缺血预处理对大鼠离体缺血再灌注心脏心肌功能和线粒体ATP敏感性钾通道的影响  

Effect of ischemic preconditioning on cardiac function and mitochondrial K_(ATP) channel of isolated heart following ischemia- reperfusion in rats

作　　者：季永[1] 喻田[1] 李宗权[1] 刘兴奎[1] 陈其斌[1] 余志豪[1] 

机构地区：[1]遵义医学院麻醉学教研室,徐州医学院附属医院麻醉科563003

出　　处：《中华麻醉学杂志》2006年第3期238-241,共4页Chinese Journal of Anesthesiology

基　　金：国家自然科学基金资助项目(30460132)

摘　　要：目的研究缺血预处理(IP)对大鼠离体心脏缺血再灌注损伤的保护作用机制。方法 Wistar大鼠48只,其中40只随机分为缺血再灌注组(I/R组)、IP组、二氮嗪组(DZ组)、5-羟葵酸(选择性线粒体ATP敏感性钾通道阻滞剂)拮抗IP组(5-HD+IP组)、5-羟葵酸拮抗二氮嗪组(5-HD+DZ 组),每组8只,另外8只用作正常心肌线粒体电镜检查对照组。应用Langendorff离体心脏灌注系统建立心脏缺血再灌注模型,平衡灌注20 min后,30 min预处理期间各组进行以下处理,IP组进行2次缺血再灌注,灌注压8．5 kPa,灌注速率8．5 ml／min。每次IP缺血5 min再灌注5 min;DZ组灌注50 μmol ·L-1二氮嗪;5-HD+IP组灌注100 μmol·L-1 5-羟葵酸10 min,然后给予2次IP;5-HD+DZ组灌注5-羟葵酸100μmol-L-1 10min,再灌注二氮嗪50μmol·L-1 10min。然后各组全心缺血40min,再灌注30min。持续测定心功能指标[心率、左心室发展压(INDP)、左心室舒张末压(INEDP)和冠脉流量(CF)],再灌注末取心肌,提取线粒体,电镜下观察其病理学改变,并进行线粒体Flameng评分。结果与I／R组比较,IP和二氮嗪预处理能明显提高再灌注期间LVDP,降低LVEDP,降低心肌线粒体Flameng评分(P< 0．01),减轻心肌病理学损伤;5-羟葵酸能部分拮抗IP、完全拮抗二氮嗪预处理对心肌缺血再灌注损伤的保护作用。结论 IP对心肌缺血再灌注损伤的保护作用与线粒体ATP敏感性钾通道的激活有关。Objective To investigate the role of mitochondrial KATP channel in the mechanism of the protective effect of ischemic preconditioning （IP） against ischemia-reperfusion （I/R） injury. Methods Forty-eight Wistar rats of beth sexs weighing 250-350 g were used in this study. Forty rats were randomly divided into 5 groups （ n = 8 each） ： group A I/R; group B IP＋ I/R; group C diazoxide （DZ mito-KATP channel activator） ＋ I/R; group D 5-HD （mito-KATP channel blocker） ＋ IP＋ I/R and group E 5-HD＋ DZ＋ I/R. Another 8 animals were used for electron microscopic examination of normal mitochondria as control. The animals were anesthetized with intraperitoneal pentubarbital 30 mg· kg^-1 . The hearts were immediately excised and passively perfused in a Langendorff apparatus with K-H solution at 5.8 kPa perfusion pressure and 36.5-37.5℃ via aortic cannulation. A fluid-fdled latex balloon was via left atrium in left ventricle for the measurement of left ventricular function. I/R was induced after 30 min stabilization by clamping aortic cannula for 40 min followed by 30 min reperfusion. In group B and D the isolated hearts underwent 2 episodes of 5 min ischemia followed by 5 min reperfusion before I/R. In group C and E DZ 50μmol·L^-1 was infused for 10 rain and in group D and E 5-HD 100 μmol·L^-1 was infused for 10 rain before I/R. HR, LVSP, LVEDP and coronary flow （CF） were measured at the end of stabilization （To, baseline）, immediately before I/R （3＂1） and at 10, 20 and 30 min of reperfusion （T2.3.4）, and left ventricular developed pressure （LVDP = LVSP- LVEDP） was calculated. Myocardial tissue was obtained at the end of 30 min reperfusion for electron microscopic examination of mitochondria. Mitocbendrial ultrastructure was assessed by Flameng scoring system （0 = normal, 4 = severely damaged ） .Results Ischemic and DZ preconditioning significantly increased LVDP and decreased LVEDP and Flameng score. 5-HD pretreatment partly antagonized the protective effect of IP

关 键 词：心肌缺血 缺血预处理 心肌再灌注损伤 线粒体 心脏 钾通道 腺苷三磷酸酶 

分 类 号：R541[医药卫生—心血管疾病]