核因子kappaB在早期心肌缺血再灌注损伤中的作用  

The Role of nuclear factor-κB in the early phase of myocardial ischemia/reperf usion 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：《中华实验外科杂志》2004年第9期1042-1044,共3页Chinese Journal of Experimental Surgery

基　　金：上海市"曙光计划"资助项目(02SG30)

摘　　要：目的 探讨核因子(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(CPB)组、缺血再灌注(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。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,并应用脱氧核苷酸末端转移酶介导的缺口末端标记(TUNEL)法染色检测心肌细胞凋亡数量,同时采用凝胶电泳迁移率(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、90min后,NF-κB的核转录活性明显减弱,显著低于IR组(P<0.05);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NF-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-κB) in the early phase of myocardial ischemical reperfusion injury. Methods Eighteen goats were randomly divided into three groups:merely extracorporeal circulation group (CPB group), ischemical reperfusion group (IR group) and ischemical reperfusion plus pyorrole dithitocarbamate group (PDTC). Goat hearts were subjected to 60 min of ischemia, concomitantly 90 min of reperfusion (the inhibitor team goats were administered with PDTC before cardiac arrest), then hemodynamic data and cardiac function was measured. Cardiac my-ocyte apoptosis index was determined by Tdt-mediated dUTP nick end labeling and NF-κB binding activity in the nuclears was measured by electrophoretic mobility shift assay (EMSA) analysis. Results Ischemia/reperfusion could lead to typical histologic change of myocardial ischemic injury, while NF-κB was obviously activated in the ischemic injury. The levels of NF-icB binding activity in the myocardium was increased significantly in contrast to merely extracorporeal circulation group ( P < 0.05 ). However, after 60 min or 90 min reperfusion, the levels of NF-κB binding activity in ischemical reperfusion plus pyorrole dithitocarbamate group and the histologic change of myocardial ischemic injury was reduced significently. Apoptosis index of the ischemic myocardium from IR and PDTC groups detected by dt-mediated dUTP nick end labeling was11.2%±0.4% and6.35%±0.2% respectively (P < 0.05). Conclusion Nuclear factor-κB might play an essential role in the early phase of myocardial ischemia/reperfusion injury. PDTC reduces myocardial ischemia/reperfusion injury by preventing activation of transcription factor NF-κB.

关 键 词：NF-κB PDTC 核因子 缺血再灌注 CPB 血再灌注损伤 早期心肌缺血 转录活性 凝胶电泳 核苷酸 

分 类 号：R363[医药卫生—病理学]