Xiao Hua, Chen Zhijian, Liao Yuhua, Cheng Xiang, Liu Kun, Wang Yanfu, Wang Min, Guo Heping
Laboratory of Cardiovascular Immunology, Institute of Cardiology, Union Hospital, Tong Ji Medical College, Hua Zhong University of Science and Technology, People's Republic of China.
Arch Med Res. 2008 Apr;39(3):285-91. doi: 10.1016/j.arcmed.2007.10.004.
Tumor necrosis factor-alpha (TNF-alpha) is found to play important roles in acute myocardial infarction (AMI). Ventricular arrhythmias arising from AMI are leading causes of sudden cardiac death (SCD). We sought to clarify the effect of TNF-alpha early expression on ventricular arrhythmias in rats with AMI and its mechanism.
Rats with AMI were induced by left anterior descending coronary branch ligation. The mRNA and protein levels of TNF-alpha in myocardium were detected by real-time fluorescent quantitative PCR, Western blotting and histochemistry. Meanwhile, electrocardiogram was recorded. Different concentrations of TNF-alpha were added to isolated rat hearts in isolated heart perfusions. Effect of TNF-alpha on intracellular Ca(2+) concentration was detected by laser confocal technique.
In AMI rats, mRNA and protein levels of TNF-alpha were higher than control (p <0.05), and the occurrence time of ventricular arrhythmias coincided with the secretion of TNF-alpha. TNF-alpha may cause ventricular arrhythmias in isolated rat heart perfusion models. Intracellular Ca(2+) intensity may quickly be increased by TNF-alpha.
Our results reveal the positive correlation between TNF-alpha early expression and ventricular arrhythmias in rats with AMI. This effect may be associated with the increased intracellular Ca(2+) intensity caused by TNF-alpha.
肿瘤坏死因子-α（TNF-α）在急性心肌梗死（AMI）中发挥重要作用。AMI引发的室性心律失常是心源性猝死（SCD）的主要原因。我们试图阐明TNF-α早期表达对AMI大鼠室性心律失常的影响及其机制。
通过结扎左冠状动脉前降支诱导大鼠发生AMI。采用实时荧光定量PCR、蛋白质印迹法和组织化学法检测心肌中TNF-α的mRNA和蛋白质水平。同时记录心电图。在离体心脏灌注实验中，向离体大鼠心脏加入不同浓度的TNF-α。采用激光共聚焦技术检测TNF-α对细胞内Ca(2+)浓度的影响。
在AMI大鼠中，TNF-α的mRNA和蛋白质水平高于对照组（p<0.05），室性心律失常的发生时间与TNF-α的分泌时间一致。TNF-α可能在离体大鼠心脏灌注模型中引发室性心律失常。TNF-α可使细胞内Ca(2+)强度迅速升高。
我们的研究结果揭示了TNF-α早期表达与AMI大鼠室性心律失常之间的正相关关系。这种作用可能与TNF-α导致的细胞内Ca(2+)强度增加有关。
