膜性肾病肾活检组织中TRPC6和podocalyxin表达改变及其意义

目的检测膜性肾病(membranous nephropathy,MN)患者肾活检组织中肾小球足细胞瞬时受体电位阳离子通道蛋白6(transient receptor potential cation channel 6,TRPC6)和podocalyxin的表达和分布,探讨足细胞蛋白TRPC6和podocalyxin在MN蛋白尿发生中的作用。方法采用常规组织病理以及免疫组化检查,并行免疫荧光双套色染色于激光共聚焦显微镜下观察TRPC6、podocalyxin在各组肾组织中表达及分布的改变,以计算机图像分析系统进行半定量分析。结果对照组肾组织podocalyxin沿肾小球毛细血管壁连续均匀分布,阳性荧光信号表达强,MN组表达减弱,且分布不均或节段性缺失,部分呈点状、短线状不连续分布,肾病综合征组较非肾病综合征组减弱更明显;TRPC6在对照组肾小球有一定的表达,沿肾小球基膜呈均匀连续线型分布,MN组TRPC6荧光强度有不同程度增强,且呈点状、团块状不均匀分布,肾病综合征组较非肾病综合征组更明显。结论 TRPC6和podocalyxin在正常肾组织沿肾小球基膜呈连续线状均匀分布;MN患者肾小球内TRPC6表达增加,podocalyxin表达减少,且分布形式亦发生变化,提示TRPC6和podocalyxin等足细胞相关蛋白表达改变及分布异常可能是MN蛋白尿发生的重要病理机制。

Expression changes of TRPC6 and podocalyxin in human membranous nephropathy

Purpose To study the expression changes of TRPC6 and podocalyxin in patients with membranous nephropathy(MN),and further to disclose the possible effects of TRPC6 and podocalyxin in the development of proteinuria in MN.Methods The expressions of the TRPC6 and podocalyxin in the glomeruli were examined by immunofluorescence and semi-quantitated by image analysis system.Results In control group,the distribution of podocalyxin showed a linear pattern along the glomerular basement membrane.In MN group,the staining of podocalyxin in glomeruli was weak and uneven,and lost of linear pattern with granular manner.In MN-A group,the glomerular expression of podocalyxin decreased significantly compared with those of MN-B group(P<0.05).The expression of TRPC6 in control group showed weak and linear uniformly distributed along the glomerular basement membrane.The expressions of TRPC6 in glomeruli were stronger in MN group than that of control group,and the former was lost of linear pattern with granular manner.In MN-A group,the glomerular expression of TRPC6 increased significantly compared with those of MN-B group(P<0.05).Conclusions The dramatic expression changes of podocalyxin and TRPC6 might contribute to the development of proteinuria in the patients of MN,suggesting that podocalyxin and TRPC6 may be the injury target in MN and imply the roles of podocalyxin and TRPC6 in the MN pathogenesis.