Myocardial preservation specific for cardiomyocytes

目的：抗肌营养不良蛋白是一种膜蛋白，可保护肌膜免受物理应激引起的细胞胀亡。由于缺血预适应(IPC)在再灌流过程中保护线粒体并防止细胞胀亡，我们假设dystrophin是IPC保护线粒体远端的靶点。方法和结果：大鼠离体心缺血30min后再灌流。缺血5min，再灌流5min，共3个循环。在对照组和IPC心脏，缺血期间肌膜肌营养不良蛋白和心肌ATP的丢失是相似的。用线粒体呼吸解偶联剂2，4-二硝基酚(DNP)或线粒体F1F0-ATPase抑制剂寡霉素处理心脏时，心肌细胞膜肌营养不良蛋白和心肌细胞的ATP也有类似的丢失。然而，IPC心脏在再灌注期间增加了肌膜肌营养不良蛋白，同时增加了线粒体膜电位(Δψm)指标--四甲基罗丹明乙酯(TmRe)的摄取，增加了心肌细胞的ATP值，并抑制了心肌细胞的胀亡。DNP或寡霉素可抑制IPC介导的肌膜肌营养不良蛋白和三磷酸腺苷的再定位增加。此外，缺血的IPC心脏线粒体以DNP和寡霉素敏感的方式增加了dystrophin的重定位，与体外增加的ATP生成有关。结论：Dystrophin在再灌流过程中在肌膜上的重新定位增强可能是IPC介导的线粒体功能改善和再灌流时抗细胞胀亡之间的机制联系。

Objective : Dystrophin is a membrane protein that protects the sarcolemma from oncosis induced by physical stress. Because ischemic preconditioning (IPC) protects mitochondria and prevents oncosis during reperfusion, we hypothesized that dystrophin is a target of IPC distal to mitochondrial protection. Methods and Results : The isolated rat hearts were subjected to 30 minutes ischemia followed by reperfusion. IPC was introduced by 3 cycles of 5 minutes ischemia and 5 minutes reperfusion. The loss of sarcolemmal dystrophin and myocardial ATP during ischemia was similar in the control and the IPC heart. Similar loss of sarcolemmal dystrophin and myocardial ATP was observed when the heart was treated with 2,4-dinitrophenol (DNP), an uncoupler of mitochondrial respiration, or oligomycin, an inhibitor of mitochondrial F_1F_0-ATPase. However, the IPC heart increased sarcolemmal dystrophin during reperfusion associated with an increase in tetramethylrhodamine ethylester (TMRE) uptake, an indicator of mitochondrial membrane potential (Δψm), and myocardial ATP and inhibition of myocyte oncosis. The increase in relocalization of sarcolemmal dystrophin and myocardial ATP mediated by IPC was inhibited by treatment with DNP or oligomycin during reperfusion. Moreover, the ischemic IPC heart mitochondria increased relocalization of dystrophin from the insoluble to the soluble fractions associated with increased ATP generation in vitro in a DNP and oligomycin-sensitive manner. Conclusions : These results suggest that enhanced relocalization of dystrophin to the sarcolemma during reperfusion may be a mechanistic link between IPC-mediated improvement of mitochondrial function and its protection against oncosis upon reperfusion.