11R-VIVIT抑制脂多糖诱导的足细胞尿激酶型纤溶酶原激活剂受体的表达

摘要

目的 观察11R-VIVIT对脂多糖诱导的足细胞尿激酶型纤溶酶原激活剂受体(uPAR)表达的影响.方法 分别建立脂多糖诱导小鼠蛋白尿模型和脂多糖诱导足细胞损伤模型,两种模型均分为正常对照组、脂多糖组和脂多糖+ 11 R-VIVIT组.通过测量尿蛋白—尿肌酐比值观察各组小鼠尿蛋白的情况；通过免疫荧光激光共聚焦,RT-PCR及Western blot观察各组小鼠肾组织及足细胞uPAR基因及蛋白水平.结果 脂多糖组小鼠尿蛋白—尿肌酐比值高于正常对照组(P＜0.001)及脂多糖+11 R-VIVIT组(P.＜0.001)；脂多糖+ 11 R-VIVIT组的小鼠肾组织及足细胞的uPAR的荧光表达弱于脂多糖组,但与正常对照组相似；足细胞脂多糖+11R-VIVIT组的uPAR mRNA和uPAR蛋白表达均低于脂多糖组(PuuPAR mRNA＜0.001；PuPAR=0.001),但与正常对照组相类似(PuPAR mRNA=0.095；PuPAR=0.252).结论 11R-VIVIT可能通过抑制足细胞uPAR的表达、稳定和保护足细胞从而起到降蛋白尿的作用.%Objective To observe the effect of 11R-VIVIT on lipopolysaccharide (LPS)-induced expression of urokinase-type plasminogen activator receptor (uPAR) in podocytes.Methods A LPS-induced proteinuria mouse model and in vitro cultured podocytes treated with LPS were both divided into control group,LPS group and LPS+11 R-VIVIT group.The mRNA and protein expressions of uPAR in mouse kidney tissues and the podocytes were measured by real-time qPCR,laser scanning confocal microscopy and Western blotting.Results Compared with LPS group,LPS+11 R-VIVIT group showed a significantly lowered urine albumin/creatinine ratio (P＜0.001) and markedly reduced mRNA and protein expressions of uPAR (PuPAR mRNA＜0.001; PuPAR=0.001).Conclusion 11R-VIVIT can ameliorate proteinuria probably by decreasing the expression of uPAR in podocytes.