核转录因子kappa B在山羊早期心肌缺血再灌注损伤中的作用研究  

Nuclear Factor-KB Plays an Essential Role in Early Phase of Myocardial Ischemia/Reperfusion Injury

作　　者：陈克彪[1] 王志农[1] 黄盛东[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,上海200433

出　　处：《实验动物与比较医学》2005年第4期203-207,共5页Laboratory Animal and Comparative Medicine

摘　　要：目的探讨核转录因子kappa B(NF—κB)在心肌早期缺血再灌注损伤中的作用。方法将 18只山羊随机分为单纯体外循环组(CPB组)、缺血再灌注组(IR组)、缺血再灌注加特异性NF- κB抑制剂(二硫代氨基甲酸吡咯烷,PDTC)组(PDTC组)。建立山羊CPB模型,心脏行缺血60 min, 恢复血流再灌注90 min,PDTC组在心肌缺血前应用PDTC(100 mg／kg)。于心肌再灌注后,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 EMSA法检测心肌组织中NF-κB的含量。结果缺血再灌注能引起典型心肌缺血损伤的组织学改变,IR组NF-κB在缺血心肌组织中大量激活,心肌组织中NF-κB的活性水平显著高于CPB组(P <0．05);而PDTC组再灌注60 min、90 min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6．35％± 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注损伤中起重要作用,PDTC通过抑制NF-κB的核转录活性,从而减轻了心肌缺血再灌注损伤。Objective To elucidate the role of nuclear factor kappa B （NF-kB） in early phase of myocardial ischemical reperfusion injury. Methods Eighteen goats were randomly divided into three groups： extracorporeal circulation group （CPB group）, ischemical reperfusion group （IR group） and ischemical reperfusion plus pyorrole dithitocarbamate group （PDTC, a special inhibitor of NF-kB activation）. Goat hearts were subjected to 60 minutes ofischemia, followed by 90 minutes of reperfusion（the inhibitor team goats were administered with PDTC before cardiac arrest）, then hemodynarnics of data and cardiac function was measured. Cardiomyocyte apoptosis index was determined by Tdt-mediated dUTP nick end labeling and NF-kB binding activity in the nucleus was measured by electrophoretic mobility shift assay （EMSA） analysis. Results Ischemia/reperfusion could lead to typical histological change of myocardial ischemic injury, while NF-kB was obviously activated in the ischemic injury. The levels of NF-kB binding activity in the myocardium increased signifficently in contrast to isolated extracorporeal circulation group （P〈0.05）. However, 60 minutes or 90 minutes after reperfusion, the levels of NF-kB binding activity in ischemic reperfusion with pyorrole dithitocarbamate group and the histological change of myocardial ischemic injury reduced significently. Apoptosis index of the ischemic myocardium from IR and PDTC groups was 11.2% ± 0.4% and 6.35% ±0.2% respectively （P〈0.05）. Conclusions Nuclear factor-kB plays an essential role in the early phase of myocardial ischemia/reperfusion injury, PDTC reduces myocardial ischemia/reperfusion injury by inhibiting activation of transcription factor NF-kB.

关 键 词：核转录因子-KB 心肌 再灌注损伤 

分 类 号：R363[医药卫生—病理学]