乙醛脱氢酶2对心脏保护作用的研究

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1、复口.人学硕十学位论文乙醛脱氛酶2对心脏保护作用的研究硕士学位论文(专业学位)乙醛脱氢酶2对心脏保护作用的研究EffeetsofAldehydeDehydrogenase2onmyoeardialProtection导师葛均波教授导师组成员孙爱军副研究员邹云增教授二零零八年五月目录中文摘要··································································……1英文摘要·········，··············································

2、··········……4前言········································································……8第一部分:转染乙醛脱氢酶2基因对心衰小鼠心功能的影响材料与方法·······························································……n结果········································································……14讨论·······

3、·································································……18第二部分:药物对缺血再灌后大鼠心肌的保护作用材料与方法·······························································……24结果········································································……28讨论·······························

4、·········································……34第三部分:药物对急性心梗后心衰大鼠心功能改善影响材料与方法·······························································……41结果········································································……42讨论·····················································

5、···················……44全文小结··································································……47发表论文··································································……48致谢········································································……49乙醛脱氢酶2对心脏保护作用的研究中文摘要线粒体内的

6、乙醛脱氢酶2(ALDHZ)是线粒体氧化代谢中的主要蛋白，对乙醛代谢起着重要的作用，它能氧化乙醛，防止乙醛及活性氧(ROS)对细胞膜的脂质过氧化，减少膜蛋白的变性和线粒体DNA的损伤。我们通过转染乙醛脱氢酶2(ALDH2)腺病毒基因的方法观察到心衰(HF)小鼠心功能得到了极大的改善，心肌细胞凋亡得到抑制。在此基础上，我们选用了具有提高体内ALDHZ蛋白的解酒药物，观察其对缺血再灌(工/R)及心力衰竭(HF)模型中大鼠心脏的保护作用，为找到安全有效的心脏保护药物靶点及药物提供一定的理论依据。第一部分:转染乙醛脱氢酶2基因对心衰小鼠心功能的改善目的

7、:观察左心室腔内注射法转染乙醛脱氢酶2(ALDHZ)基因对急性心梗(AMI)后C57/BL6小鼠心功能的影响。方法:小鼠左心室注射法和急性心肌梗死(AMI)模型转染乙醛脱氢酶2腺病毒(ALDHZ，8.0x108pfu/pl/kg体重)，选用空病毒载体(blaekveCtorBy8.0XIO8pfu/pl/kg体重)和生理盐水(normalSalineNSO.4ml/kg体重)作为对照组。2周和4周时分别进行超声心动图检测，选取心衰小鼠(n=5)4周处死观察ALDHZ蛋白表达水平，免疫组化检测p53蛋白表达水平，TUNEL法检测心肌细胞凋亡。结

8、果:心脏超声结果显示，术后2周，ALDHZ组左室内径(LVEED)，左室短轴缩短率(FS)，射血分数(EF)值与NS组和BV组相比无显著差异;而术后4周，ALDHZ