线粒体钙激活钾通道参与远距缺血预处理心肌保护机制研究  

Research on the mechanism of mitochondrial calcium-activated potassium channel in myocardial protection by remote preconditioning

作　　者：曹阳[1] 赵淑琴[2] 张世忠[1] 陈慧颖[1] 

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

出　　处：《临床心血管病杂志》2010年第9期701-704,共4页Journal of Clinical Cardiology

基　　金：三峡大学科研启动基金(No:0620070081)

摘　　要：目的:研究线粒体钙激活钾通道在大鼠肢体远距缺血预处理(RPC)对缺血再灌注心肌损伤保护中的作用机制。方法:分离大鼠右下肢股动脉,结扎5min,松开复灌5min,共4个循环。取出心脏悬挂于Langen-dorff灌流装置,全心停灌30min,复灌120min。分离心肌细胞线粒体,电镜观察心肌线粒体结构变化;检测不同处理组线粒体膜电位、线粒体内NOS、Mn-SOD、Ca2+含量的变化。结果:与单纯缺血复灌组相比,RPC组和钙激活钾通道开放剂NS1619组心脏复灌后心肌线粒体损伤减轻,内外膜结构较完整;心肌细胞线粒体膜电位增加(P<0.01)、Mn-SOD含量增高(P<0.01),NOS含量降低(P<0.01)、Ca2+含量下降(P<0.01);与RPC组相比,RPC与钙激活钾通道开放阻断剂Paxilline联合组各指标有明显差异(P<0.01)。结论:心肌线粒体钙激活钾通道可能通过维持线粒体膜电位,减少心肌复灌期线粒体NO生成和Ca2+含量升高,提高线粒体抗氧化能力而在肢体RPC心肌保护发挥作用。Objective：To investigate the underlying mechanisms of mitochondrial calcium-activated potassium channel（MitoKCa）in myocardial protection by limb remote preconditioning（RPC）.Method：The right femoral artery of the rats was ligated for 5min followed by 5min reperfusion totally 4cycles as RPC model,Rat hearts were Langendorff perfused,subjected to 30min of global ischemia and 120min of reperfusion.At the end of reperfusion,the ultrastructure of mitochondria was observed by using electron microscope;The mitochondria was isolated and the mitochondrial membrane potential was measured by using fluorospectrophotometry method and the contents of NOS、Mn-SOD、Ca2＋in mitochondria was measured spectrophotometrically,separately.Result：Compared to ischemia/reperfusion group,the injury of mitochondrial was decreased;mitochondria cristae were relatively integrity;mitochondrial membrane potential was maintained（P0.01）,the contents of Mn-SOD increased（P0.01）but NOS（P0.01）and Ca2＋（P0.05）decreased in RPC and MitoKCa opener NS1619（10μmol/L）treatment groups.There was significant difference between RPC group and RPC plus MitoKCa inhibitor Paxilline（1μmol/L）treatment group（P0.01）.Conclusion：MitoKCa may participate in cardioprotection by limb RPC via maintaining of mitochondrial membrane potential,decreaseing the production of NO and the content of calcium in mitochondria during reperfusion,and increasing the antioxidant ability of myocardium.

关 键 词：缺血预处理 线粒体 钙激活钾通道 心肌 

分 类 号：R541.4[医药卫生—心血管疾病]