乙醛脱氢酶2对小鼠缺氧心肌细胞的抗凋亡作用  

The anti-apoptotic role of Aldehyde dehydrogenase 2 in mice hypoxia cardiac cells

作　　者：易春秀 张玄子 周润露 莫金鑫 赵雅静[1] YI Chunxiu;ZHANG Xuanzi;ZHOU Runlu;MO Jinxin;ZHAO Yajing(Department of Cardiology,the Second Affiliated Hospital of Kunming Medical University,Kunming,Yunnan 650101,China)

机构地区：[1]昆明医科大学第二附属医院心内科

出　　处：《重庆医学》2020年第4期526-530,共5页Chongqing medicine

基　　金：云南省教育厅科学研究基金项目重点项目（2015Z078）

摘　　要：目的观察乙醛脱氢酶2(ALDH2)在小鼠缺氧心肌细胞凋亡中所起的作用并探讨其机制。方法36只小鼠分为3组,第1组和第2组小鼠离体心脏分别用4-羟壬烯醛(4-HNE)灌流+缺血再灌注组和生理盐水灌流(缺血再灌注组),两组小鼠均灌流30 min后关闭灌流管造成全心缺血30 min后再打开灌流管灌流45 min,第3组(4-HNE灌流组)小鼠用4-HNE持续灌流75 min,分别测定3组小鼠离体心脏的细胞凋亡指数。接下来将腺病毒转染法制备的另外36只小鼠野生型、ALDH2基因高表达型及ALDH2基因敲除型3组模型均结扎左前降支造成小鼠心肌梗死。4周后解剖小鼠,每组随机选取6只小鼠用于测定心梗小鼠心肌梗死面积,每组剩下的6只小鼠则提取左心室组织测定4-HNE的表达水平。结果(1)4-HNE灌流+缺血再灌注组小鼠离体心脏细胞凋亡指数大于4-HNE灌流组(P<0.01)和缺血再灌注组(P<0.01),4-HNE灌流组与缺血再灌注组小鼠心肌细胞凋亡指数差异无统计学意义(P>0.05)。(2)4-HNE在ALDH2基因敲除型小鼠缺氧心肌细胞中的表达高于ALDH2基因高表达型(P<0.05),在野生型中的表达介于两者之间(P<0.05)。(3)ALDH2基因敲除型小鼠心肌梗死面积高于ALDH2基因高表达型(P<0.01),而野生型的小鼠心肌梗死面积介于两者之间(P<0.01)。结论ALDH2通过分解4-HNE减轻小鼠缺氧心肌细胞的凋亡。Objective To evaluate the anti-apoptotic effect of aldehyde dehydrogenase 2(ALDH2)in mice hypoxia cardiac cells and to explore the mechanism.Methods Thirty-six mice were classified into three groups at random.All mice′s hearts have been isolated.Those of ischemia/reperfusion(I/R)group were perfused with normal saline and those of 4-hydroxy nonanel(4-HNE)+I/F group were perfused with 4-HNE.These two groups both experienced a period of 30 minutes ischemia followed by a perfusion period of 45 minutes.While the mice hearts of 4-HNE group were perfused with 4-HNE persistently for 75 minutes.The apoptosis index of cardiac cells in the three groups were measured.Then the other thirty-six mice were classified as wild type,ALDH2 gene over-expression type and ALDH2 gene knockout type by adenovirus transfection methods.Mice myocardial ischaemia model was induced by ligating left anterior descending coronary.Six mice have been chosen at random from each group to measure the expression of 4-HNE after four weeks.The area of myocardial infarction(MI)of the rest six mice in the three groups were measured.Results(1)The cardiac cell apoptosis index of 4-HNE+I/R group is higher than that of 4-HNE group(P<0.01)and I/R group(P<0.01).But there was no significant difference between the 4-HNE group and the I/R group in the cardiac cell apoptosis index(P>0.05).(2)The expression of 4-HNE group in the infarcted heart was obviously higher in ALDH2 knockout mice than that of wild type(P<0.05).While there was less expression of the ALDH2 over-expression group than that of wild type(P<0.05).(3)The area of myocardial infarction of ALDH2 gene knockout group is higher than that of ALDH2 gene over-expression group(P<0.01).While the area of myocardial infarction of wild type is less than that of ALDH2 gene over-expression group and more than that of ALDH2 gene knockout group(P<0.01).Conclusion ALDH2 antagonize the apoptosis from hypoxia injury by the detoxification of 4-HNE.

关 键 词：乙醛脱氢酶2 4-羟壬烯醛 缺氧心肌细胞 凋亡 

分 类 号：R541.4[医药卫生—心血管疾病]