【作者】 杨华；

【导师】 陈志坚；

【作者基本信息】 华中科技大学 ， 内科学， 2010， 硕士

【摘要】 第一部分TNF-α表达在大鼠心肌梗死后室性心律失常发生中的作用目的:探讨大鼠心肌梗死(MI)后TNF-α表达在室性心律失常发生中的作用。方法:采用液氮冷冻法建立大鼠MI模型。将60只雄性大鼠随机分为3组:心肌梗死组(MI组,n=20)、TNF-α螯合剂组(rhTNFR:Fc组, n=20)和假手术组(Sham组, n=20)。在MI模型建立30d后,运用程序电刺激方法,观察诱发室性心律失常的发生情况,同时用Western Blot和激光共聚焦显微镜检测TNF-α蛋白表达水平。结果:与假手术组比较,心梗组大鼠心肌组织TNF-α表达显著增加(P<0.05),室性心律失常诱发率亦明显增高(P<0.05);与心梗组比较,rhTNFR:Fc组大鼠心肌组织TNF-α表达显著减少(P<0.05),室性心律失常诱发率亦明显降低(P<0.05)。结论:心梗后大鼠心肌组织TNF-α表达明显增加,大量TNF-α表达与心梗后室性心律失常的发生密切相关。第二部分TNF-α对大鼠心肌梗死后Cx43重构的调节作用及其对室性心律失常发生的影响目的:研究TNF-α对大鼠心肌梗死后Cx43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MI模型。将60只雄性大鼠随机分为3组:心肌梗死组(MI组, n=20)、TNF-α螯合剂组(rhTNFR:Fc组, n=20)和假手术组(Sham组, n=20)。在MI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,用Western Blot检测TNF-α、Cx43磷酸化和非磷酸化的表达水平。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,心肌梗死组大鼠心肌组织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分布呈现显著异常;该组室性心律失常的诱发率明显增高(P<0.05)。与心梗组比较,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异常分布情况有所减轻;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,其在心梗后室性心律失常发生中可能发挥重要作用。更多还原

【Abstract】 PartⅠThe effect of TNF-αexpression on ventricular arrhythmias in rats after myocardial infarctionObjective:To study the effect of TNF-αexpression on ventricular arrhythmias in rats with myocardial infarction.Methods : 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 to induce ventricular arrhythmia 30 days after myocardial infarction. Protein expression levels of TNF-αwere detected by Western blot and laser scanning confocal 30 days after myocardial infarction.Results:Compared with sham group, the protein expression levels of TNF-αwere significantly increased and the incidence of ventricular arrhythmias was significantly higher in MI group (P <0.05). Compared with MI group, the protein expression levels of TNF-αexpression significantly were reduced and the incidence of ventricular arrhythmias was also significantly lower in rhTNFR:Fc group (P <0.05).Conclusion:There is relationship between TNF-αexpression and ventricular arrhythmias after MI in rats. PartⅡThe role of TNF-αon regulation of Cx43 and ventricular arrhythmias after myocardial infarction in ratsObjective: To investigate the effect of TNF-αon regulation of Cx43 and ventricular arrhythmias in rats after myocardial infarction.Methods: 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.Results:Compared with sham group, in MI group, the protein expression levels of TNF-αwere significantly increased(P<0.05); phoshporylated Cx43 protein levels were significantly decreased (P<0.05); nonphoshporylated Cx43 protein levels and the incidence of ventricular arrhythmias were higher (P<0.05). 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(P<0.05); phoshporylated Cx43 levels protein were higher and nonphoshporylated Cx43 levels were lower(P<0.05); the incidence of ventricular arrhythmias was decreased (P<0.05). 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.更多还原