NF-κB在早期心肌缺血再灌流损伤中的作用  

The role of nuclear factor-κB at the early phase of myocardial ischemia-reperfusion injury

作　　者：张波[1] 王志农[1] 王军[1] 黄盛东[2] 刘延玲[2] 徐志云[1] 张宝仁[1] 

机构地区：[1]第二军医大学长海医院胸心外科,上海200433 [2]第二军医大学长海医院胸心外科研究所

出　　处：《中华急诊医学杂志》2005年第5期384-387,共4页Chinese Journal of Emergency Medicine

基　　金：上海市"曙光计划"资助项目(02SG30)

摘　　要：目的探讨核转录因子-κB(NF-κB)在心肌早期缺血再灌流损伤中的作用。方法将18只山羊随机分为单纯体外循环(CPB)组、缺血再灌流(IR)组、缺血再灌流加特异性NFκB抑制剂二硫代氨基甲酸吡咯烷(PDTC)组。建立山羊CPB模型,心脏行缺血60min,恢复血流再灌流90min,PDTC组在心肌缺血前应用PDTC(100mg kg)。于心肌再灌流后,测量血流动力学数据及测定局部心功能,并应用TUNEL染色检测心肌细胞凋亡数量,同时采用凝胶电泳迁移率改变分析(EMSA)法检测心肌组织中NFκB的含量。结果缺血再灌流能引起典型心肌缺血损伤的组织学改变,IR组NFκB在缺血心肌组织中大量激活,心肌组织中NFκB的活性水平显著高于CPB组(P>0.05);而PDTC组再灌流60、90min后,NF-κB的核转录活性明显减弱,显著低于IR组(P<0.05);原位末端标记表明,IR和PDTC组中心肌细胞凋亡指数分别为(11.2±0.4)%和(6.4±0.2)%,心肌损伤显著减轻(P<0.05)。结论核转录因子-κB在心肌早期缺血再灌流损伤中起重要作用,PDTC通过抑制NFκB的核转录活性,从而减轻了心肌缺血再灌流损伤。Objective To study the role of nuclear factor kappa B(NF_κB)at the early phase of myocardial ischemia_reperfusion injury.Methods Eighteen goats were randomly divided into three groups:merely extracorporeal circulation(CPB)group,ischemia reperfusion(IR)group,and ischemia reperfusion plus pyorrole dithitocarbamate(PDTC)group.The CPB models in goats were established.Hearts of goats were subjected to 60 minutes of ischemia and then 90 minutes of reperusion,and were administrated with PDTC before cardiac arrest in PDTC group.The hemodynamic data and cardiac function were measured.Cardiac myocyte apoptosis indexes were determined by Tdt-mediated dUTP nick end labeling,and NF_κB binding activity in the myocardium tissue was measured by electrophoretic mobility shift assay(EMSA)analysis.Results Ischemia_reperfusion caused typical myocardial ishcemic injury,while NF_κB was obviously activated during ischemic injury.NF_κB binding activity in the myocardium increased significantly compared with CPB group(P<0.05).However,after 60 minutes or 90 minutes of reperfusion,NF_κB binding activity and myocardial ischemic injury in PDTC group were reduced significantly.Apoptosis indexos of the ischemic myocardium of IR and PDTC groups were(11.2±0.4)% and(6.35±0.2),respectirely(P<0.05).Conclusion Nucler factor_κB plays an essential role at the early phase of myocardial ischemia-reperfusion injury.PDTC can reduce myocardial ischemia-reperfusion injury by preventing activation of transcription factor NF-κB.

关 键 词：缺血-再灌流损伤 早期 凝胶电泳迁移率改变分析 二硫代氨基甲酸吡咯烷 NF-κB抑制剂 核转录因子-κB 心肌细胞凋亡 心肌缺血损伤 缺血心肌组织 原位末端标记 细胞凋亡指数 转录活性 心肌再灌流 局部心功能 血流动力学 TUNEL 

分 类 号：R541[医药卫生—心血管疾病]