CAJ | 학술논문

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.
목적 연구종류배사인자α(TNF-α)대급성심기경사대서실성심률실상발생적영향.방법 장240지웅성Wistar대서수궤(수궤수자법)분위가수술조(Sham조)、급성심기경사조(AMI조)화TNF-α길항제-중조인종류배사인자수체융합단백조(rhTNFR:Fc조).Sham조개흉후불결찰관상동맥;AMI조개흉후결찰관상동맥좌전강지(LAD),건립급성심기경사모형;rhTNFR:Fc조결찰전24 h복강주사rhTNFR:Fc 10 mg/kg.우결찰전10 min화결찰후10 min,20 min,30 min,60 min,3 h,6 h,12 h,기록심전도,관측각조자발화정서전자격유발적실성심률실상;통과면역조화화실시형광정량PCR,검측각조결찰전후각시간점심기TNF-α단백화mRNA적표체수평.수거처리채용방차분석화직선상관분석.결과 AMI조화rhTNFR:Fc조LAD결찰10 min후심기TNF-α적단백급mRNA표체개시증다,20～30 min시체도고봉,연후축점하강.실성심률실상발우적시간창여TNF-α표체적시간창기본일치.여AMI조상비,rhTNFR:Fc조심기TNF-α단백표체급찬성심률실상발생솔균교저(P<0.05),단TNF-α mRNA무명현차이.Sham조정개실험과정중무명현변화.결론 대서급성심기경사시,심기표체적TNF-α능촉진실성심률실상적발생.
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.