腺苷预适应对再灌注诱导心肌细胞凋亡的影响(英文)  

Effects of adenosine preconditioning on cardiomyocyte apoptosis induced by reperfusion

作　　者：丁家望[1] 杨俊[1] 李松[1] 李稳慧[1] 陈勇[1] 李莉[1] 童晓红[1] 杨简[1] 

机构地区：[1]三峡大学第一临床医学院&湖北省宜昌市中心人民医院心内科,湖北省宜昌市443003

出　　处：《中国组织工程研究与临床康复》2007年第51期10382-10387,共6页Journal of Clinical Rehabilitative Tissue Engineering Research

摘　　要：背景:缺血再灌注损伤除导致心肌细胞坏死,还可诱发细胞凋亡,而细胞凋亡可能是梗死早期心肌细胞死亡的主要方式,也可能是心肌梗死面积扩大的原因之一。目的:观察腺苷预适应在缺血再灌注的抗心肌细胞凋亡效应,探讨凋亡相关基因蛋白Bcl-2和Bax在其中的作用。设计:随机对照的动物实验。单位:三峡大学第一临床医学院湖北省宜昌市中心人民医院心内科。材料:选用健康雄性家兔36只,清洁级,体质量2.5￣3.0kg,由华中科技大学同济医学院实验动物学部提供。实验过程中对动物的处置符合动物伦理学标准。按随机数字表法将实验动物分为3组:对照组、腺苷预适应组和腺苷A1受体拮抗剂组,每组12只。方法:实验于2005-10/2006-10在三峡大学中心实验室完成。制备离体家兔心肌缺血再灌注模型。将动物麻醉后,肝素抗凝,行Langendorff逆行灌注。对照组:缺血40min,再灌注60min;灌注结束后将其中6只家兔用于确定心肌梗死范围,另外6只用作心肌细胞凋亡、基因表达和心肌组织超微病理的分析。腺苷预适应组:在缺血前30min给予腺苷10μmol/L持续灌流,其余同对照组。腺苷A1受体拮抗剂组:缺血前45min给予腺苷A1受体阻滞剂10mmol/L灌流15min后,与腺苷预适应组采取相同措施。主要观察指标:①观察缺血再灌注过程中3组动物的心率和血压。②用氯化三苯基四氮唑确定心肌梗死范围。③采用末端标记法和DNA琼脂糖凝胶电泳检测心肌细胞凋亡指数。④原位免疫组化检测凋亡相关蛋白Bcl-2和Bax的表达。结果:纳入的36只家兔全部进入结果分析。①心率和血压比较:在缺血再灌注过程中,心率和血压均持续下降,差异有显著性意义(P<0.01)。组间比较,差异无显著性意义(P>0.05)。②心肌梗死范围比较:对照组、腺苷预适应组和腺苷A1受体拮抗剂组缺血心肌范围比较,差异无显著性意义(P>0.05)。腺苷预BACKGROUND: Ischemia/reperfusion injury can cause the necrosis of cardiomyocyte, and it can also induce cell apoptosis. However, cell apoptosis may be the main death type of cardiomyocyte at the early stage of infarction, and it may be one of causes for expanding myocardial infarction area. OBJECTIVE: The goal of this study was to observe the anti-apoptotic effect of adenosine (ADO) preconditioning on cardiomyocytes during the ischemia/reperfusion, and to investigate the role of apoptosis-related gene protein Bcl-2 and Bax. DESIGN: A randomized controlled animal experiment. SETTING: First College of Clinical Medical Science, China Three Gorges University&Department of Cardiology, Yichang Central People's Hospital. MATERIALS: Thirty-six healthy male rabbits of clean grade, weighing 2.5 to 3.0 kg, were provided by Laboratory Animal Department, Tongji Medical College, Huazhong University of Science and Technology. The protocol was carried out in accordance with animal ethics guidelines for the use and care of animals. All rabbits were divided into 3 groups according to random number table. There were 12 animals in either control, ADO or ADO+DPCPX (an adenosine A1 receptor antagonist). METHODS: This experiment was carried out in the Central Laboratory, China Three Gorges University between October 2005 and October 2006. Ex vivo rabbit myocardial ischemia/reperfusion models were prepared. After being anesthetized, the rabbits were performed anticoagulation with heparin and carried out Langendorff retroperfusion. In the control group, the hearts of animals subjected to 40 minutes of ischemia and 60 minutes of reperfusion. Six of them were used for determining myocardial infarct size after reperfusion, another six for cardiomyocyte apoptosis, gene expression and ultrastructural analysis of myocardium. In the ADO group: The ADO hearts were continuously infused with 10 μmol/L of adenosine 30 minutes before ischemia, and operated according to the requirement of control group. In the DPCPX group: the isolated hearts of ani

关 键 词：凋亡 再灌注损伤 腺苷预适应 腺苷A1受体 BCL-2 Bax] 

分 类 号：R542.2[医药卫生—心血管疾病]