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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 investigate the effect of recombinant human tumor necrosis factor receptor fusion protein (rhTNFR: Fc) on ventricular arrhythmia in AMI rats by acute myocardial infarction (AMI) model. Methods: 240 rats were randomly divided into sham operation group (Sham group), AMI group and rhTNFR: Fc group. Sham group did not ligate the coronary arteries after thoracotomy; AMI model was established by thoracotomy in the AMI group; rhTNFR: Fc group was intraperitoneally injected with rhTNFR: Fc 24h before LAD ligation. The electrocardiogram was recorded 10 minutes before ligation and 10 minutes, 20 minutes, 30 minutes, 60 minutes, 3 hours, 6 hours and 12 hours after ligation. Ventricular arrhythmias induced by stimulation were observed. The levels of myocardial TNF-α in each group were detected by immunohistochemistry The expression level. Results: Ventricular arrhythmias were induced in AMI group and rhTNFR: Fc group at 10 minutes after ligation. Induced ventricular arrhythmia occurred most frequently within 30 minutes, peaked at 15-25 minutes, then decreased gradually and rarely induced after 1 hour. The time window of TNF-α secretion in acute ischemic myocardium was consistent with the above. The number of TNF-α and ventricular arrhythmia detected in myocardium of rhTNFR: Fc group was significantly less than that of AMI group (P <0.05). Sham group no significant change. Conclusion: rhTNFR: Fc can significantly reduce the occurrence of ventricular arrhythmia in AMI rats.