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黄芪甲苷抑制高糖诱导的足细胞凋亡作用及机制(1)
http://www.100md.com 2010年4月1日 桂定坤1, 陈建国1, 陈宜方1 , 黄建华2
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    参见附件。

     (1.浙江医院肾内科, 浙江 杭州 310013; 2.复旦大学附属华山医院中西医结合研究所, 上海 200040)

    摘 要:目的:探讨黄芪甲苷(AS-IV)对高糖诱导的足细胞凋亡的作用及其机制。方法:条件性永生的小鼠足细胞分为正常糖组(NG)、高糖组(HG)、甘露醇高渗对照组(MA)及HG+不同剂量(10、50、100 μg/mL)黄芪甲苷干预组(AS-IV)。流式细胞仪及Hoechst染色检测细胞凋亡;荧光探针CM-H2-DCF-DA标记细胞检测活性氧(ROS)水平;Western印迹检测足细胞p38-MAPK活性。结果:高糖促进足细胞ROS的产生并引起足细胞凋亡,AS-IV明显抑制高糖诱导的ROS的产生及足细胞凋亡,且呈剂量依赖关系。此外,高糖激活p38-MAPK信号通路,AS-IV呈剂量依赖性抑制p38-MAPK活性。结论: AS-IV能减少高糖所致的足细胞凋亡,其机制可能与AS-IV抗氧化及抑制p38-MAPK活化密切相关。

    关键词:黄芪甲苷;高糖;足细胞;凋亡;活性氧;p38-MAPK

    中图分类号:R285.5 文献标识码:A 文章编号:1673-7717(2010)04-0822-03

    Astragaloside IV Inhibited High Glucose-Induced Podocyte Apoptosis and Its Mechanism

    GUI Dingkun1,CHEN Jianguo1,CHEN Yifang1,HUANG Jianhua2

    (1.Department of Nephrology, Zhejiang Hospital, Hangzhou 310013,Zhejiang,China;

    2.Institute of Integrated Chinese and Western Medicine, Huashan Hospital, Fudan University, Shanghai 200040, China)

    Abstract:Objective: To study the effects of Astragaloside IV(AS-IV) on glucose-induced apoptosis of podocytes and explore its possible mechanism. Methods: Conditionally immortalized mouse podocytes were divided into nomal glucose group (NG) , high glucose group (HG), mannitol group (MA) and HG with 10, 50 and 100 μg/mL of AS-IV for 24h.Flow cytometry and Hoechst staning were used for the quantification of apoptotic podocytes. Reactive oxygen species (ROS) generation was measured with the fluoroprobe carboxymethyl-H2-dichlorofluorescein diacetate. The activation of p38-MAPK was determined by Western blot. Results: HG induced ROS generation and apoptosis of podocytes. AS-IV inhibited HG-induced ROS generation and apoptosis of podocytes in a dose-dependent manner. Moreover, HG caused p38-MAPK activation in podocytes, while AS-IV dose-dependently inhibited p38-MAPK activation.Conclusion: Astragaloside prevented high glucose-induced podocyte apoptosis and this effect may be involved in inhibition of ROS and p38-MAPK.

    Key words:Astragaloside IV; high glucose; podocyte; apoptosis; ROS;p38-MAPK

    收稿日期:2009-11-11

    基金项目:浙江省老年医学重点学科群计划项目(2008ZJ006) ......

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