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 rate of ROS generating was lower in group H than that in other four groups at end - reperfusion （ P 〈 0. 01 ）. CONCLUSION ： （ 1 ） Of the four cardioplegias, hyperpolarized cardioplegia is superior to improve myocardial performance, attenuates myocardial and mitochondrial injury, and reduces rate of ROS generating. （2） Mitochondrial preservation is one of mechanisms of myocardial protection in hyperpolarized cardioplegia, opening of mitoKATP enhances cardioprotection through decreasing ROS generating, providing better energe supply for reperfused myocardium.
出处
《中国病理生理杂志》
CAS
CSCD
北大核心
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)
关键词
心脏停搏
钾通道
线粒体
活性氧
Heart arrest
Potassium channels
Mitochondria
Reactive oxygen species
