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浙江大学学报(医学版)  2016, Vol. 45 Issue (2): 214-218    DOI: 10.3785/j.issn.1008-9292.2016.03.16
综述     
足细胞功能紊乱与微小病变性肾病
柳珊珊, 陈江华
浙江大学医学院附属第一医院肾脏病中心, 浙江 杭州 310003
New insight in pathogenesis of podocyte disfunction in minimal change disease
LIU Shanshan, CHEN Jianghua
Kidney Disease Center, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China
全文: PDF(961 KB)  
摘要: 

微小病变性肾病(MCD)是肾病综合征常见的病理类型之一,其病理主要表现为肾小球脏层上皮细胞足突广泛融合。目前越来越多的研究表明,足细胞损伤是MCD蛋白尿产生的关键环节。在MCD小鼠模型及人肾组织中均发现,足细胞裂隙膜蛋白nephrin、podocin和骨架蛋白synaptopodin的表达下调,且蛋白尿的多少与其表达下降程度相关;synaptopodin表达越多,患者对激素治疗反应越好。近年来,关于MCD足细胞损伤的焦点集中于足细胞来源的两种蛋白:CD80和血管生成素样蛋白4。来自外界的微生物或抗原作用于足细胞,通过激活κB基因序列致CD80过表达,进而破坏足细胞骨架蛋白,改变肾小球滤过率,引起蛋白尿;过表达的血管生成素样蛋白4可破坏肾小球基底膜电荷屏障,导致足突融合,诱发MCD。但有关诱发CD80和血管生成素样蛋白4持续过表达的关键因素以及两者与肾小球基底膜之间相互作用的具体致病过程并不明确,有待更深入的研究证实。基于MCD足细胞损伤机制的研究,NF-κB抑制剂和唾液酸化治疗措施在不久的将来也许可以作为MCD的一种新型的非免疫治疗方案。

关键词 足细胞肾病,脂性/病理学抗原,CD80血管生成素类蛋白尿综述    
Abstract

Minimal change disease (MCD) is a common pathological type of nephrotic syndrome. Its main histology is the fusion of podocyte foot process. The pathogenesis of MCD is not clear, but previously it was thought to be related to immune mechanism. In recent years more studies show that podocyte injury is the key link in the pathogenesis of MCD. In MCD mouse model and human kidney tissues, the expressions of podocyte slit membrane protein-nephrin and podocin, skeleton protein-synaptopodin are decreased, and the expression of synaptopodin is correlated with the response to hormone therapy. In addition, newest studies focused on another two potocyte associated proteins, CD80 and Angiopoietin-like-4. CD80, a T cell stimulating molecule, is expressed in potocyte. Kappa B gene sequences can be activated by external microbes, antigens through acting potocytes, which can induce the upregulation of CD80 expression, cytoskeletal protein damage and the glomerular filtration rate changes, resulting in proteinuria. Angiopoietin-like-4 can be expressed in normal potocytes, but over-expression of angiopoietin-like-4 may injure the GBM charge barrier and induce the foot process fusion, leading to MCD. However, further studies on the factors inducing CD80 and Angiopoietin-like-4 expression, and the interaction between glomerular basement membrane and the two proteins are needed. Based on the mechanism of MCD, NF-kappa B inhibitors and sialylation therapy would be a novel non-immune therapy for MCD.

Key wordsPodocytes    Nephrosis, lipoid/pathology    Antigens, CD80    Angiopoietins    Proteinuria    Review
收稿日期: 2015-08-15     
CLC:  R57  
基金资助:

国家自然科学基金(2011BAI60B07,2012CB517603)

通讯作者: 陈江华(1958-),男,硕士,教授,主任医师,博士生导师,从事肾脏病学、肾移植研究;E-mail:chenjianghua@zju.edu.cn     E-mail: chenjianghua@zju.edu.cn
作者简介: 柳珊珊(1990-),女,硕士研究生,从事肾病综合征治疗研究;E-mail:lsjnlss@163.com
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引用本文:

柳珊珊 等. 足细胞功能紊乱与微小病变性肾病[J]. 浙江大学学报(医学版), 2016, 45(2): 214-218.
LIU Shanshan, CHEN Jianghua. New insight in pathogenesis of podocyte disfunction in minimal change disease. Journal of ZheJiang University(Medical Science), 2016, 45(2): 214-218.

链接本文:

http://www.zjujournals.com/xueshu/med/CN/10.3785/j.issn.1008-9292.2016.03.16      或      http://www.zjujournals.com/xueshu/med/CN/Y2016/V45/I2/214

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