缺血后处理减轻心肌线粒体损伤对缝隙连接蛋白43的影响

目的观察缺血后处理对线粒体缝隙连接蛋白43(Cx43)的影响以及心肌保护的可能机制。方法健康新西兰大白兔64只.建立心肌缺血再灌注模型,随机分为4组,假手术组、缺血再灌注组、缺血预处理组、缺血后处理组,每组16只。检测各组心肌梗死面积,透射电镜观察心肌细胞的超微结构,荧光法检测线粒体膜电位,比色法检测线粒体Ca~(2+)和丙二醛浓度及超氧化物歧化酶(SOD)活性,Western blot法检测Cx43含量。结果与缺血再灌注组比较,缺血后处理组和缺血预处理组兔心肌梗死面积明显减少,心肌线粒体形态结构改变明显减轻,跨膜电位、SOD活性、线粒体Cx43明显升高,Ca~(2+)、丙二醛浓度明显降低(P<0.05,P<0.01)。与假手术组比较,缺血再灌注组兔线粒体Cx43明显下调(P<0.05)。结论缺血后处理保护心肌及线粒体可能与提高线粒体跨膜电位、降低线粒体氧自由基水平和减轻线粒体Ca~(2-)超载有关,其机制可能与提高线粒体Cx43表达有关。

Effect of ischemic postconditioning on injury and connexin Cx43 of mitochondria

Objective To observe the impact of ischemic postconditioning on mitochondrial connex-in 43(Cx43) and the possible mechanisms of myocardial protection.Methods Sixty-four rabbits were randomly divided into four groups with sixteen rabbits each:sham operation group,ischemia/ reperfusion group,ischemic preconditioning group and ischemic postconditioning group.All rabbits in the four groups were sacrificed 4 h after reperfusion.Myocardial infarct size and ultrastructural changes of mitochondria were observed,while membrane potential,Ca~(2+) concentration,MDA content and SOD activity of myocardial mitochondria were examined at the end of the experiment. The content of the mitochondria Cx43 was detected with Western Blot.Results Compared with ischemia/reperfusion group,myocardial infarct size was significantly reduced(P<0.01) and the damage of mitochondrial ultrastructure was lighter(P<0.05),Ca~(2+) concentration and MDA content were much lower,while membrane potential,SOD activity and mitochondria Cx43 expression were significantly higher(P <0.05) in ischemic preconditioning group and ischemic post-conditioning group(P <0.05).Compared with sham group,the mitochondria Cx43 expression in ischemia/reperfusion group was distinctly decreased.Conclusion Ischemic postconditioning can protect mitochondrial ultrastructure by increasing mitochondrial membrane potential and SOD activity, and also by alleviating Ca~(2+) overload and decreasing MDA content in myocardial mitochondria. The mechanism may be related to increasing expression of mitochondria Cx43.