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目的:研究肿瘤坏死因子-α(TNF-α)对大鼠心肌梗死后连接蛋白(Cx)43重构调节作用及其对室性心律失常发生的影响。方法:采用液氮冷冻法建立大鼠心肌梗死模型。将60只雄性大鼠随机分为3组:心肌梗死组(MI组,20只)、TNF-α螯合剂组(rhTNFR:Fc组,20只)和假手术组(Sham组,20只)。在心肌梗死模型建立30d后,运用程序电刺激方法,观察室性心律失常的诱发情况,应用Western Blot检测TNF-α、Cx43磷酸化和非磷酸化的表达水平。采用激光共聚焦显微镜方法,观察TNF-α的表达、Cx43的分布情况。结果:与假手术组比较,MI组大鼠心肌组织TNF-α表达明显增加(P<0.05);Cx43磷酸化水平显著降低(P<0.05),而Cx43非磷酸化水平增加(P<0.05),Cx43分布呈现不均一分布;该组室性心律失常的诱发率明显增高(P<0.05)。与MI组比较,rhTNFR:Fc组大鼠心肌组织TNF-α表达显著减少(P<0.05);Cx43磷酸化水平表达增加(P<0.05),Cx43非磷酸化水平下降(P<0.05),而Cx43不均一分布有所减轻;室性心律失常的诱发率亦明显下降(P<0.05)。结论:心肌梗死发生后,TNF-α可以诱导Cx43表达和分布重构,其在心肌梗死后室性心律失常发生中可能发挥重要作用。
AIM: To investigate the regulatory effect of tumor necrosis factor-α (TNF-α) on the remodeling of connexin (Cx) 43 and its effect on ventricular arrhythmia in rats after myocardial infarction. Methods: Rat model of myocardial infarction was established by liquid nitrogen freezing method. Sixty male rats were randomly divided into three groups: MI group (n = 20), TNF-α chelator group (rhTNFR: Fc group, n = 20) and sham operation group (sham group, n = 20). Thirty days after establishment of myocardial infarction model, the induction of ventricular arrhythmia was observed by electrical stimulation. The expression of TNF-α, Cx43 phosphorylation and non-phosphorylation were detected by Western Blot. Laser confocal microscopy was used to observe the expression of TNF-α and the distribution of Cx43. Results: Compared with the sham operation group, the expression of TNF-α in MI group was significantly increased (P <0.05); the phosphorylation level of Cx43 was significantly decreased (P <0.05), while the non-phosphorylation level of Cx43 was increased , Cx43 distribution showed uneven distribution; induced evoked rate of ventricular arrhythmia was significantly higher (P <0.05). Compared with MI group, the TNF-αexpression of myocardial tissue in rhTNFR: Fc group was significantly decreased (P <0.05); Cx43 phosphorylation level was increased (P <0.05); Cx43 non-phosphorylation level was decreased (P <0.05) Cx43 heterogeneous distribution was reduced; induced rate of ventricular arrhythmia also significantly decreased (P <0.05). Conclusion: After myocardial infarction, TNF-α can induce Cx43 expression and distribution remodeling, which may play an important role in the occurrence of ventricular arrhythmia after myocardial infarction.