关键词：中药;糖尿病肾病;足细胞;凋亡;氧化应激;转分化;信号通路
中图分类号：R285.5 文献标识码：A 文章编号：1005-5304(2019)12-0136-05
DOI：10.3969/j.issn.1005-5304.2019.12.031 开放科学(资源服务)标识码(OSID)：
Research Progress in Molecular Mechanism of Diabetic NephropathyTreated by TCM Based on Podocyte Injury
GONG Caixia1， WANG Zhiqiang2
1. Shijiazhuang Ping'an Hospital， Shijiazhuang 050012， China; 2. The 980th Hospital of the Joint Logistics Support Force of Chinese People's Liberation Army，Shijiazhuang 050082， China
Abstract： Diabetic nephropathy is one of the main causes of end-stage renal diseases. As an integral part of glomerular filtration barrier， podocyte plays an important role in the development of diabetic nephropathy. Podocyte is one of the important targets of pathological mechanism and pharmacological research on the therapeutic drugs of diabetic nephropathy. This article discussed the molecular mechanism of the protective effects of TCM and its active components on podocyte injury in diabetic nephropathy from the aspects of anti-deletion， anti-apoptosis， anti-oxidative stress， anti-epithelial-mesenchymal transition and regulating signal pathway， and provided ideas and references for research on treatment of diabetic nephropathy with TCM.
Keywords： TCM; diabetic nephropathy; podocyte; apoptosis; oxidative stress; epithelial-mesenchymal transition; signal pathway
糖尿病腎病(diabetic nephropathy，DN)是糖尿病最常见的严重微血管并发症之一，也是导致终末期肾病的主要原因[1]。研究表明，足细胞损伤在DN的发生发展过程中起重要作用[2]。近年来，中医药治疗DN尤其是中药有效成分在防治DN方面取得了良好疗效。了解足细胞损伤的分子机制有助于探寻中药干预足细胞损伤的靶点，为中药防治DN提供新的思路和依据。本文就近年来中药及其有效成分对DN足细胞损伤保护的分子机制做一综述。
1 抗足细胞脱落
足细胞与肾小球基底膜(GBM)的紧密结合是维持肾小球滤过屏障结构完整性并防止尿蛋白排泄的病理学基础。研究显示，肾病患者尿沉渣中不但存在死亡足细胞，也存在正常足细胞[3]。此外，正常人尿液中也可培养出足细胞，整联蛋白α3、β1参与足细胞的黏附功能，是足细胞与GBM紧密结合的关键受体[4]，高糖可下调足细胞整联蛋白α3、β1表达，同时激活整联蛋白结合激酶(ILK)。Jim等[5]研究认为，糖尿病患者的足细胞标志性蛋白如synaptopodin、podocin和nephrin表达显著降低，可引起足细胞细胞骨架异常、黏附功能损伤，进而导致足细胞与GBM分离。Chen等[6]研究发现，黄芪甲苷可上调链脲佐菌素诱导DN大鼠足细胞整联蛋白α3、β1表达，抑制ILK表达，来保护足细胞。Gui等[7]的在体和体外实验显示，三七皂苷能通过上调足细胞整联蛋白α3、β1表达来改善糖尿病足细胞黏附功能异常。王旭焘等[8]研究显示，阿魏酸可显著上调糖尿病大鼠肾脏足细胞nephrin、podocin蛋白表达，减轻肾脏损伤。, http://www.100md.com(宫彩霞 王志强)