线粒体心磷脂在二氮嗪预处理减轻大鼠离体心脏缺血再灌注损伤中的作用  

Role of mitochondrial cardiolipin in the protective effects of diazoxide preconditioning on isolated rat hearts against ischemia-reperfusion injury

作　　者：邓胜利[1] 喻田[1] 刘兴奎[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》2009年第5期453-456,共4页Chinese Journal of Anesthesiology

基　　金：国家自然科学基金资助项目（30460132）

摘　　要：目的评价线粒体心磷脂在二氮嗪预处理减轻大鼠离体心脏缺血再灌注损伤中的作用。方法清洁级SD大鼠72只，体重200—280g，雌雄各半，随机分为对照组（C组）、缺血再灌注组（I／R组）、二氮嗪预处理组（DZ组）和5-羟葵酸拮抗二氮嗪组（HD组），每组18只。采用Langendorff灌流装置建立大鼠离体心脏缺血再灌注模型，C组平衡灌注20min，持续灌注100min；I／R组平衡灌注20min，持续灌注30min，缺血40min，再灌注30min；DZ组平衡灌注20min后，依次灌注K-H液15min、50μmol／L．二氮嗪10min和K-H液5min，其余缺血再灌注同I／R组；HD组二氮嗪预处理前给予含5．羟葵酸100μmol／LK-H液10min，其余处理同DZ组。各组分别于平衡灌注末（T1）、缺血前即刻（T2）、再灌注末（L）时随机取6只大鼠，监测心率（HR）、左心室发展压（LVDP）和左心室舒张末压（LVEDP），采用高效液相色谱仪测定心肌线粒体心磷脂含量。结果与T1,2时比较，各组L时HR、LVDP降低，LVEDP升高，心肌线粒体心磷脂含量降低（P〈0．05）；与C组比较，其余3组B时HR、LVDP降低，LVEDP升高，心肌线粒体心磷脂含量降低（P〈0．05）；与I／R组比较，DZ组T3时HR、LVDP升高，LVEDP降低，心肌线粒体心磷脂含量升高（P〈0．05）；与DZ组比较，HD组L时HR、LVDP降低，LVEDP升高，心肌线粒体心磷脂含量降低（P〈0．05）。结论二氮嗪预处理可减轻大鼠离体心脏缺血再灌注损伤，与维持心肌线粒体心磷脂含量有关。Objective To investigate the role of mitochondrial cardiolipin in the protective effects of diazoxide preconditioning on isolated rat hearts after ischemia-reperfusion （I/R）. Methods Seventy-two healthy SD rats of both sexes （36 male, 36 female） weighing 200-280 g were randomly divided into 4 groups （ n = 18 each）： group Ⅰ control （group C）; group Ⅱ I/R; group Ⅲ diazoxide preconditioning ＋ I/R （group DZ ＋ I/R） and group Ⅳ 5-hydroxydeconoate （group 5-HD） ＋ DZ ＋ I/R （group 5-HD ＋ DZ ＋ I/R）. The animals were anesthetized with intraperitoneal pentobarbital 40 mg/kg. Their hearts were excised and passively perfused in a Langendorffapparatus with oxygenated K-H solution at 5.8 kPa and 37℃. Left ventricular developed pressure （LVDP） was measured from a fluid filled latex balloon inserted in the left ventricle. After 20 min of stabilization the isolated hearts were subjected to 40 rain ischemia followed by 30 min reperfusion in group Ⅱ . In group Ⅲ the isolated hearts were perfused with diazoxide 50 μmol/L for 10 min before I/R and in group IV the isolated hearts were perfused with 5-HD 100μmol/L for 10 min before diazoxide preconditioning. HR, LVDP and left ventricular end-diastolic pressure （LVEDP） were recorded and mitochondrial cardiolipin content in myocardium was measured at the end of 20 rain stabilization （ T1 , baseline）, immediately before ischemia （ T2 ） and at the end of 30 min reperfusion （T3 ） （6 animals at each time point）. Results I/R significantly decreased HR and LVDP and increased LVEDP and decreased mitochondrial cardiolipin content in myocardium at T3 as compared with the baseline values before ischemia at T1 and T2 in group Ⅱ . Diazoxide preconditioning significantly attenuated the I/R induced effects. The protective effects of diazoxide preconditioning against I/R injury was counteracted by 5-HD, a specific mitochondrial ATP sensitive potassium channel blocker. Conclusion Diazoxide preconditioning ean protect the my

关 键 词：二氮嗪 线粒体 心脏 再灌注损伤 心磷脂质类 

分 类 号：R654.2[医药卫生—外科学] R614[医药卫生—临床医学]