乙醛脱氢酶2抑制剂大豆甙对缺氧心肌细胞的MAPK信号转导作用  

Study of ALDH2 inhibitor daidzin role on rat myocytes MAPK singaling pathway under hypoxia

作　　者：徐丹令[1,2] 孙爱军[1] 王时俊[1] 王翔飞[1] 贾剑国[1] 顾兴华[1] 王克强[1] 邹云增[1] 葛均波[1] 

机构地区：[1]复旦大学附属中山医院上海市心血管病研究所,上海200032 [2]同济大学医学院人体解剖学教研室,上海200092

出　　处：《解剖学报》2009年第2期256-259,共4页Acta Anatomica Sinica

基　　金：上海市自然科学基金资助项目(04ZR140626)

摘　　要：目的检测乙醛脱氢酶2（ALDH2）对大鼠心肌细胞在缺氧状态下氧自由基（ROS）产生、凋亡发生和信号转导的影响。方法通过缺氧模型比较大鼠心肌细胞缺氧和经大豆甙（daidzin）24h预处理后缺氧的活性变化,用C400测定ROS,用TUNEL试剂盒检测凋亡,丝裂原活化蛋白激酶（MAPK）信号通路酶磷酸化的改变用Western blotting的方法检测。每组实验（n）均重复3次以上。结果当心肌细胞ALDH2被特异大豆甙抑制后,更易在缺氧环境下诱导产生ROS和凋亡,且与MAPK有关的磷酸化酶活性均表达增强。结论当ALDH2被抑制后,心肌细胞对缺氧的耐受性下降,这与ROS的产生、凋亡和MAPK信号通路的激活有关,ALDH2对缺氧引起的细胞改变具有保护作用。Objective To observe the role of ALDH2 on cardiac myocytes variation of reactive oxygen species （ROS）,apoptosis and mitogen-activated protein kinases （MAPK） signal route under hypoxia. Methods Cultured cardiomyocytes of neonatal rats were used. Hypoxia was imposed to the cardiomyocytes with or without daidzin pretreatment. ROS was measured by C400,apoptosis by the DeadEnd TM TUNEL system and MAPK signal pathway by Western blotting. Each group was dealt with more than three times. Results Compared to hypoxia group,that aldehyde dehydrogenase2（ALDH2） specifically inhibited by pretreated daidzin had a high frequency of ROS,apoptosis and an increased activation of MAPK signal enzymes including phosphorylated ERK1/2,JNK and P38.Conclusion The cardiac myocytes variation of ROS,apoptosis and MAPK signal path resulting from hypoxia had a close relation with ALDH2. Myocytes showed decreased tolerance to hypoxia after ALDH2 specifically inhibited by daidzin. ALDH2 prevents hypoxia myocardial injury in rat.

关 键 词：乙醛脱氢酶2 缺氧 心肌 大豆甙 丝裂原活化蛋白激酶 Western BLOTTING 大鼠 

分 类 号：R363[医药卫生—病理学]