摘要
目的 研究肿瘤坏死因子α（TNF-α）对急性心肌梗死大鼠室性心律失常发生的影响.方法 将240只雄性Wistar大鼠随机（随机数字法）分为假手术组（Sham组）、急性心肌梗死组（AMI组）和TNF-α拮抗剂-重组人肿瘤坏死因子受体融合蛋白组（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）,建立急性心肌梗死模型;rhTNFR：Fc组结扎前24 h腹腔注射rhTNFR：Fc 10 mg/kg.于结扎前10 min和结扎后10 min,20 min,30 min,60 min,3 h,6 h,12 h,记录心电图,观测各组自发和程序电刺激诱发的室性心律失常;通过免疫组化和实时荧光定量PCR,检测各组结扎前后各时间点心肌TNF-α蛋白和mRNA的表达水平.数据处理采用方差分析和直线相关分析.结果 AMI组和rhTNFR：Fc组LAD结扎10 min后心肌TNF-α的蛋白及mRNA表达开始增多,20～30 min时达到高峰,然后逐渐下降.室性心律失常发牛的时间窗与TNF-α表达的时间窗基本一致.与AMI组相比,rhTNFR：Fc组心肌TNF-α蛋白表达及窜性心律失常发生率均较低（P〈0.05）,但TNF-α mRNA无明显差异.Sham组整个实验过程中无明显变化.结论 大鼠急性心肌梗死时,心肌表达的TNF-α能促进室性心律失常的发生.
Objective To explore the effects of tumor necrosis factor-α （TNF-α） on ventricular arrhythmias resulted from acute myocardial infarction （AMI） in rats. Method Two hundred and forty male Wistar rats were randomized （random number） into sham operation group, AMI group and recombinant human tumor necrosis factor receptor （rhTNFR） fusion protein （Fc） group. Acute anterior wall myocardial infarction was produced in rats of AMI group with ligating the left anterior descending coronary artery （LAD） , and the rats were just operated without ligation of LAD in sham group. The rats of Fc group were treated with rhTNFR-Fc （10 mg/kg）, a TNF-α antagonist, 24 hours before LAD ligation. The original ECG was recorded 10 min before ligation and the ECGs of ventricular arrhythmias occurred spontaneously or induced by programmed electrical stimulation were recorded 10 min, 20 min, 30 min, 60 min, 3 h, 6 h and 12 hours after ligation. The protein levels and mRNA expressions of TNF-α in rats in different groups were detected with histochemistry and real-time fluorescent quantitative PCR. Results The expressions of TNF-α mRNA and levels of TNF-α protein markedly increased 10 min after infarction, reached the climax 20-30 min later, and then gradually returned to the original level in AMI group and Fc group. The time-windows of spontaneous and induced ventricular arrhythmias were consistent with the time-window of expressions of TNF-α mRNA and levels of TNF-α protein. Compared with AMI group, there were lower levels of TNF-α protein and lower incidence of ventricular arrhythmias in Fc group （ P 〈 0.05） , but there was no significant difference in TNF-α mRNA between two groups. There was no obvious change in TNF-α in rats of sham operation group. Conclusions The expressions of TNF-α mRNA and levels of TNF-α protein induced by AMI could contribute the initiation of ventricular arrhythmias.
出处
《中华急诊医学杂志》
CAS
CSCD
北大核心
2010年第7期712-716,共5页
Chinese Journal of Emergency Medicine
基金
国家自然科学基金资助项目（30770880）
国家973计划资助项目（2007CB12005）
关键词
急性心肌梗死
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
Acute myocardial infarction
Tumor necrosis factor-α
Ventricular arrhythmia
Recombinant human tumor necrosis factor receptor：Fc fusion protein（rhTNFR： Fc）
