庚醇预处理对兔缺血再灌注心肌凋亡和线粒体结构与功能的影响

Effect of heptanol pretreatment on apoptosis and structural changes of mitochondria of myocardium with IR injury in rabbits

目的探讨庚醇预处理对兔心肌缺血再灌注心肌凋亡和线粒体结构与功能的影响及可能机制。方法大白兔80只,随机分为假手术组、心肌缺血再灌注组(IR组)、缺血预处理组(IP组)、庚醇预处理组(HT组)以及庚醇预处理加5-HD干预组(5-HD组)。采用TUNEL法检测各组缺血心肌细胞凋亡,用透射电镜观察心肌细胞的超微结构改变,同时检测线粒体膜电位、Ca^(2+)、MDA、超氧化物歧化酶(SOD)浓度。结果假手术组心肌线粒体结构正常。与IR组和5-HD组比较,HT组和IP组心肌凋亡指数明显减少,心肌线粒体形态结构改变明显减轻(P<0.05);线粒体膜电位明显升高、Ca^(2+)浓度明显下降(P<0.05,P<0.01)。与IR组比较,IP组SOD浓度明显升高、MDA浓度明显下降(P<0.05)。结论庚醇可改善心肌凋亡以及保护心肌线粒体结构,其机制可能与线粒体ATP敏感性钾通道有关。

Objective To investigate the effects of heptanol pretreatment on apoptosis and structural and functional changes of mitochondria induced by myocardial isehemia-reperfusion（IR） injury in rabbits and potential mechanism. Methods Eighty rabbits were divided randomly into five groups ： sham operation group, ischemia-reperfusion group （group IR）, isehemic preconditioning group（group IP）,heptanol pretreatment group（group HT） and 5-hydroxydecanoate（5-HD） plus heptanol pretreatment group（group 5-HD）,with sixteen rabbits in each group. All rabbits in the five groups were sacrificed 4 h after reperfusion. The heart was quickly removed for observing the structure of mitoehondria and measurement of the apoptosis rate by TUNEL method. Ultrastructural changes of myoeardium were observed under electron microscope. Mitochondrial membrane potential, Ca^2＋ concentration, MDA content and SOD activity of myocardial mitochondria were examined. Results The structure of myocardial mitochondria in sham operated group was normal. Compared with group IR and group 5-HD,in group IP and group H T, the damage of mitochondrial ultrastructure was milder and the apoptosis rate was decreased,mitochondrial membrane potential was significantly higher and Ca^2＋ concentration was much lower （P 〈 0.05 ,P〈 0.01）. Compared with group IR,in group IP, MDA content was much lower and SOD activity was significantly higher （P 〈 0.05）. Conclusion Heptanol pretreatment can protect the heart from IR injury, the mechanism may be related to mitochondrial ATP sensitive potassium channel.