重组人肿瘤坏死因子受体融合蛋白对大鼠急性心肌梗死室性心律失常的影响  

Efficacy of rhTNFR:Fc on ventricular arrhythmia in rats with acute myocardial infarction in vivo

作　　者：陈昱[1,2] 陈志坚[1] 廖玉华[1] 曹喆[1] 夏嘉鼎[1] 杨华[1] 杜以梅[1] 

机构地区：[1]华中科技大学协和医院心内科华中科技大学同济医学院心血管病研究所,武汉430022 [2]济宁医学院附属医院心内科,山东济宁272100

出　　处：《临床心血管病杂志》2009年第8期585-587,共3页Journal of Clinical Cardiology

基　　金：国家自然科学基金(No:30770880);国家973计划(No:2007CB512005)

摘　　要：目的:通过大鼠急性心肌梗死(AMI)模型探讨重组人肿瘤坏死因子受体融合蛋白(rhTNFR:Fc)对AMI室性心律失常发生的影响。方法:将240只大鼠随机分为假手术组(Sham组)、AMI组和rhTNFR:Fc组。Sham组开胸后不结扎冠状动脉;AMI组开胸后结扎冠状动脉左前降支(LAD),建立AMI模型;rhTNFR:Fc组结扎LAD前24h腹腔注射rhTNFR:Fc。于结扎前10min和结扎后10min、20min、30min、60min、3h、6h、12h,记录心电图,观测程序刺激诱发的室性心律失常;通过免疫组化法检测各时间点各组心肌TNF-α的表达水平。结果:AMI组和rhTNFR:Fc组结扎后10min即可诱发室性心律失常,30min内诱发性室性心律失常的发生最频繁,峰值在15～25min,以后逐渐减少,1h后很少能诱发;急性缺血心肌TNF-α分泌的时间窗规律与上述基本一致。rhTNFR:Fc组心肌检测出的TNF-α及室性心律失常发生次数均明显少于AMI组(P<0.05)。Sham组无明显变化。结论:rhTNFR:Fc能明显降低大鼠AMI室性心律失常的发生。Objective： To explore the efficacy of recombinant human tumor necosis factor-Fc fusion protein （rhTNFR：Fc） on ventricular arrhythmia induced by acute myocardial infarction in Rats in vivo. Method： Two hundred and forty rats randomized into sham operation group, acute myocardial infarction group and rhTNFR： Fc group. Anterior wall myocardial infarction was produced in AMI group by ligating the left anterior descending coronary artery, and it was not produced in sham operation group, while the rhTNFR： Fc group was treated with rhTNFR：Fc, a TNF-α sequestrant, 24 hours before LAD coronary artery ligation. ECG was observed and ventricular arrhythmias induced by programmed electrical stimulation were recorded at baseline, 10 min, 20 min, 30 min, 60 min, 3 h, 6 h and 12 h after ligation; while expression of TNF-α among different groups was detected by immunohistochemistry. Result：Ventricular arrhythmia appeared by 10 min after ligation, reached the climax at 10-- 30 min, with a peak incidence at 15--25 min, and recovered gradually then. The expression of TNF-α was in the similar way. Compared with the AMI group, there was less incidence of ventricular arrhythmias and TNF-α in the rhTNFR：Fc group, P〈0.05. Conclusion： rhTNFR： Fc could markedly reduce the incidence of ventricular arrhythmia in rats with AMI in vivo.

关 键 词：心肌梗死 肿瘤坏死因子-Α 室性心律失常 重组人肿瘤坏死因子受体融合蛋白 

分 类 号：R542.2[医药卫生—心血管疾病]