二氮嗪后处理对离体大鼠心功能及线粒体心磷脂的影响  

Effect of diazoxide postconditioning on cardiac function and mitochondrial cardiolipin in isolated rat heart

作　　者：段忠心[1,2] 刘兴奎[1] 喻田[1] 

机构地区：[1]遵义医学院麻醉系,贵州遵义563003 [2]南华大学附属第二医院麻醉科,湖南衡阳421001

出　　处：《中国病理生理杂志》2015年第5期812-816,共5页Chinese Journal of Pathophysiology

基　　金：国家自然科学基金资助项目(No.30740044);贵州省科技基金资助项目[(2007)2121号]

摘　　要：目的:建立离体大鼠心肌缺血/再灌注损伤模型,观察二氮嗪(diazoxide,D)后处理对缺血/再灌注损伤离体大鼠心功能及线粒体心磷脂的影响,并探讨ATP敏感性钾通道在二氮嗪后处理心肌保护中的作用。方法:采用Langendorff装置建立离体大鼠心肌缺血/再灌注损伤模型,将SD大鼠随机分为对照组(control)、缺血再灌注模型组(I/R)、二氮嗪后处理组(I/R+D)、5-羟葵酸拮抗二氮嗪后处理组(I/R+5-HD+D),每组8只,均先灌注平衡20 min。Control组:灌注平衡后续灌70 min;I/R组:缺血前灌注4℃ST.Thomas停跳液,全心缺血40 min,再灌30 min;I/R+D组:全心缺血40 min,缺血后给予含二氮嗪(50μmol/L)的K-H液灌注5 min后,再灌25 min;I/R+5-HD+D组:二氮嗪后处理前给予含5-羟葵酸(100μmol/L)的K-H液灌注5 min,再灌20 min。观察各组续(再)灌注末心率、冠脉流出液量、心功能、心肌酶学及心肌线粒体心磷脂的变化。结果:各组续(再)灌注末比较,I/R组较control组及I/R+D组心率减慢、冠脉流出液量降低,心功能明显受损,心肌酶增加,心磷酯含量减少,但与I/R+5-HD+D无明显差异。结论:二氮嗪后处理通过增加线粒体心磷脂含量,减少心肌酶的释放,改善心脏功能,减轻心肌的再灌注损伤,产生心肌保护作用。5-羟葵酸能够完全阻断二氮嗪的心肌保护作用。AIM： To investigate the effect of diazoxide （D） postconditioning on Cardiac function and mito-chondrial cardiolipin in isolated rat heart and to explore the protective effect of ATP sensitive potassium channel on diazo-xide postconditioning myocardium.METHODS： The myocardial ischemia/reperfusion injury model in isolated rat hearts was established by Langendorff apparatus.The isolated rat hearts were randomized into 4 groups （ n=8）： control group （ control） , myocardial ischemia/reperfusion injury group （ I/R） , diazoxide postconditioning group （ I/R＋D） , 5-hydroxy decanoic acid （5-HD） plus diazoxide postconditioning group （I/R＋5-HD＋D）.The hearts in each group were started with 20 min perfusion for equilibration.The hearts in control group perfused for 70 min;The hearts in I/R group was global ischemia for 40 min after ischemia reperfusion at 4℃ST.Thomas cardioplegia, then reperfusion for 30 min;The hearts in I/R＋D group were treated with diazoxide （50μmol/L） in K-H perfusion for 5 min after global ischemia for 40 min, then reperfusion for 25 min;The hearts in I/R＋5-HD＋D group were treated with 5-HD （100μmol/L） in K-H perfusion for 5 min before diazoxide postconditioning, then reperfusion for 20 min.The heart rate, coronary outflow volume, heart func-tion, myocardial enzymes and myocardial mitochondrial cardiolipin at the end of perfusion in each group were determined. RESULTS：Compared with control group and I/R＋D group, the heart rate, the concentration of heart phospholipid and the coronary outflow volume were reduced, the heart function was significantly impaired the contents of myocardial enzymes were increased in I/R group.However, no significant difference between I/R group and I/R＋5-HD＋D group was ob-served.CONCLUSION：The diazoxide postconditioning protects the myocardium by increasing mitochondrial cardiolipin content, reducing the release of myocardial enzymes, improving heart function and reducing myocardial reperfusion injury. The myoca

关 键 词：心磷脂 二氮嗪 缺血/再灌注损伤 

分 类 号：R363[医药卫生—病理学]