线粒体钙激活及ATP敏感钾通道在肢体远距预处理心肌保护中的作用  

Roles of mitochondrial calcium-activated potassium channel and ATP-sensitive potassium channel in myocardial protection by limb remote preconditioning

作　　者：曹阳[1] 张世忠[1] 赵淑琴[2] 王秀静[1] 

机构地区：[1]三峡大学医学院,湖北宜昌443002 [2]三峡大学校医院,湖北宜昌443002

出　　处：《山东大学学报（医学版）》2010年第12期51-55,共5页Journal of Shandong University:Health Sciences

基　　金：三峡大学科研启动基金资助项目(0620070081)

摘　　要：目的研究心肌细胞线粒体钙激活钾通道(MitoKCa)与线粒体ATP敏感钾通道(MitoKATP)在肢体远距预处理(RPC)心肌保护中的作用。方法雄性SD大鼠72只,分为9组:单纯缺血复灌(I/R)组、RPC组、MitoKATP开放剂(DZ)组、MitoKCa开放剂NS1619组、MitoKCa开放阻断剂RPC+paxilline组、MitoKATP开放阻断剂RPC+5-HD(5-hydroxydeconate)组、RPC+NS1619+5-HD组、RPC+paxilline+DZ组和RPC+paxilline+5-HD组,每组8只。RPC模型用结扎大鼠股动脉5min,松开复灌5min,共4个循环的方法制备。各组I/R模型通过结扎离体心脏冠状动脉前降支30min,松开复灌120min进行制备。检测各组心脏血流动力学变化,TTC染色法测量心肌梗死面积,可见分光光度法检测冠脉流出液中LDH含量。结果与I/R组相比,NS1619(10μmol/L)和DZ(50μmol/L)作用与远距预处理RPC组相似,改善复灌后心功能,减小心肌梗死面积,抑制了LDH释放(P<0.01),但与RPC组相比差异无统计学意义(P>0.05)。给予Paxilline(1μmol/L)或5-HD(100μmol/L),取消了RPC的心肌保护作用(P<0.01)。阻断MitoKCa和MitoKATP中的一种通道,开放另一种通道仍可起到心肌保护作用,且与RPC组无明显差异(P>0.05);同时给予两种通道的阻断剂,发现与单独阻断一种通道相比,心肌细胞损伤程度加大(P<0.01)。结论心肌细胞线粒体钙激活钾通道MitoKCa和线粒体ATP敏感钾通道MitoKATP开放都参与了RPC的心肌保护作用,两者发挥作用的方式可能是相互独立的,但作用结果具有协同性。Objective To investigate the roles of mitochondrial calcium-activated potassium channel（MitoKCa）and mitochondrial ATP-sensitive potassium channel（MitoKATP）in myocardial protection by limb remote preconditioning（RPC）.Methods Seventy-two male Sprague Dawley rats were divided into nine groups（eight per group）：the ischemia reperfusion group（I/R）,the RPC group,the MitoKATP-channel opener group（diazoxide,DZ）,the MitoKCa-channel opener group（NS1619）,the MitoKCa inhibitor group（RPC＋paxilline）,the MitoKATP inhibitor group（RPC＋5-HD）,the RPC＋NS1619＋5-HD group,the RPC＋paxilline＋DZ group and the RPC＋paxilline＋5-HD group.Preparation of the RPC model was made by the ligation of rat’s femoral artery for 5min followed by 5min reperfusion.The procedure was repeated 4 times,the I/R model was made by the ligation of the anterior descending coronaryartery for 30min followed by 120 min reperfusion.Heart hemodynamics of each group was measured.Size of myocardium infarction was measured by TTC staining method and the content of LDH in the effusion from coronary artery was detected spectrophotometrically.Results Compared to the I/R group,administration of NS1619（10 μmol/L）and DZ（50 μmol/L）both improved heart function,decreased myocardium infarction and restrained the release of LDH（P〈0.01）,which were similar to the remote ischemic preconditioning（RPC）group（P〉0.05）.However,no difference was observed when compared with the RPC group（P〉0.05）.Administration of paxilline（1 μmol/L）or 5-HD（100 μmol/L）abolished the protective effect of RPC（P〈0.01）.When one of the two（MitoKCa and MitoKATP）channels was blocked while the other was activated,cardiac protection was still observed.And there was no significant difference when compared to the RPC group（P〉0.05）.When both channels was inhibited by the corresponding inhibitors at the same time,aggravated heart injury was noted compared to the situations in which only one of the two was blocked�

关 键 词：远距预处理 线粒体钙激活钾通道 心肌 缺血/再灌注 

分 类 号：R33[医药卫生—人体生理学]