蛋白激酶C和线粒体ATP敏感性钾通道在未成熟心肌预处理中的作用

The role of protein kinase C and mitochondrial adenosine triphosphate-sensitive potassium channel in myocardial ischemic preconditioning

目的探讨蛋白激酶C（PKC）和线粒体三磷酸腺苷敏感性钾通道（mitoKATP）在未成熟心肌预处理保护中的作用。方法采用Langendorff离体心脏灌注模型，30只新生日本长耳大白兔分为5组：缺血／再灌注组（I／R组），心脏缺血预处理组（E1组），蛋白激酶C（PKC）阻滞剂chelerythrine（CLT）＋心脏缺血预处理（E2组），mitoKATP阻滞剂5-hydroxydecanoate（5-HD）＋心脏缺血预处理（E3组），mitoKATP通道开放剂Diazoxide（Diaz）预处理组（E4组）。以血流动力学、生化指标、心肌超微结构等作为观察指标。结果E1和E4组心功能恢复、心肌含水量优于I／R、E2和E4组（P〈0．05），三磷酸腺苷含量、超氧化物歧化酶活性、心肌线粒体Ca^2＋-ATPase活性、心肌线粒体合成三磷酸腺苷（ATP）的能力优于I／R、E2和E4组（P〈0．01），丙二醛含量、血清肌酸激酶和乳酸脱氢酶漏出率、心肌细胞内Ca^2＋含量、心肌线粒体Ca^2＋含量低于I／R、E2和E4组（P〈0．01），心肌超微结构损伤较I／R、E2和E4组明显减轻。结论心肌缺血预处理对未成熟心肌具有明显的保护作用，其机制可能是通过PKC的激活和mitoKATP通道的开放起作用。

Objective To investigate the roles of protein kinase C （PKC） and mitochondrial adenosine triphosphate-sensitive potassium channel （mitoKATP） in immature myocardial ischemic preconditioning. Methods Thirty rabbits （aged 14-21 days ） were randomly divided into 5 groups： ischemic/ reperfusion group （I/R）, myocardial ischemic preconditioning group （E1）, chelerythrine group （E2）, 5- hydroxydecanoate group （ E3 ） and Diazoxide group （ E4 ）. The hemodynamics, biochemistry and myocardial uhrastructure were tested. Results Hemodynamics was improved, and myocardial water content, adenosine triphosphate content, superoxide dismutase activity, mitochondrial Ca^2＋ -ATPase activity and synthesized ATP activity of mitochondria in groups E1 and E4 were significantly increased as compared with those in groups I/R, E2 and E4. The dehydrogenase and creatine kinase leakage, malondialdehyde content, myocardial cell Ca^2＋ content and mitochondrial Ca^2＋ content in groups E1 and E4 were significantly reduced as compared with those in groups I/R, E2 and E4. The myocardial uhrastructural injury was less in groups E1 and E4 than in groups I/R, E2 and E4. Conclusion Myocardial ischemic preconditioning could obviously protect the immature myocardia by activating PKC and opening mitoKATP channels.