罗格列酮阻断醛固酮诱导的肾小球系膜细胞增殖
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江苏省自然科学基金资助(BK2007259),江苏省"科教兴卫"工程医学重点人才基金资助(RC2007015)


Peroxisome proliferator-activated receptor-γ agonist inhibited aldosterone-induced mesangial cell proliferation
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    摘要:

    目的:①探讨氧化应激在醛固酮(ALDO)诱导的肾小球系膜细胞增殖中的作用;②探讨过氧化物酶体增殖物活化受体-酌(PPAR-酌)激动剂对醛固酮诱导的肾小球系膜细胞增殖的抑制作用-方法:体外培养小鼠肾小球系膜细胞,应用3H-胸腺嘧啶(3H-TdR)掺入法-细胞计数及流式细胞术测定系膜细胞增殖和细胞周期的变化;应用Western blot检测细胞周期素cyclin D和cyclin A表达;应用荧光探针2,7-二氯二氢荧光素乙酰乙酸(DCFDA)检测细胞内活性氧的变化-结果:①PPAR-酌受体激动剂罗格列酮可呈剂量依赖性的抑制醛固酮诱导的系膜细胞增殖,其抑制率可达80%以上;②醛固酮显著增加S期和G2/M细胞数,该作用可被罗格列酮阻断;③罗格列酮可呈剂量依赖性的抑制醛固酮诱导的系膜细胞cyclin D和cyclin A表达;④抗氧化剂乙酰半胱氨酸(NAC)可显著抑制醛固酮诱导的系膜细胞增殖,罗格列酮可呈剂量依赖性的抑制醛固酮诱导的系膜细胞活性氧(ROS)产生-结论:氧化应激参与醛固酮诱导的系膜细胞增殖,PPARγ激动剂通过抑制氧化应激阻断醛固酮诱导的系膜细胞增殖-

    Abstract:

    Objective:To investigate the role of oxidative stress in aldosterone(ALDO)-induced mesangial cell(MC) proliferation,and to detect the inhibitory effect of peroxisome proliferator-activated receptor--酌(PPAR-酌) agonist on ALDO-induced MC proliferation. Methods:Mouse primary mesangial cells were treated with ALDO(100 nmol/L) in the presence or absence of N-acytosistin(NAC,10 -滋mol/L)or Rosiglitazone(1.0,2.3,5.0,10.0 -滋mol/L). MC proliferation was measured by 3H-thymidine incoporation. MC cell-cycle was analyzed by flow cytometry. Cyclin D1 and cyclin A expression was determined by Western blot analysis. Reactive oxygen species(ROS)production was measured by 2’,7’-dichlorofluorescein diacetate(DCFDA) fluorescence. Results:①ALDO-induced MC proliferation was inhibited by PPAR-酌 agonist rosiglitazone in dose-dependent manner in mouse mesangial cells; ②ALDO increased cell number in S- and G2/M phase,which was inhibited by rosiglitazone; ③Rosiglitazone reduced ALDO-induced cyclin D1 and cyclin A expression in dose-dependent manner; ④NAC significantly inhibited ALDO-induced MC proliferation. Rosiglitazone dose-dependently inhibited ALDO-induced ROS production. Conclusions:ROS involved in ALDO-induced MC proliferation. PPAR-酌 ligand rosiglitazone blocked ALDO-induced MC proliferation via inhibition of ROS production.

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孙 艳,张爱华.罗格列酮阻断醛固酮诱导的肾小球系膜细胞增殖[J].南京医科大学学报(自然科学版),2008,28(11):1374-

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  • 收稿日期:2008-06-03
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