M受体对H_2O_2诱导PC12细胞凋亡的保护作用及机制  

Protective effects of muscarinic receptor on apoptosis of PC12 cells induced by hydrogen peroxide

作　　者：江伟健[1] 赵灵芝[2] 黄亦俊[1] 邱鹏新[1] 颜光美[1] 

机构地区：[1]中山大学中山医学院药理学教研室,广东广州510080 [2]中山大学药学院药理毒理实验室,广东广州510080

出　　处：《中国药理学通报》2005年第8期930-934,共5页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金(No39900181);国家杰出青年科学基金(No39625022);广东省自然科学基金(No2KM028091)资助项目

摘　　要：目的研究毒蕈碱型胆碱受体在抗氧化应激所诱导的凋亡中不同亚型之间是否存在差异。方法用含有M1M4毒蕈碱型胆碱受体亚型的质粒pCDNA3.0转染PC12细胞,加入过氧化氢诱导凋亡,观察氨甲酰胆碱激动毒蕈碱型胆碱受体后各亚型之间抗凋亡能力是否存在差异,同时应用毒蕈碱型胆碱受体抑制剂阿托品,ERK和PI3K信号通路抑制剂PD98059与LY294002观察参与保护作用的相关的信号通路。结果氨甲酰胆碱激动毒蕈碱型胆碱受体后产生抗凋亡效应,各亚型之间没有差异,PI3K信号通路参与了保护作用。结论M1M4亚型毒蕈碱型胆碱受体在对抗过氧化氢诱导的凋亡没有亚型之间的差异,PI3K信号通路参与了保护作用。Aim To find out the relationship between muscarinic receptor and reactive oxygen species （ROS） and the probable differences between the four muscarinic receptor subtypes. Methods We transfected the plasmid encoding muscarinic receptor （including subtypes： M1, M2, M3 and M4） into PC12 cells. Then PC12 cells were exposed to hydrogen peroxide （H2O2 ） , carbachol and other inhibitors such as atropine, LY294002 and PD98059. Results The resuits showed that activation of muscarinic receptor by carbachol protected PC12-M1 , PC12-M2,PC12-M3 and PC12-M4 cells from apoptosis induced by H2O2. There was no statistical difference in the protective effect between these four muscarinic receptor subtypes. By using the inhibitors, we found that atropine and LY294002 blocked the protective effect of activation of muscarinic receptor on apoptosis induced by H2O2.Conclusion Activation of muscarinic receptor retarded the apoptosis induced by H2O2. There was no difference between the four muscarinic receptor subtypes. The protective effect was mainly mediated by the activation of muscarinic receptor and phosphatidylinositol-3 kinase （PI3K）.

关 键 词：凋亡 毒蕈碱型胆碱受体 活性氧 PC12细胞 PI3K 

分 类 号：R329.24[医药卫生—人体解剖和组织胚胎学] R329.25[医药卫生—基础医学]