心肌缺血-再灌注中核因子-kB活性变化及其对中性粒细胞黏附的影响

Activation Change of Nuclear Factor-kB and Influence on Adhesion of Polymorphonuclear Neutriphils in Myocardial Ischemic-reperfusion Injury

目的 研究心肌缺血 -再灌注时中性粒细胞 (PMN)内核因子 - k B(NF- k B)活性变化与 PMN细胞间黏附分子 (ICAM- 1)表达及其 PMN黏附的关系。 方法 新西兰白兔 2 4只 ,随机分为 3组 ,每组 8只。组 1:结扎兔左冠状动脉前降支造成心肌缺血 45分钟后再开放 ;组 2 :心肌缺血同组 1,用吡咯基二硫氨基甲酸酯 (PDTC)于心肌缺血前10分钟静脉注射 (15 mg/ kg) ;对照组 :不作动脉结扎。 3组分别于缺血前、再灌注 30分钟、6 0分钟、90分钟、12 0分钟、2 40分钟和 36 0分钟时用流式细胞仪检测 PMN ICAM- 1的表达 ,凝胶电泳迁移率分析检测 NF- k B的活性 ,测定PMN与脐静脉内皮细胞黏附率 (PMN- EC- 34 0 )。 结果 组 1中 PMN ICAM- 1的表达在心肌再灌注 12 0分钟时开始升高 ,并与 PMN- EC- 34 0黏附率变化有显著的相关性 ;NF- k B活性于心肌再灌注 30分钟后开始增高 ,12 0分钟达高峰 ,之后活性逐渐下降。组 2中 PMN ICAM- 1、NF- k B活化程度和 PMN- EC- 34 0黏附率升高幅度均低于组 1(P=0 .0 41,0 .0 2 9,0 .0 34 )。 结论 心肌缺血 -再灌注时刺激 NF- k B的活化 ,启动 PMN ICAM- 1的表达而参与缺血

Objective To study the relationship among the activation of nuclear factor kB(NF kB), expression of intercecullar adhesion molecule 1(ICAM 1) and adhesion rate of polymorphonuclear neutriphils EC 340(PMN EC 340) in myocardial ischemic reperfusion(IR). Methods Twenty four Newzeland rabbits were divided into three groups,8 rabbits each group.Group 1: rabbits were subjected to total occlusion 45min of left anterior desending artery(LAD) followed reperfusion, group 2: pyrrolidine dithiocarbamate(PDTC) 15mg/kg, pretreated rabbits 10 min before ischemia, contral group: rabbits were not subjected to occlusion of artery. The blood and ischemic myocardial samples were studied before ischemia ,30 min,60 min,90 min,120 min,240 min, and 360 min after ischemia reperfusion.The expression levels of ICAM 1 were evaluated by flow cytometry ,activation of NF kB by electrophoretic mobility shift assay(EMSA), the adhesion rate of PMN EC 340 were measured. Results In group 1, the expression levels of ICAM 1 were increased at 120 min and had positive correlation to the adhesion rate of PMN EC 340;activation of NF kB were increased significantly after IR 30 min and reached a peak at 120 min,then decreased. In group 2, the expression levels of ICAM 1, activation of NF kB and adhesion rate of PMN EC 340 were increased,but lower than that in group 1 ( P =0 041,0 029,0 034). Conclusion The inducible activation of NF kB starts up ICAM 1 expression of PMN and it is an important factor in myocardial IR injury.