心肌缺血晚期再灌注后的心肌损伤及其与核因子-κB的关系

Myocardial injury after late ischemia reperfusion and It’s relationship with nuclear factor-κB level in rabbit model

目的:研究心肌缺血晚期再灌注后的心肌损伤现象及其与核因子(NF)-κB的关系。方法:32只家兔随机分为4组(每组8只):假手术组(S组)、持续缺血组(I组)、晚期再灌注组(I/R组)、PDTC干预组(P组),建立体内心肌缺血再灌注动物模型。S组冠状动脉旷置6h,I组冠状动脉持续结扎6h,I/R组结扎冠状动脉3h后再灌注3h,P组结扎冠状动脉3h后再灌注3h,并于再灌注前10min静脉注入PDTC(200mg/kg)。6h后处死动物取心脏组织分别检测超氧化物歧化酶(SOD)、丙二醛(MDA)、谷胱甘肽还原酶(GR)含量,免疫组化指标NF-κB、IκBα,凋亡指数(AI)。结果:与S组相比,I/R组、P组和I组的SOD、GR降低,MDA、NF-κB、IκBα、AI升高;I/R组与I组相比,SOD、GR降低,MDA、NF-κB、IκBα、AI升高;P组与I/R组相比SOD、GR、IκBα升高,MDA、NF-κB、AI降低;差异均有统计学意义(P<0.05)。结论:心肌缺血晚期再灌注可导致梗死边缘区心肌细胞凋亡增加,提示存在再灌注损伤现象。氧化应激增强、NF-κB的过度激活可能是导致晚期再灌注损伤的重要因素。

Objective： To investigate myocardial injury after late ischemia reperfusion and it＇s relationship with NF-kB level in rabbit model. Method：Thirty-two adult rabbits were randomly divided into four groups： （S） sham; （Ⅰ） persistent ischemia; （I/R） late ischemia-reperfusion, consisting of 3 h of myocardial ischemia, followed by 3 h period of reperfusion; and （P） PDTC treatment before reperfusion. All animals were sacrificed at 6 hours after the beginning of the experiments. Border region of infarcted myocardium were incised for analyzing the concentration of SOD, MDA, GR and the expression of NF-kB, IkBα and the apoptosis index （AD Result：SOD, GR were lower and MDA, NF-kB, IkBa,AI were higher in I/ R,P and Ⅰ groups, compared with S group（P〈0.05）; SOD, GR were lower , MDA,NF-kB,IkBa,AI were higher in I/R group, compared with Ⅰ group（P〈0.05）; SOD, GR, IkBα were higher and MDA,NF-kB,AI were lower in P group, compared with I/R group（P〈0.05）. Conclusion： More apoptotic cardiomyocyte are detected in border region of infraction dium during late ischemia reperfusion than during persistente ischemia, which indicated the existence of late ischemia-reperfusion injury. Late ischemia-reperfusion injury seems be induced by over-activated NF-kB and enhanced oxidative stress.