线粒体连接蛋白43参与缺血后处理对兔急性心肌缺血再灌注损伤的保护作用  

Mitochondrial connexin43 and postconditioning protection in rabbits underwent myocardial ischemia/reperfusion injury

作　　者：何燕[1] 曾志羽[1] 钟国强[1] 李金轶[2] 李伟科[2] 李薇[2] 

机构地区：[1]广西医科大学第一附属医院老年心内科,南宁530021 [2]广西医科大学第一附属医院心血管研究所

出　　处：《中华心血管病杂志》2010年第4期357-362,共6页Chinese Journal of Cardiology

基　　金：国家自然科学基金资助项目（30960131）;广西医疗卫生重点科研课题（桂卫重200848）;广西大型仪器协作共用网资助项目（635-2008-048）

摘　　要：目的探讨线粒体连接蛋白43（connexin43，Cx43）和线粒体ATP敏感性钾通道（mitoKATP^＋）在缺血后处理保护兔心肌缺血再灌注损伤中的作用。方法新西兰大白兔64只，建立心肌缺血再灌注模型，给予冠状动脉左前降支30min缺血，240min再灌注。随机分为4组，每组16只：假手术组、缺血再灌注组、缺血后处理组和5-羟葵酸加缺血后处理组。测定血浆磷酸肌酸激酶同工酶（CK—MB），肌钙蛋白I（cTnI）含量以及心肌梗死面积，采用电子显微镜观测心肌线粒体结构变化，Western blot检测线粒体Cx43蛋白表达。结果缺血后处理组心肌梗死面积为（19．1±3．9）％，明显低于缺血再灌注组（35．7±5．8）％，P〈0．01。再灌注4h末血浆CK—MB与cTnI活性，缺血后处理组明显低于缺血再灌注组和5-羟葵酸加缺血后处理组（P〈0．01）。与假手术组比较，其他各组线粒体均损伤明显（P均〈0．01）；缺血后处理组线粒体损伤程度轻于缺血再灌注组（P〈0．01）；缺血后处理组线粒体损伤程度明显轻于5-羟葵酸加缺血后处理组（P〈0．01）。缺血再灌注组和5．羟葵酸加缺血后处理组线粒体Cx43蛋白表达均显著低于假手术组（P均〈0．05）；缺血后处理组心肌线粒体Cx43蛋白表达明显高于缺血再灌注组（P〈0．05）；缺血后处理组心肌线粒体Cx43蛋白表达明显高于5-羟葵酸加缺血后处理组（P〈0．05）。结论线粒体Cx43可能参与了缺血后处理的心肌保护作用，其机制可能与mitoKATP^＋有关。Objective To investigate the roles of mitochondrial connexin43 （Cx43） and mitochondrial ATP sensitive potassium channel （mitoKATP^＋ ） in the posteonditioning protection for rabbits underwent myocardial ischemia/reperfusion injury. Methods In anesthetized open-chest rabbits, the left anterior descending artery （LAD） was occluded for 30 min and reperfused for 4 h and randomly divided into four groups （ n = 16 each ） ： sham operation group （ Sham ）, isehemic reperfusion group （ IR ）, ischemic postconditioning group （PC） and PC plus 5-HD, a specific mitOKATP inhibitor （PC ＋ 5-HD）. Rabbits were sacrificed post 4 h reperfusion. Heart rate and the mean arterial pressure were recorded and plasma CK-MB and cTnI activity were measured at baseline, at the end of ischemia, and after 2 h and 4 h of reperfusion, respectively. Myocardial infarct size was determined and mitochondria structure was observed under electron microscope at the end of the experiment. Mitochondria were isolated and the protein content of the mitochondrial Cx43 was determined by Western blot. Results Plasma CK-MB, cTnI activity and myocardial infarct size were significantly reduced in PC [ （ 19. 1 ± 3.9 ） % ] group compared to IR [ （ 35.7 ± 5.8 ） % ] and PC ＋ 5 HD [ （ 34. 2 ± 3.9） % ] groups （ all P 〈 0. 01 ）. Degree of mitoehondrla damage was significantly reduced in PC group compared to IR and PC ＋ 5HD groups （ all P 〈 0. 01 ）. The mitochondria Cx43 content was significantly decreased in IR group and PC ＋ 5-HD group compared to sham group （ all P 〈 0.05 ） and restored in PC group. Conclusion Ischemic postconditioning protected the heart from I/R injury by improving mitochondrial uhrastrueture and by attenuating I/R induced decrease of mitochondria Cx43 expression. The protective effects of postconditioning was partly mediated by activating mitoKATP pathway.

关 键 词：心肌再灌注损伤 线粒体 连接蛋白43 缺血后处理 

分 类 号：R363[医药卫生—病理学]