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

11R-VIVIT inhibits the expression of urokinase-type plasminogen activator receptor in podocytes

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+11R-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+11R—VIVIT组(P<0.001);脂多糖+11R—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(PuPAR 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 （P0.001） and markedly reduced mRNA and protein expressions of uPAR （P uPAR mRNA 0.001; P uPAR =0.001）. Conclusion 11R-VIVIT can ameliorate proteinuria probably by decreasing the expression of uPAR in podocytes.