Shojima Takahiro, Hayashida Nobuhiko, Nishi Akinori, Takagi Kazuyoshi, Hori Hidetugu, Yoshikawa Kazuhiro, Aoyagi Shigeaki
Department of Surgery, Kurume University, 67 Asahi-machi, Kurume 830-0011, Japan.
Eur J Cardiothorac Surg. 2006 Sep;30(3):472-9. doi: 10.1016/j.ejcts.2006.06.011. Epub 2006 Jul 21.
Dystrophin is an integral membrane protein that stabilizes the sarcolemmal membrane integrity, and its loss may be involved in the mechanism of ischemia and reperfusion injury. It has been reported that ischemic preconditioning is related to the preservation of membrane dystrophin during ischemia and reperfusion. Preconditioning with nicorandil, a mitochondrial K(ATP) channel opener, may attenuate the injury by preventing a disturbance in the level of this membrane-associated protein.
The isolated rat hearts were subjected to 60 min of cardioplegic arrest, followed by 60 min of reperfusion. The hearts were divided into the following three groups according to the drugs given before cardioplegic arrest. The control group received saline intravenously 30 min before heart isolation. The nicorandil group received nicorandil (0.3 mg/kg) intravenously 30 min before isolation. The 5-HD group received 5-hydroxydecanoate (1 mg/kg) intravenously, a mitochondrial K(ATP) channel blocker, 5 min before nicorandil administration. Cardiac function, myocardial metabolism, dystrophin distribution and protein levels of dystrophin were assessed before and after cardioplegic arrest.
The nicorandil group showed significantly better cardiac function and a significant reduction in creatine kinase release during reperfusion. After 60 min of cardioplegic arrest, dystrophin, which was distributed predominantly in the sarcolemmal membrane before ischemia, was translocated to the costameric cytoskeleton in all groups. During reperfusion, the level of membrane dystrophin remained decreased in the majority of cardiomyocytes in the control and 5-HD groups, whereas it was restored to nearly the baseline level in the nicorandil group. The immunoblot analysis supported this result.
Depletion of sarcolemmal membrane dystrophin occurred during cardioplegic arrest and reperfusion. Nicorandil preconditioning may attenuate ischemia and reperfusion injury by maintaining the membrane structural integrity.
肌营养不良蛋白是一种整合膜蛋白，可稳定肌膜的完整性，其缺失可能参与缺血再灌注损伤的机制。据报道，缺血预处理与缺血再灌注期间膜肌营养不良蛋白的保存有关。用线粒体K（ATP）通道开放剂尼可地尔进行预处理，可能通过防止这种膜相关蛋白水平的紊乱来减轻损伤。
将离体大鼠心脏进行60分钟的心搏停止，然后再灌注60分钟。根据心搏停止前给予的药物，将心脏分为以下三组。对照组在心脏分离前30分钟静脉注射生理盐水。尼可地尔组在分离前30分钟静脉注射尼可地尔（0.3mg/kg）。5-HD组在给予尼可地尔前5分钟静脉注射线粒体K（ATP）通道阻滞剂5-羟基癸酸（1mg/kg）。在心搏停止前后评估心脏功能、心肌代谢、肌营养不良蛋白分布及肌营养不良蛋白的蛋白水平。
尼可地尔组在再灌注期间显示出明显更好的心脏功能，肌酸激酶释放显著减少。心搏停止60分钟后，缺血前主要分布在肌膜的肌营养不良蛋白在所有组中均转移至肌原纤维相关细胞骨架。在再灌注期间，对照组和5-HD组的大多数心肌细胞中膜肌营养不良蛋白水平仍降低，而尼可地尔组则恢复至接近基线水平。免疫印迹分析支持了这一结果。
在心脏停搏和再灌注期间发生了肌膜肌营养不良蛋白的耗竭。尼可地尔预处理可能通过维持膜结构完整性减轻缺血再灌注损伤。
