathological changes of renal tissue were observed by HE staining, and the pathological changes of glomerular podocytes were observed by electron microscope. Western Blot detected the expression of uPAR and TRPC6 protein in kidney tissue. Cultured MPC5 were divided into Control group, PAN group, PAN+TP group, PAN+CSA group. The CCK-8 detected the effect of TP on the viability of podocytes induced by PAN, and Western Blot detected the protein levels of uPAR and TRPC6 in podocytes. Results: The 24 h urine protein, serum creatinine and urea nitrogen levels of the Model group were significantly higher than the Control group(P<0.01). The renal pathological examination showed focal segmental sclerosis, tubule expansion, epithelial cell shedding, and foot Process fusion. Western Blot examination found that compared with the Control group, the expression of Podocin in the Model group decreased, and the expression of TRPC6 and uPAR increased significantly(P<0.01). After TP intervention, rat urine protein, serum creatinine, urea nitrogen and kidney pathology were significantly improved, Podocin expression in renal tissue increased, and TRPC6 and uPAR expression decreased. As the concentration of TP increases, the protective effect of podocytes gradually increased, and the effect of high concentrations of TP was basically similar to CSA. Cell experiments further confirmed that MPC5 treated with PAN for 48 h, the expression of Podocin decreased significantly, and the expression of TRPC6 and uPAR increased TP treatment can effectively reverse the above changes. Conclusion: TP protects podocytes, reduces proteinuria, and improves FSGS by downregulating TRPC6 and uPAR.