基础医学与临床 ›› 2013, Vol. 33 ›› Issue (6): 744-748.

• 研究论文 • 上一篇    下一篇

马兜铃酸通过ERK1/2信号传导途径诱导人脐静脉血管内皮细胞凋亡

石红1,冯江敏2   

  1. 1. 抚顺市第二医院
    2. 中国医科大学附属第一医院
  • 收稿日期:2012-06-20 修回日期:2012-09-19 出版日期:2013-06-05 发布日期:2013-05-29
  • 通讯作者: 石红 E-mail:shihong200710085@163.com

Aristolochic acid induces apoptosis of human umbilical vein endothelial cells by suppressing the ERK1/2 signaling pathway

  • Received:2012-06-20 Revised:2012-09-19 Online:2013-06-05 Published:2013-05-29

摘要: 目的 探讨马兜铃酸(AA)是否通过ERK1/2信号传导途径诱导人脐静脉血管内皮细胞(HUVECs)凋亡。方法 通过MTT法检测细胞增殖能力;通过Hoechst 33258荧光染色观察细胞凋亡的形态学改变;通过Annexin V-FITC/PI染色采用流式细胞仪检测细胞凋亡率;通过Western blotting法测定细胞内p-ERK1/2的水平。结果 马兜铃酸呈浓度和时间依赖方式抑制了内皮细胞增殖。马兜铃酸可引起内皮细胞出现凋亡形态学改变,且呈浓度依赖方式增加了内皮细胞凋亡率。同时,马兜铃酸可降低内皮细胞内p-ERK1/2的水平。应用ERK1/2抑制剂PD98095预处理后,细胞内p-ERK1/2的水平与AA (10 mg/L)组相比显著增加,马兜铃酸诱导的内皮细胞凋亡率亦被明显抑制。结论 马兜铃酸可诱导血管内皮细胞凋亡,其机制可能是通过抑制ERK1/2信号传导途径。

关键词: 马兜铃酸, 内皮细胞, 凋亡, ERK1/2信号传导途径

Abstract: Objective To make sure whether the ERK1/2 signaling pathway plays an important role in aristolochic acid (AA) - induced the apoptosis of human umbilical vein endothelial cells (HUVECs). Methods Cell viabilities were determined by the MTT assays. Apoptotic morphologic changes of the treated cells were observed under fluorescence microscope. The proportions of apoptosis were assessed by flow cytometry. Western blotting was used to evaluate ERK1/2 phosphorylation. Results The MTT assays showed that AA significantly decreased the viabilities of HUVECs in a dose- and time-dependent manner. The flow cytometry showed that AA significantly increased the apoptosis of HUVECs in a dose-dependent manner. Microscopic apoptotic changes were also observed in these cells. Furthermore, AA inhibited ERK1/2 activation, which, however, was attenuated when the cells were pretreated with PD98095. A increase of apoptosis induced by AA was inhibited when the cells were pretreated with PD98095. Conclusion AA induces apoptosis of HUVECs via the ERK1/2 signaling pathway.

Key words: aristolochic acid, endothelial cell, apoptosis, ERK1/2 signaling pathway

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