二氮嗪对大鼠心肌缺血再灌注损伤影响.docVIP

二氮嗪对大鼠心肌缺血再灌注损伤影响 　 作者：沈诚，范士志，陈建明，李志平，李寒 【摘要】 目的研究二氮嗪(DZ)开放线粒体ATP敏感性钾通道对缺血再灌注损伤所致大鼠心肌组织ICAM-1和TNF- α表达的影响。方法采用离体工作心脏灌注模型,大鼠随机分为正常对照组，缺血再灌注组，DZ治疗组, DZ抑制剂-格列苯脲组。采用RT-PCR法测定心肌ICAM-1mRNA表达,ELISA检测试剂盒检测TNF- α蛋白含量。结果与正常对照组相比, 心肌组织ICAM-1表达和TNF- α含量在缺血再灌注后有显著性增加(Plt;0.01)。DZ处理后, ICAM-1表达和TNF- α含量与缺血再灌注组相比有明显下降(Plt;0.05); 格列苯脲组ICAM-1表达和TNF- α含量明显高于DZ治疗组(Plt;0.05)。结论心肌缺血再灌注损伤使ICAM-1和TNF- α表达明显升高, 二氮嗪(DZ)开放线粒体ATP敏感性钾通道可下调心肌组织ICAM-1和TNF- α的表达,这可能有助于减轻缺血再灌注所致心肌损伤。 　　 【关键词】 ATP敏感性钾通道；缺血再灌注； ICAM-1； TNF- α 　　The Effect of Diazoxide on Ischemia-Reperfusion Injury in Rat Cardiac Muscles 　　Abstract: OBJECTIVE To investigate the effect of diazoxide on expression of ICAM-1 and TNF- α during ischemia-reperfusion in rat cardiac muscles. METHODS Using isolated rat heart model, 40 male SD rats were randomly divided into normal control group(n=10), ischemia-reperfusion group(n=10), diazoxide treatment group(n=10)and diazoxide inhibitor group(n=10).The expression of ICAM-1mRNA was extracted and measured by RT-PCR. TNFα level in the myocardium were measured using enzyme-linked immunosorbent assay(ELISA) system. RESULTSThe expression of ICAM-1mRNA significantly increased after ischemia-reperfusion and TNF- α levels had the same change. treatment with diazoxide significantly inhibited the expression of ICAM-1mRNA, and concomitantly decreased the level of TNF- α in the myocardium. The diazoxide inhibitor can significantly increase the expression of ICAM-1mRNA and the level of TNF- α. CONCLUSIONThese data suggest that myocardial ischemia-reperfusion can result in intensive activation of ICAM-1 and TNF- α. Early treatment with diazoxide might be benefit for attenuation of myocardial injury induced by ischemia-reperfusion. 　　Key words：KATP; Ischemia-reperfusion; ICAM-1; TNF- α 　　心肌缺血再灌注损伤是阻碍缺血心肌从再灌注疗法中获得最佳疗效的主要原因。近年发现,肿瘤坏死因子(TNF- α)、细胞间粘附分子-1(ICAM-1)参与了心肌缺血再灌注损伤的发生发展,其作用越来越受到重视。心肌ATP敏感钾离子通道（ATP-sensitive potassium channel KATP）是心肌细胞内一种可被细胞内ATP和其他腺嘌呤核苷酸抑制的内向整流K+通道，可调节正常心肌细胞线粒体结构和功能。缺血再灌注损伤中，线粒体KAT