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.