异氟醚预处理对心肌缺血再灌注大鼠心肌ERK1/ERK2、HIF-1α和VEGF水平的影响  

Effects of isoflurane preconditioning on ERKI/ERK2, HIF-1αand VEGF in a rat model of myocardial ischemia reperfusion

作　　者：王琛[1] 谢红[1] 覃琴[1] 朱江[1] 徐府奇[1] 

机构地区：[1]苏州大学附属第二医院麻醉科,215004

出　　处：《中华麻醉学杂志》2007年第10期886-889,共4页Chinese Journal of Anesthesiology

基　　金：苏州大学创新团队资助项目（90134602）;志谢衷心感谢美国Medical College of Wisconsin麻醉系Dorothee Weihrauch,David A.Schwabe,Martin Bienengraeber,David C.Warltier,Judy R.Kersten,Phillip F.Pratt Jr.以及Paul S.Pagel提供的帮助和指导

摘　　要：目的探讨异氟醚预处理对心肌缺血再灌注大鼠心肌细胞外信号调节激酶（ERK1/ ERK2）、缺氧诱导因子-1α（HIF-1α）和血管内皮生长因子（VEGF）水平的影响。方法雄性Wistar大鼠90只,体重270～390 g。腹腔注射硫代仲丁巴比妥钠150 mg/kg麻醉后,阻断左冠状动脉前降支30 min。再灌注2 h。取60只大鼠,随机分为6组（n=10）,于缺血前CON组静脉注射0.9%生理盐水;PD组经3 min静脉注射ERK1/ERK2上游激酶抑制剂PD98059 1.0 mg/kg;DMSO组经3 min静脉注射PD98059溶媒DMSO 0.2 ml;ISO组吸入异氟醚1.0 MAC 30 min后停止吸入15 min;PD＋ISO组和ISO＋ PD组分别在吸入异氟醚前即刻和吸入异氟醚后即刻经3 min静脉注射PD98059 1.0 mg/kg。再灌注2 h后采用氯化硝基四氮唑蓝染色法测定心肌梗死面积。取剩余的30只大鼠,随机分为5组（n=6）,CON组、PD组、ISO组和PD＋ISO组所有处理同前,ISO正常对照组吸入异氟醚30 min后停止吸入165 min。再灌注2 h后,采用Western blot法测定ERK1/ERK2、HIF-1α和VEGF水平。结果与CON组比较,ISO组和ISO＋PD组心肌梗死区面积降低,ISO组和ISO正常对照组ERK1/ERK2、HIF-1α和VEGF水平升高（P〈0.05）;ISO正常对照组ERK1/ERK2水平高于ISO组（P〈0.05）。结论异氟醚预处理可通过上调心肌ERKI/ERK2、HIF-1α及VEGF的水平减轻大鼠心肌缺血再灌注损伤。　Objective To investigate the effects of isoflurane preconditioning on the expression of extracellular signal regulated kinase（ERK1/ERK2 ）,hypoxia inducible factor-1α（HIF-1α）and vascular endothelial growth factor（VEGF）in myocardium in a rat model of myocardial ischemia-reperfusion（I/R）.Methods Ninety male Wistar rats weighing 270-390 g were anesthetized with intraperitoneal thiobutabarbital 150 mg/kg, tracheostomized and mechanically ventilated.PaCO_2 was maintained at 25-40 mm Hg.Their chests were opened and hearts exposed.I/R was produced by reversible occlusion of left anterior descending branch（LAD）of coronary artery for 30 min followed by 2 h reperfusion.Sixty animals were randomly divided into 6 groups（n=10 each）： （1）control group received intravenous normal saline（NS）before I/R;（2）PD group received PD98059（ERKI/ ERK2 inhibitor）1.0 mg/kg iv before I/R;（3）DMSO group received DMSO（the PD98059 solvent）0.2 ml before I/R;（4）ISO group inhaled 1.0 MAC isoflurane for 30 min followed by 15 min wash-out before I/R;（5）PD＋ISO groupand（6）ISO＋PD group received PD98059 1.0 mg/kg before and after 30 min 1.0 MAC isoflurane inhalation.At the end of 2 h reperfusion the size of myocardial infarct was determined using triphenyl tetrazolium chloride staining.Another 30 animals were randomly divided into 5 groups（n=6 each）：（1）control group;（2） PD group;（3）ISO group;（4）ISO-control group inhaled 1.0 MAC isoflurane 30 min ＋ 165 min wash-out before I/R and（5）PD＋ISO group.At the end of 2 h reperfusion myocardial specimens were obtained for determination of expression of ERKI/ERK2,HIF-1αand VEGF proteins in myocardium（by Western blotting）.Results Preconditioning with isoflurane（group 4）and PD98059 after isoflurane（group 6）significantly reduced infarct size from 59%±4%（control group）to 41%±8%（ISO group）and 42%±9%（ISO＋PD group）respectively. The expression of ERKI/ERK2,H1F-1αand VEGF proteins was up-regulated

关 键 词：异氟醚 缺血预处理 心肌再灌注损伤 细胞外信号调节MAP激酶类 缺氧诱导因子1Α 血管内皮生长因子类 心肌 

分 类 号：R686[医药卫生—骨科学]