Ischemic preconditioning-mediated restoration of membrane dystrophin during reperfusion correlates with protection against contraction-induced myocardial injury
Ischemic preconditioning-mediated restoration of membrane dystrophin during reperfusion correlates with protection against contraction-induced myocardial injury
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DOI：
10.1152/ajpheart.01140.2003
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发表时间：
2004-07-01
影响因子：
4.8
通讯作者：
Imamura, H
中科院分区：
文献类型：
--
作者：
Kido, M;Otani, H;Imamura, H
肌营养不良蛋白是一种完整的膜蛋白，参与心肌肌层膜的稳定。我们推测，缺血再灌注过程中肌营养不良蛋白的丢失是收缩力引起的心肌损伤的原因，缺血预处理（IPC）所提供的心脏保护与肌营养不良蛋白的保存有关。将分离的和灌注的大鼠心脏进行30分钟的全脑缺血，然后在使用或不使用收缩阻滞剂2,3-丁二酮单肟（BDM）的情况下再灌注。IPC采用全缺血前5min缺血和5min再灌注3个周期引入。在正常灌注的心脏中，肌营养不良蛋白仅分布在肌细胞膜中，但在缺血30分钟后重新分布到肌原纤维部分，并且在存在或不存在BDM的情况下，在再灌注期间从这两个隔室中消失。肌营养不良蛋白的缺失发生在BDM停药后肌细胞摄取膜不渗透性埃文斯蓝染料之前，并与肌酸激酶释放和挛缩的发生有关。虽然IPC没有改变缺血30min引起的肌营养不良蛋白的再分布，但它促进了再灌注时肌营养不良蛋白的恢复。此外，在膜肌营养不良蛋白完全恢复后停用BDM时，未观察到肌细胞坏死。这些结果表明，IPC介导的再灌注期间肌营养不良蛋白膜的恢复与对收缩力诱导的心肌损伤的保护相关，并表明IPC所赋予的心脏保护可以通过暂时阻断收缩活性而增强，直到再灌注期间肌营养不良蛋白膜恢复。
Dystrophin is an integral membrane protein involved in the stabilization of the sarcolemmal membrane in cardiac muscle. We hypothesized that the loss of membrane dystrophin during ischemia and reperfusion is responsible for contractile force-induced myocardial injury and that cardioprotection afforded by ischemic preconditioning (IPC) is related to the preservation of membrane dystrophin. Isolated and perfused rat hearts were subjected to 30 min of global ischemia, followed by reperfusion with or without the contractile blocker 2,3-butanedione monoxime (BDM). IPC was introduced by three cycles of 5-min ischemia and 5-min reperfusion before the global ischemia. Dystrophin was distributed exclusively in the membrane of myocytes in the normally perfused heart but was redistributed to the myofibril fraction after 30 min of ischemia and was lost from both of these compartments during reperfusion in the presence or absence of BDM. The loss of dystrophin preceded uptake of the membrane-impermeable Evans blue dye by myocytes that occurred after the withdrawal of BDM and was associated with creatine kinase release and the development of contracture. Although IPC did not alter the redistribution of membrane dystrophin induced by 30 min of ischemia, it facilitated the restoration of membrane dystrophin during reperfusion. Also, myocyte necrosis was not observed when BDM was withdrawn after complete restoration of membrane dystrophin. These results demonstrate that IPC-mediated restoration of membrane dystrophin during reperfusion correlates with protection against contractile force-induced myocardial injury and suggest that the cardioprotection conferred by IPC can be enhanced by the temporary blockade of contractile activity until restoration of membrane dystrophin during reperfusion.