TNF-α早期表达在大鼠急性心肌梗死室性心律失常发生中的作用及机制研究  

The effect of TNF-α early expression on ventricular arrhythmias in rats with AMI and the study for mechanism

作　　者：肖华[1] 陈志坚[1] 廖玉华[1] 程翔[1] 刘坤[1] 王敏[1] 郭和平[1] 

机构地区：[1]华中科技大学同济医学院协和医院心内科,武汉430022

出　　处：《中国免疫学杂志》2008年第1期75-78,共4页Chinese Journal of Immunology

基　　金：国家"973"资助项目(2007CB512005);国家自然科学基金资助项目(30770880)

摘　　要：目的:通过大鼠急性心肌梗死(AMI)模型和离体心脏灌流模型探讨AMI后TNF-α早期表达在室性心律失常发生中的作用,并初步探讨其机制。方法:结扎大鼠左前降支,建立AMI模型,设手术组(MI组)和假手术组(S组)。分10、20、30、60分钟、3、6、12小时共7个时间点记录大鼠心电图。用实时荧光定量PCR法和免疫组化法检测AMI后各时间点TNF-α的mRNA和蛋白表达水平。大鼠离体心脏灌流模型观察TNF-α致室性心律失常的作用。激光共聚焦技术观察TNF-α对单个心肌细胞胞内钙浓度的影响。结果:与S组相比,MI组心肌组织中TNF-α从10分钟起mRNA和蛋白表达水平均出现表达明显升高(P<0.05)。MI组大鼠室性心律失常发生次数在各时间点均高于S组(P<0.05),并且与TNF-α分泌的时间窗重叠。200U/mlTNF-α灌流能够引起离体心脏室性心律失常,经2mg/kg依那西普(TNF-α受体螯合剂)预处理后同等浓度的TNF-α引起的室性心律失常较前明显地减少(P<0.05)。200U/ml的TNF-α可使大鼠心肌细胞胞内钙荧光强度短时间内增加121.0%±13.3%。结论:大鼠急性梗死后TNF-α表达与室性心律失常发生相关,其机制可能与TNF-α使心肌细胞胞内钙短时间内大量增加有关。Objective：To investigate the effect of TNF-α early expression on ventricular arrhythmias in rats with AMI and the mechanism. Methods：Rats with AMI were induced by left anterior descending coronary branch ligation. The mRNA and proteinum expression level of TNF-α were detected by real-time fluorescent quantitative PCR and histochemistry. Electrocardiogram was also recorded. Different concentrations of TNF-α were added to isolated rat hearts to observe the arrhythmia effects. The effect of TNF-α on intracellular Ca^2＋ concentration was detected by laser confocal technique. Results：The mRNA and protein expression levels of TNF-α were higher in MI group than in S group from 10 min after AMI（P 〈0. 05）. The frequency of ventricular arrhythmias was higher in MI group than in S group （ P 〈 0. 05 ） and the occurrence time of ventricular arrhythmias was coincided with the secretion of TNF-α. 200 U/ ml TNF-α could cause ventricular arrhythmias. Using etanercept beforehand, arrhythmias by TNF-α were reduced （ P 〈 0. 05 ）. TNF-α increased intracellular Ca^2＋ intensity. Conclusion：There is relationship between TNF-α early expression and ventricular arrhythmias in rats with AMI. The effect might be associated with the increased intracellular Ca^2＋ intensity caused by TNF-α.

关 键 词：心肌梗死 肿瘤坏死因子α 室性心律失常 离体心脏灌流 激光扫描共聚焦显微镜 

分 类 号：R541.7[医药卫生—心血管疾病]