Reactive Oxygen Species-Induced Stimulation of 5′ AMP-Activated Protein Kinase Mediates Sevoflurane-Induced Cardioprotection
Reactive Oxygen Species-Induced Stimulation of 5′ AMP-Activated Protein Kinase Mediates Sevoflurane-Induced Cardioprotection
复制标题
DOI：
10.1161/circulationaha.108.828426
复制
发表时间：
2009-09-15
期刊：
影响因子：
37.8
通讯作者：
Bouwman, R. Arthur
中科院分区：
文献类型：
--
作者：
Lamberts, Regis R.;Onderwater, Geert;Bouwman, R. Arthur
背景-5'腺苷酸活化蛋白激酶（AMPK），一种众所周知的细胞能量状态调节剂，也参与缺血预处理导致的心脏保护作用。我们假设AMPK参与麻醉诱导的心脏保护，这种激活是由活性氧（ROS）介导的。方法和结果-隔离Langendorff灌注大鼠心脏进行35分钟的全脑缺血（I），然后再灌注120分钟（I/R）。心脏被分配到对照组（Con）或七氟醚组（Sevo），在I/R前接受3次5分钟的七氟醚（2.5vol%）。Western blot分析AMPK和内皮型一氧化氮合酶（eNOS）的磷酸化。在I/R后从左心室压力恢复和梗死面积（氯化三苯基四唑染色）评估心肌保护。在对照组中，缺血导致AMPK磷酸化水平增加2倍（Con 0.13 +/- 0.01 vs Con-I 0.28 +/- 0.05，P
Background-5' AMP-activated protein kinase (AMPK), a well-known regulator of cellular energy status, is also implicated in ischemic preconditioning leading to cardioprotection. We hypothesized that AMPK is involved in anesthetic-induced cardioprotection and that this activation is mediated by reactive oxygen species (ROS).Methods and Results-Isolated Langendorff-perfused rat hearts were subjected to 35 minutes of global ischemia (I) followed by 120 minutes of reperfusion (I/R). Hearts were assigned to a control group (Con) or a sevoflurane (Sevo) group receiving 3 times 5-minute episodes of sevoflurane (2.5vol%) before I/R. Phosphorylation of both AMPK and endothelial nitric oxide synthase (eNOS) were determined by Western blot analysis. Cardioprotection was assessed after I/R from recovery of left ventricular pressure and from infarct size (triphenyltetrazolium chloride staining). In the control group, ischemia resulted in a 2-fold increase in phosphorylation levels of AMPK (Con 0.13 +/- 0.01 versus Con-I 0.28 +/- 0.05, P