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氟伐他汀抑制高糖诱导足细胞发生上皮-间叶细胞转分化

来自:中国糖尿病资讯网  编辑:admin|点击数:|2011-08-25

  ·糖尿病基础研究·

  俞伟男 柏凤 谭若芸 杨俊伟

  基金项目:国家自然科学基金资助项目(30470800,30771010);科技部973重点项目(2006CB503909);江苏省“科教兴卫”工程医学领军人才项目

  作者单位:223002淮安,徐州医学院附属淮安医院,江苏省淮安市第二人民医院内分泌科(俞伟男、柏凤);江苏省糖尿病临床医学中心,南京医科大学第二附属医院肾脏病中心(谭若芸、杨俊伟)

  通讯作者:杨俊伟, E-mail: jwyang@njmu.edu.cn

  【摘要】 目的 探讨他汀类药物保护高糖诱导的糖尿病肾小球损伤的可能机制。 方法 给予25 mmol/L葡萄糖刺激的同时给予不同浓度的氟伐他汀处理分化后的足细胞36 h。采用蛋白免疫印迹法检测α-平滑肌肌动蛋白(α-SMA)、纤维粘连蛋白(FN)、CD2相关蛋白(CD2AP)和Wilms肿瘤1基因(WT-1)蛋白的表达;间接免疫荧光法检测α-SMA。 结果 低糖(5.6 mmol/L)条件下小鼠足细胞表达高水平的WT-1、CD2AP,基本不表达α-SMA 和FN;予25 mmol/L葡萄糖作用36 h后,足细胞中α-SMA和FN表达水平升高,同时WT-1和CD2AP表达水平降低。在高糖条件下给予不同浓度的氟伐他汀处理,结果表明氟伐他汀可部分逆转高糖的上述作用,且存在一定的剂量依赖性。 结论 氟伐他汀可在一定程度上抑制高糖诱导的足细胞发生向间叶细胞表型的转分化。

  【关键词】高糖;小鼠;足细胞;上皮细胞-间叶细胞转分化;氟伐他汀

  doi:10.3969/j.issn.1006-6187.2011.08.017

  Fluvastatin blockage of epithelial-mesenchymal transition induced by high glucose in mice podocyte cell line

  YU Wei-nan,BAI Feng,TAN Ruo-yun, et al. Division of Endocrinology,The 2nd Hospital of Huai′an,The Affilialted Huai′an Hospital, Xuzhou Medical University,Jiangsu Huai′an 223002, China

  Corresponding author: YANG Jun-wei, E-mail:jwyang@njmu.edu.cn

  【Abstract】 Objective To investigate the possible mechanism of fluvastatin inhibition of glomerular injury in diabetes mellitus mice. Methods Mice glomerular podocyte cells were co-incubrated with high glucose(25mM) and various dosages of fluvastatin for 36 hours. Then the cells were collected and the expressions of alpha-smooth muscle actin(α-SMA),fibronectin(FN),CD2-associated protein(CD2-AP) and Wilms\' tumor 1 gene (WT-1) were detected by Western blot and indirect immunofluorescence staining assays. Results Under low glucose(5.6mM) condition, there were high expressions of CD2AP and WT-1, and no expression of α-SMA and FN in mice podocyte cell. After 36 hours of treatment with high glucose(25mM), the expressions of α-SMA and FN in podocyte cells were significantly induced. When podoctyes were coincubated with various dosages of fluvastatin, the expressions of α-SMA and FN were downregulated in a dose-dependent manner. Meanwhile, the results of Western blot also showed that high glucose could downregulate the expressions of CD2AP and WT-1, while fluvastatin could partly reverse it in a dose-dependent manner. Conclusion Fluvastatin can partly inhibit glomerular injury under high glucose conditions through its blockage of podocyte EMT.

  【Key words】High Glucose; Mice; Podocytes; Epithelial-mesenchymal transition; Fluvastatin

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