氙气诱导晚期在体心脏预适应：环氧化酶2的作用  

作　　者：Nina C. Weber Jan Fraβdorf Christoph Ratajczak Yvonne Grueber Wolfgang Schlack Markus W. Hollmann Benedikt Preckel 吴镜湘(译) 徐美英(校) 

机构地区：[1]Laboratory of Experimental Intensive Care and Anesthesiology (L.E.I.C.A.), Academic Medical Center (A.M.C.), University of Amsterdam, Amsterdam, The Netherlands [2]Department of Anesthesiology, University Hospital, Dusseldorf, Germany [3]不详

出　　处：《麻醉与镇痛》2009年第6期29-36,共8页Anesthesia & Analgesia

摘　　要：背景氙气可诱导大鼠在体心脏的早期心肌预适应，但是否可诱导晚期心肌保护尚不知。环氧化酶2（COX-2）是介导心肌晚期缺血预适应（i-LPC）信号传导的重要介质之一。本文研究氙气是否可诱导晚期预适应（Xe—LPC）以及COX-2活性或表达是否介导了这种作用。方法雄性Wistar大鼠麻醉后置入冠状动脉阻断器。7天后动物随机分配到5个组，每组8只。i-LPC组通过阻断冠状动脉5分钟来诱发；Xe-LPC组通过吸入70％的氙气15分钟获得。其他大鼠用COX-2抑制剂NS-398（5mg·kg^-1，腹腔内注射）预处理，然后分别使用或不使用Xe-LPC。假手术组的动物不接受缺血预处理或氙气预处理，作为对照组。24小时后所有动物麻醉，收紧冠状动脉阻断器造成心肌缺血25分钟，继而开放再灌注2小时。TTC染色法测定心肌梗死面积。另外还在预处理后不同时间点取心脏，分别用PCR和Westernblot法检测COX-2mRNA及其蛋白表达。结果与对照组相比，缺血预处理组和氙气预处理组均可减少心肌梗死面积（所占百分比分别为：i-LPC组29％±7％，Xe—LPC31％±8％，与对照组比P均〈0．05，对照组为64％±6％）。NS-398可消除氙气诱导的心脏保护作用（该组为61％±6％，与Xe-LPC组比P〈0．05）。COX-2mRNA及其蛋白表达只在i-LPC组有所增加，Xe-LPC组无明显变化。结论氙气诱导晚期心肌预适应，这种作用可以被COX-2抑制剂消除，与缺血预适应相比，氙气诱导的预适应并不增加COX-2mRNA及其蛋白的表达。这一结果表明缺血预适应与氙气诱导的预适应在COX-2调节上存在差别。BACKGROUND： Xenon induces early myocardial preconditioning of the rat heart in vivo, but whether xenon induces late cardioprotection is not known. Cyclooxygenase-2 （COX-2） has been shown to be an important mediator in the signal transduction of myocardial ischemic late preconditioning （i-LPC）. We investigated whether xenon induces late preconditioning （Xe-LPC） and whether COX-2 activity and/or expression are involved in mediating this effect. METHODS： Anesthetized male Wistar rats were instrumented with a coronary artery occluder. After 7 d of recovery, animals were randomized to 1 of 5 groups each containing 8 animals. The i-LPC group underwent 5 min of coronary occlusion to induce i-LPC. Xe-LPC was achieved by administration of xenon （70 volume%） for 15 min. Additional rats were pretreated with the COX-2 inhibitor NS-398 （5 mg · kg^-1 body weight i. p.） with and without Xe-LPC. A group of sham operated animals not undergoing i-LPC or Xe-LPC served as controls （Con）. After 24 h, all animals were anesthetized and underwent 25 min of myocardial ischemia induced by tightening of the coronary artery occluder followed by 2 h of reperfusion. Myocardial infarct size was assessed by triphenyltetrazolium chloride staining. In additional experiments, hearts were excised at different time points after preconditioning to investigate COX-2 mRNA and protein expression by polymerase chain reaction and infrared Western blot, respectively. RESULTS： Both i-LPC and Xe-LPC reduced myocardial infarct size （% of the area at risk） compared with Con （i-LPC： 29±7%; Xe-LPC 31 ±8%, both P 〈 0.05 vs Con 64 ±6%）. NS- 398 abolished the cardioprotective effect of Xe-LPC （61 ±6%, P 〈0.05 vs Xe-LPC）. COX-2 mRNA and protein expression was only increased in the i-LPC group, but not in the Xe-LPC group. CONCLUSIONS： Xenon induces late myocardial preconditioning that is abolished by functional blockade of COX-2 activity. In contrast to i-LPC, Xe-LPC did not lead to an increased expression of CO

关 键 词：心肌预适应 晚期预适应 环氧化酶2 在体心脏 氙气 COX-2mRNA COX-2抑制剂 WESTERNBLOT法 

分 类 号：R542.2[医药卫生—心血管疾病] R331.31[医药卫生—内科学]