二氮嗪预处理对大鼠离体心脏缺血再灌注时心肌线粒体通透性转换孔的影响  

Effects of diazoxide preconditioning on myocardial ischemia-reperfusion induced damage to mitochondrial membrane potential and permeability transition pore in isolated rat heart

作　　者：陈其彬[1] 喻田[1] 傅小云[1] 刘兴奎[1] 张琼[1] 余志豪[1] 

机构地区：[1]遵义医学院麻醉学系,563003

出　　处：《中华麻醉学杂志》2008年第1期25-28,共4页Chinese Journal of Anesthesiology

基　　金：国家自然科学基金资助项目（30460132）

摘　　要：目的探讨二氮嗪预处理对大鼠离体心脏缺血再灌注时心肌线粒体通透性转换孔（PTP）的影响。方法健康SD大鼠72只，体重250～300g，雌雄不拘，随机分为4组（n=18），建立离体心脏Langendorf再灌注模型，K—H液平衡灌注20min后，对照组（C组）持续灌注K—H液100min不停搏；缺血再灌注组（IR组）持续灌注K—H液30min；二氮嗪预处理组（D组）依次灌注K-H液15min、二氮嗪50μmol／L10min和K—H液5min；5-羟葵酸组（5-HD组）依次灌注5-HD100μmol／L10min、K—H液5min、二氮嗪50μmol／L10min和K—H液5min。除C组外其余组于平衡后30min灌注4℃St．Thomas停搏液，全心停搏40min，再灌注30min。各组于平衡末、缺血前即刻及再灌注末随机取6个心脏测定心肌线粒体PTP半开放时间（T1/2）和线粒体膜电位。结果与平衡末、缺血前即刻相比，各组再灌注末心肌线粒体PTP T1/2缩短，膜电位降低（P〈0．05或0．01）；与C组比较，其余组心肌线粒体PTP T1/2缩短，膜电位降低（P〈0．01）；与IR组比较，D组心肌线粒体PTP T1/2延长，膜电位升高（P〈0．01），5-HD组差异无统计学意义（P〉0．05）；与D组比较，5-HD组心肌线粒体PTP T1/2缩短，膜电位降低（P〈0．05）。结论二氮嗪50μmol／L预处理可减少大鼠离体心脏缺血再灌注时心肌线粒体PTP开放，减少线粒体膜电位的丢失，维持心肌线粒体膜的完整性。Objective To investigate the effects of diazoxide preconditioning on myocardial ischemiareperfusion （I/R） induced damage to mitochondrial membrane potential and permeability transition pore （PTP） in isolated rat heart. Methods Seventy-two SD rats of both sexes weighing 250-300 g were randomly divided into 4 groups （n = 18 each） ： group Ⅰ control （C） ; groupⅡ I/R; group Ⅲ diazoxide preconditioning ＋ I/R （DIA） and group Ⅳ 5-hydroxydecanoate （5-HD） ＋ DIA. The rats were anesthetized with intraperitoneal pentobarbital 30 mg/kg. Their hearts were excised and passively perfused with oxygenated K-H solution in a Langendorff apparatus at 5.8 perfusion pressure and 37℃ via aortic cannula. In group Ⅱ- Ⅳ I/R was produced by 40 min cardiac arrest induced by 4℃ St. Thomas cardioplegic solution followed by 30 min reperfusion. In group m （DIA） the hearts were perfused with diazoxide 50 μmol/L for 10 min at 5 min before myocardial I/R while in group IV the hearts were perfused with 5-HD 100 μmol/L for 10 min at 5 min before diazoxide preconditioning. Mitochondrial membrane potential and the half time of FFP opening （ T1/2 ） were determined at the end of 20 min equilibration （To, baseline）, before ischemia （T1） and at the end of 30 min reperfusion （T2） （6 hearts at each time point）. Results Myocardial mitochondrial membrane potential was decreased while PTP opening was enhanced （shorter T1/2 ） at the end of 30 min reperfusion （T2 ） as compared with the baseline values at TO in group Ⅱ , Ⅲ and Ⅳ . In group m diazoxide preconditioning significantly attenuated the I/R-induced decrease in mitochondrial membrane potential and T1/2 . The protective effects of DIA preconditioning were aabolished to some extent by 5-HD given before DIA preconditioning. Conclusion Preconditioning with diazoxide 50 μmol/L （a mitochondrial ATP sensitive potassium channel opener） can attenuate I/R induced decrease in mitochondrial membrane potential and T1/2 in isolated

关 键 词：二氮嗪 心肌再灌注损伤 线粒体 心脏 细胞膜通透性 

分 类 号：R686[医药卫生—骨科学]