转染乙醛脱氢酶2基因对心肌梗死后心衰小鼠心功能的影响  

Effects of Acetaldehyde Dehydrogenase 2 Transfection on Acute Myocardial Infarction Induced Heart Failure in C57BL/6 Mouse

作　　者：俞佳艳[1] 孙爱军[1] 贾建国[1] 徐丹令[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心内科,上海200032

出　　处：《中国临床医学》2008年第3期277-280,共4页Chinese Journal of Clinical Medicine

基　　金：国家863项目(2006AA02A406);国家973项目(2006CB503803和2005CB523302);国家自然科学基金杰出青年基金(30725036);上海市自然科学基金(04ZR14026)

摘　　要：目的:观察左心室腔内注射法转染乙醛脱氢酶2(ALDH2)基因对急性心肌梗死(AMI)后C57/BL6小鼠心功能的影响。方法:雄性C57BL/6小鼠分3组:(1)对照组(CON,0.1mL0.9%氯化钠);(2)转染带绿色荧光蛋白(BV)的空载体组(blankvector BV,2.0×108pfu.μL-1,0.1mL);(3)转染乙醛脱氢酶2腺病毒载体组(ALDH2,2.0×108pfu.μL-1,0.1mL)。3组小鼠闭合主动脉,左心室分别注射0.9%氯化钠或腺病毒载体,48h后结扎冠状动脉左前降支建立心肌梗死(AMI)模型。4周时分别检测超声心动图,4周处死3组小鼠(n=3)观察ALDH2表达水平,免疫组化检测p53蛋白表达水平,TUNEL法检测心肌细胞凋亡。结果:心脏超声检查显示,术后4周,ALDH2组左室舒张末内径(LVEED)显著低于CON组和BV组,左室短轴缩短率(FS)、射血分数(EF)值则显著提高(均P<0.05)。TUNEL法检测结果表明,左室梗死区域AL-DH2组凋亡细胞明显少于CON组(P<0.001)。免疫组化结果显示,ALDH2组中p53核染色阳性细胞数量远远小于CON组(P<0.001)。结论:ALDH2基因的高表达可以有效地抑制急性心肌梗死后心衰小鼠心肌细胞的凋亡,改善心脏功能,此作用可能是通过抑制p53的表达来实现的。Objective：To observe the effects of ALDH2 gene transfection on cardiac function and myocardial apoptosis in post AMI C57/BL6 mice.Methods：Male C57/BL6 mice were divided into 3 groups,each group was injected liquid to left ventricle directly：Control group（CON 0.1 mL 0.9% Sodium Chloride）,Blank Vector group（BV 2.0×10^8 pfu·μL^-1 0.1 mL GFP adenovirus）,and ALDH2 group（ALDH2 2.0×10^8 pfu·μL^-1 0.1 mL ALDH2 adenovirus）.All groups were established acute myocardial infarction（AMI） injury 48 hours after transfection.Ultrasonic cardiogram（UCG） parameters,including left ventricular end-diastolic diameter（LVEDD）,ejection fraction（EF） and fractional shortening（FS） were measured 4 weeks after operation to evaluate the cardiac function of all the mice.Heart failure mice（all n=3） were selected for further investigation.Apoptosis was measured by TUNEL assay.The expression level of p53 protein was detected by Immunohistochemistry.Results：The UCG data recorded 4 weeks after operation showed that EF and FS of ALDH2 group increased significantly while LEVDD decreased compared to controls（all P〈0.05）.The number of apoptotic cardiomyocytes in ALDH2 group was much less than CON and BV group（both P〈0.001）.Besides,the expression of p53 protein in ALDH2 group was enhanced greatly compared to controls（P〈0.001）.Conclusion：Overexpression of ALDH2 reduces myocardial apoptosis and improves cardiac function in heart failure mice,which shows a protective role of ALDH2 in heart failure.

关 键 词：乙醛脱氢酶2 急性心肌梗死 心衰 P53 细胞凋亡 

分 类 号：R541.61[医药卫生—心血管疾病]