线粒体ATP敏感性钾通道参与超极化停搏的心肌保护作用  

Role of mitochondrial K_(ATP) channels in cardioprotection of hyperpolarized cardioplegia

作　　者：傅小云[1] 刘兴奎[1] 喻田[1] 

机构地区：[1]贵州遵义医学院麻醉学系

出　　处：《中国病理生理杂志》2008年第2期246-250,共5页Chinese Journal of Pathophysiology

基　　金：国家自然科学基金资助项目(No.30460132)

摘　　要：目的:探讨线粒体ATP敏感性钾通道(mitoKATP)开放在超极化停搏心肌保护中的作用机制。方法:将SD大鼠随机分为对照组(Control)、去极化停搏组(D)、超极化停搏组(H)、5-羟葵酸(5-HD)+去极化停搏组(5HD+D)、5-HD+超极化停搏组(5HD+H),每组8例。建立Langendorff灌注模型,平衡20 min,以不同方式停搏40 min,再灌注30 min,对比观察:(1)不同时间血流动力学变化;(2)再灌注末取心肌并分离、制备线粒体,电镜观察超微结构的变化。(3)平衡末、再灌注末线粒体活性氧的产生。结果:(1)各组再灌注末大鼠心脏功能明显低于平衡末,心肌线粒体超微结构均遭受不同程度损伤,左室发展压(LVDP)、左室舒张末压(LVEDP)、率压双乘积(DP)、冠脉流量(CF)有显著差异(P<0.01);(2)超极化停博组再灌注末心脏功能指标LVDP、LVEDP、DP、CF明显优于去极化停博组、5-HD+超极化停搏组、5-HD+去极化停搏组、对照组(P<0.01),电镜示:心肌、线粒体超微结构遭受的损伤较轻;(3)超极化停博组再灌注末心肌线粒体活性氧产生率低于对照组与其它3组(P<0.01)。结论:(1)超极化停搏能明显改善再灌注后心功能,保护心肌、线粒体超微结构,减少活性氧生成;(2)mi-toKATP的早期开放参与超极化停搏,其作用可能通过保护再灌注后的线粒体呼吸功能,减轻线粒体的氧化损伤,为再灌注心肌提供较好的能量供应,从而使缺血再灌注后的心脏收缩功能得到一定恢复。AIM： To study the protective effect of hyperpolarized cardioplegic arrest on reperfused rat heart performance and to investigate the role of mitochondrial ATP - sensitive K^＋ channels （ mitoKATP ） opening in the protection of hyperpolarized cardioplegia against ischemia/reperfusion damage. METHODS： Forty Sprague - Dawley rats were randomized into five groups （n = 8 in each group） ： control group （Con） ; depolarized arrest group （D） ; hyperpolarized arrest group （H） ; depolarized cardioplegia with 5 - hydroxydecanoate （5 - HD） group （SHD ＋ D） ; hyperpolarized cardioplegia with 5 -HD group （5HD ＋ H）. The rat hearts were quickly removed to Langendorff apparatus. The heart perfusion was performed for 20 rain with 37℃ Krebs - Henseleit buffer balanced with gas mixture （ O2：CO2 = 95% ： 5% ） at 5.8 kPa perfusion pressure, then cardial arrest was induced by different cardioplegic solution. Hearts were subjected to ischemia at 37℃ for 40 rain followed by 30 min reperfusion. （ 1 ） The hemodynamics was detected at recovery after 30 min reperfusion. （2） Before ischemia and at the end -reperfusion, tissue was harvested for mitochondrial isolation and ultrastructure was observed by transmission electron microscopy （TEM）. （3） Production of reactive oxygen species （ROS） was also determined at different time points. RESULTS： （ 1 ） Compared with end - equilibration, 30 min reperfusion caused significant differences in left ventricular developed pressure （LADP）, left ventricular end - diastolic pressure （LVEDP）, double product （ DP）, heart rate （ HR）, coronary flow （CF） （ P 〈 0. 01 ）. TEM showed that the uhrastructures of myocardial and mitochondrial were damaged remarkably. （2） When H group was compared with D, 5HD ＋ H and Con group, significant differences were found in LVDP. LVEDP. DP. HR and CF （P 〈 0.01 ）. TEM showed that the myocardial and mitochondrial uhrastructures were improved remarkably. （3） The ra

关 键 词：心脏停搏 钾通道 线粒体 活性氧 

分 类 号：R363[医药卫生—病理学]