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肾脏病与透析肾移植杂志 ›› 2017, Vol. 26 ›› Issue (1): 37-43.DOI: 10.3969/cndt.j.issn.1006-298X.2017.01.007

• 论文 • 上一篇    下一篇

线粒体分裂相关蛋白高表达参与阿霉素大鼠肾病模型蛋白尿的发生

  

  • 出版日期:2017-02-28 发布日期:2017-02-21

Mitochondrial fission proteins are involved in proteinuria in adriamycininduced rat nephropathy

  • Online:2017-02-28 Published:2017-02-21

摘要:

目的:探讨肾小球线粒体动力相关蛋白1(Drp1)、PDrp1(Ser616)和线粒体分裂蛋白1(Fis1)表达与足细胞损伤及蛋白尿发生的关系。
方法:建立阿霉素大鼠肾病模型,用免疫组化和western blot检测肾小球和肾皮质Drp1、PDrp1(Ser616)及Fis1的表达,分析上述蛋白表达与蛋白尿及足细胞线粒体形态的相关性。在小鼠足细胞系MPC5过表达Drp1,分析对凋亡和线粒体形态的影响。
结果:肾小球和肾皮质Drp1在阿霉素大鼠肾病模型4周和6周时表达增强,肾小球PDrp1(Ser616)在6周时表达增强,肾小球Fis1在2周和6周时增强。肾小球和肾皮质Drp1、肾小球PDrp1(Ser616)和Fis1表达与24h尿蛋白正相关。肾小球Drp1表达量与足细胞线粒体胞浆密度和线粒体细胞密度呈负相关。肾小球PDrp1(Ser616)与足细胞线粒体最大长宽比呈负相关。肾小球Fis1与足细胞线粒体面积和周长呈负相关。过表达Drp1致小鼠足细胞凋亡显著增多,线粒体片段化。
结论:肾小球Drp1、PDrp1(Ser616)与Fis1高表达参与阿霉素大鼠肾病模型蛋白尿的发生,Drp1高表达致线粒体片段化和足细胞凋亡。

关键词: 蛋白尿, 足细胞, 线粒体分裂, 线粒体动力相关蛋白1, 线粒体分裂蛋白1

Abstract:

Objective:To investigate the glomerular expression of Drp1, PDrp1 (Ser616) and Fis1 in adriamycin (ADR) induced nephropathy rats and their relationship with podocyte injury.
Methodology:ADR rat nephropathy was established. Glomerular expressions of Drp1, PDrp1 (Ser616) and Fis1 were investigated by immunohistochemistry. Renal cortical expressions of Drp1 and Fis1 were evaluated by western blot. Correlation analysis was performed to analyze the correlations between mitochondrial fission proteins, proteinuria and mitochondrial morphology. Drp1 overexpression was performed on mouse podocyte cell line, mitochondrial morphology and apoptosis were evaluated.
Results:Glomerular expression of Drp1 increased at 4 and 6 weeks. Glomerular PDrp1 (Ser616) increased at 6 weeks by immunohistochemistry. Glomerular Fis1 increased at 2 and 6 weeks by immunohistochemistry. Glomerular expressions of Drp1, PDrp1 (Ser616) and Fis1 were negatively correlated with 24hour proteinuria positively. Glomerular expression of Drp1 was negatively correlated with mitochondria density in podocytes. Glomerular expression of PDrp1 (Ser616) was negatively correlated with mitochondria aspect ratio, and glomerular Fis1 was correlated with mitochondria area and circumference negatively. Drp1 overexpression led to podocyte apoptosis and mitochondrial fragmentation in MPC5.
Conclusion:Overexpressions of Drp1, PDrp1 (Ser616) and Fis1 participated in ADR nephropathy. Overexpression of Drp1 led to mitochondrial fragmentation and podocyte apoptosis.