Propofol limits rat myocardial ischemia and reperfusion injury with an associated reduction in apoptotic cell death in vivo
Propofol limits rat myocardial ischemia and reperfusion injury with an associated reduction in apoptotic cell death in vivo
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DOI：
10.1016/j.vph.2008.10.002
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发表时间：
2009-01-01
影响因子：
4
通讯作者：
Chang, Ki Churl
中科院分区：
文献类型：
--
作者：
Jin, Yong Chun;Kim, WooYeol;Chang, Ki Churl
异丙酚是一种作用迅速、持续时间短的静脉催眠麻醉诱导剂，常用于有心肌缺血/再灌注（I/R）损伤威胁的临床情况。本研究旨在探讨异丙酚对大鼠心肌I/R凋亡损伤的保护作用。冠脉左前降支（LAD）闭塞25 min，再灌注2 h或6 h，诱导心肌I/R损伤。通过Western blot分析（Bcl-2、Bax表达）、DNA链断裂、TUNEL分析和心肌caspase-3活性测定评估细胞凋亡。异丙酚通过改善左室舒张压和左室压一阶导数最大值（+dp/dt）的正、负极值，显著减小梗死面积，改善I/ r诱导的心肌收缩功能障碍。TUNEL分析和DNA阶梯实验证实，异丙酚可提高I/R大鼠心脏Bcl-2/Bax表达比，降低caspase-3活性，减少心肌凋亡。在一项体外研究中，异丙酚以剂量依赖的方式增加了葡萄糖氧化酶（GOX）诱导的H9c2细胞抗氧化应激的活力。这些数据表明，异丙酚限制了I/R损伤，并减少了体内凋亡细胞死亡。(c) 2008爱思唯尔公司版权所有。
Propofol, a rapidly acting, short duration, intravenous hypnotic anesthetic induction agent, is often used in clinical situations where myocardial ischemia/reperfusion (I/R) injury is a threat. The aim of the present study was to evaluate the protective effect of propofol on myocardial I/R injury in rat due to apoptosis. Myocardial I/R injury were induced by occluding the left anterior descending (LAD) coronary artery for 25 min followed by either 2 h or 6 h reperfusion. Apoptosis was evaluated by Western blot analysis (Bcl-2, Bax expression), DNA strand breaks, TUNEL analysis and measuring myocardial caspase-3 activity. Propofol significantly reduced infarct size and improved I/R-induced myocardial contractile dysfunction by improving left ventricular diastolic pressure and positive and negative maximal values of the first derivative (+dp/dt) of left ventricular pressure. Propofol increased Bcl-2/Bax expression ratio and decreased caspase-3 activity in I/R rat hearts, which resulted in reduction of myocardial apoptosis as evidenced by TUNEL analysis and DNA laddering experiments. In an in vitro study, propofol increased H9c2 cell viability against oxidative stress induced by glucose oxidase (GOX) in a dose-dependent manner. These data suggest propofol limits I/R injury with an associated reduction in apoptotic cell death in vivo. (c) 2008 Elsevier Inc. All rights reserved.