TNF-α诱导连接蛋白重构在心肌梗死后室性心律失常发生中的作用  

The role of TNF-αon regulation of Cx43 and ventricular arrhythmias after myocardial infarction in rats

作　　者：杨华[1] 夏嘉鼎[2] 李欣[1] 许臣洪[1] 陈志坚[2] 

机构地区：[1]荆州市中心医院心内科,湖北荆州434020 [2]华中科技大学同济医学院协和医院心内科

出　　处：《临床心血管病杂志》2015年第10期1111-1115,共5页Journal of Clinical Cardiology

基　　金：国家973项目(No:2007CB512005);国家自然科学基金项目(No:30770880;30971242)

摘　　要：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。Objective：To investigate the effect of TNF-αon regulation of Cx43 and ventricular arrhythmias in rats after myocardial infarction.Method：Sixty male Wistar rats were randomly divided into three groups：MI group（n=20）,rhTNFR：Fc group（n=20）and Sham group（n=20）.Rats with MI were established by liquid nitrogen cryoinjury method.Programmed electrical stimulation was imposed on the hearts of the three groups to induce ventricular arrhythmia.Protein expression levels of TNF-αand Cx43 were detected by Western blot and the distribution of Cx43 was observed by laser scanning confocal on 30 days after myocardial infarction.Result：Compared with sham group,in MI group,the protein expression levels of TNF-αwere significantly increased（P0.05）;phoshporylated Cx43 protein levels were significantly decreased（P0.05）;nonphoshporylated Cx43 protein levels and the incidence of ventricular arrhythmias were higher（P0.05）.The location of Cx43 was distributed sparely at intercaleted disks in MI group.After MI rats were treated by rhTNFR：Fc,compared with MI group,the protein expression levels of TNF-αexpression significantly were reduced（P0.05）;phoshporylated Cx43 levels protein were higher and nonphoshporylated Cx43 levels were lower（P0.05）;the incidence of ventricular arrhythmias was decreased（P0.05）.In addtion,the abnormal distribution of Cx43 in rhTNFR：Fc group was reversed compared with MI group.Conclusion：Remodeling of Cx43 induced by TNF-αmay be an important role of ventricular arrhythmias in rats after myocardial infarction.

关 键 词：心肌梗死 肿瘤坏死因子-α 室性心律失常 缝隙连接蛋白43 激光共聚焦显微镜 

分 类 号：R541.7[医药卫生—心血管疾病]