He Yan, Zeng Zhi-yu, Zhong Guo-qiang, Li Jin-yi, Li Wei-ke, Li Wei
Department of Cardiology, First Affiliated Hospital of Guangxi Medical University, Nanning 530021, China.
Zhonghua Xin Xue Guan Bing Za Zhi. 2010 Apr;38(4):357-62.
To investigate the roles of mitochondrial connexin43 (Cx43) and mitochondrial ATP sensitive potassium channe1 (mitoK(ATP)+) in the postconditioning protection for rabbits underwent myocardial ischemia/reperfusion injury.
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), ischemic reperfusion group (IR), ischemic postconditioning group (PC) and PC plus 5-HD, a specific mitoK(ATP)+ 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.
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 + 5HD [(34.2 +/- 3.9)%] groups (all P < 0.01). Degree of mitochondria 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.
Ischemic postconditioning protected the heart from I/R injury by improving mitochondrial ultrastructure and by attenuating I/R induced decrease of mitochondria Cx43 expression. The protective effects of postconditioning was partly mediated by activating mitoK(ATP)+ pathway.
探讨线粒体连接蛋白43（Cx43）和线粒体ATP敏感性钾通道（mitoK(ATP)+）在兔心肌缺血/再灌注损伤后适应保护中的作用。
在麻醉开胸兔中，结扎左冠状动脉前降支（LAD）30分钟，再灌注4小时，随机分为四组（每组n = 16）：假手术组（Sham）、缺血再灌注组（IR）、缺血后适应组（PC）和PC加5 - HD（一种特异性mitoK(ATP)+抑制剂，PC + 5 - HD）。再灌注4小时后处死兔子。分别在基线、缺血结束时以及再灌注2小时和4小时时记录心率和平均动脉压，并测定血浆肌酸激酶同工酶（CK - MB）和心肌肌钙蛋白I（cTnI）活性。实验结束时测定心肌梗死面积并在电子显微镜下观察线粒体结构。分离线粒体，通过蛋白质免疫印迹法测定线粒体Cx43的蛋白含量。
与IR组[（35.7±5.8）%]和PC + 5HD组[（34.2±3.9）%]相比，PC组[（19.1±3.9）%]的血浆CK - MB、cTnI活性和心肌梗死面积显著降低（均P < 0.01）。与IR组和PC + 5HD组相比，PC组线粒体损伤程度显著降低（均P < 0.01）。与假手术组相比，IR组和PC + 5 - HD组线粒体Cx43含量显著降低（均P < 0.05），而PC组恢复。
缺血后适应通过改善线粒体超微结构和减轻缺血/再灌注诱导的线粒体Cx43表达降低来保护心脏免受缺血/再灌注损伤。后适应的保护作用部分通过激活mitoK(ATP)+途径介导。
