线粒体三磷酸腺苷敏感性钾通道在未成熟心肌缺血预处理中的作用

The Role of Mitochondrial Adenosine Triphosphate-sensitive Potassium Channel in Immature Myocardial Ischemic Preconditioning

目的探讨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，为未成熟心肌的保护提供依据。方法采用Langendorff离体心脏灌注模型，将24只新生（出生14～21d）日本长耳大白兔按随机数字表法分为4组：缺血／再灌注组（I／R组），心脏缺血预处理组（E1组），mitoKATP阻滞剂5-hydroxydecanoate（5-HD）＋心脏缺血预处理（E2组），mitoKATP通道开放剂Diazoxide（Diaz）预处理组（E3组）；检测心脏功能恢复率、心肌含水量、血清肌酸激酶和乳酸脱氢酶漏出率、三磷酸腺苷（ATP）含量、超氧化物歧化酶活性、丙二醛含量、心肌细胞内Ca^2＋含量、心肌线粒体Ca^2＋含量、心肌线粒体Ca^2＋-三磷酸腺苷酶活性（Ca^2＋-ATPase）、心肌线粒体合成ATP的能力；电子显微镜观察心肌超微结构。结果E1组、E3组心功能恢复优于I／R组和E2组，心肌含水量低于I／R组和E2组（P〈0．05）；E1组、E3组三磷酸腺苷含量、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ATP的能力均优于I／R组和E2组（P〈0．05），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组、E2组（P〈0．05）；E1组、E3组心肌超微结构损伤较I／R组和E2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mitoKATP通道的开放起作用。

Objective To investigate the role of mitochondrial adenosine triphosphate-sensitive potassium channel （mitOKATP） in immature myocardial isehemic preconditioning, and to provide evidence for immature myocardial protection. Methods Langendorff isolated heart infused model was used in the experiment. Twenty-four rabbits （aged from 14 to 21 days） were randomly divided into 4 groups： ischemia-reperfusion group（I/R group）, myocardial ischemic preconditioning group（E1 group）, 5-hydroxydecanoate（5-HD） group （E2 group） and Diazoxide （Diaz） group （E3 group）. Hemodynamics recovery rate, myocardial water content（MWC）, the leakage rates of serum creatine kinase and lactate dehydrogenase, adenosine triphosphate content, superoxide dismutase activity, malondialdehyde content, myocardial cell Ca^2＋ content and myocardial mitochondriat Ca^2＋ content, myocardial mitochondrial Ca^2＋ - ATPase activity, the adenosine triphosphate（ATP） synthesizing ability of myocardial mitochondria were tested, and myocardial ultrastrueture was observed via electron microscopy. Results The hemodynamics recovery rate, myocardial water content （P 〈 0. 05）, adenosine triphosphate content, superoxide dismutase activity, myocardial mitoehondrial Ca^2＋ -adenosine triphosphyatase （ATPase） activity and the ATP synthesizing ability of myocardial mitoehondria of the rabbits in E1 and E3 group were significantly better than that in I/R group and E2 group（P〈 0.05）. Malondialdehyde content, the leakage rates of serum ereatine kinase and lactate dehydrogenase, myocardial cell Ca^2＋ content and myocardial mitochondrial Ca^2＋ content of the rabbits in E1 group and E3 group were significantly lower than that in I/R group and E2 group （P〈0.05）. The myocardial ultrastructure injury in E1 and E3 group were significantly reduced compared with that in I/R and E2 group. Conclusion Myocardial ischemic preconditioning has significant protective effects on immature myocardium. Its mechanism may be related to the activation of mitoKATP.