基础医学与临床 ›› 2008, Vol. 28 ›› Issue (2): 167-171.

• 研究论文 • 上一篇    下一篇

顺铂诱导肾小管上皮细胞毒性及Bcl-2对抗细胞凋亡作用机理研究

冯乐平 乔 伟 ZHANG Dong   

  1. 桂林医学院 生物技术学院 桂林医学院 生物技术学院 佐治亚医学院
  • 收稿日期:2007-04-05 修回日期:2005-06-12 出版日期:2008-02-25 发布日期:2008-02-25
  • 通讯作者: 冯乐平

Studies of the RPTC Cells Toxicity Induced by Cisplatin and Bcl-2 Anti-Apoptosis Mechanism

Le-ping FENG, Wei QIAO, Dong ZHANG   

  • Received:2007-04-05 Revised:2005-06-12 Online:2008-02-25 Published:2008-02-25
  • Contact: Le-ping FENG,

摘要: 【摘要】 目的 通过转染不同畸变的Bcl-2基因,探讨顺铂诱导RPTC细胞凋亡的作用机理和Bcl-2基因抑制顺铂诱导细胞凋亡的作用途径。方法 应用不同亚细胞结构分布的Bcl-2基因体外转染肾小管上皮细胞(RPTC),根据共聚焦显微技术和免疫荧光技术分析Bcl-2(X)基因表达产物在RPTC细胞线粒体和内质网上的分布定位,以及采用Hoechst33258染色并进行细胞凋亡计数的统计情况,研究顺铂诱导细胞凋亡的信号传导途径。结果 通过基因转染发现,不同畸变组分的Bcl-2(Bcl-acta,Bcl-cb5)分别定位于RPTC细胞的线粒体、内质网上,Bcl-nt则同时定位于上述两种细胞器上。Bcl-cb5组可见更多的Bax被激活,同时可见较多的碎裂细胞核。统计发现,定位于线粒体上的Bcl-acta明显抑制顺铂对RPTC细胞诱导的细胞凋亡(P<0.05)。结论 顺铂可以明显诱导RPTC细胞凋亡,而且这种凋亡的信号传导途径主要通过线粒体途径进行。Bcl-2抑制顺铂诱导细胞凋亡也主要是通过线粒体途径而起作用。

关键词: 细胞凋亡, 顺铂, Bcl-2基因, 细胞信号传导

Abstract: 【Abstract】 Objective To study the mechnism of toxicity by cisplatin on RPTC cell line and Bcl-2 anti-apoptosis mechanism with transfection of different mutant Bcl-2 in vitro. Methods RPTC cell was translocated with different mutant Bcl-2(s). The cell apoptosis induced by cisplatin on RPTC ce11 were analyzed with confocal and flurencent microscope.the cell apoptosis was measured with Hoechst33258 after treated with cisplatin. Results Different mutant Bcl-2(Bcl-acta,Bcl-cb5)were translocated on mitochondrial and Endoplasmic Reticulum(ER) respectively.Bcl-acta can protect RPTC cell from apoptosis easily more than Bcl-cb5 group in time-dependant manner by cisplatin treated (P<0.05). Conclusion Cisplatin can induced RPTC cell apoptosis obivously by mitochondrial signaling payhway and Bcl-2 have protect more RPTC cell from apoptosis in mitochondrial manner other than in ER.

Key words: Cell apoptosis, Cisplatin, Bcl-2 gene, Signaling transduction