中文摘要：

目的：检测TNF-α对离体心肌组织块单相动作电位时程（MAPD）及离子通道电流的影响,初步探讨心梗后TNF-α诱导电生理异质性致室性心律失常发生的可能机制。方法：在离体大鼠心脏灌流的条件下,分离心肌组织块,电生理实验技术记录在不同浓度TNF-α灌流条件下的MAPD。用酶解法分离大鼠的心室肌细胞,应用膜片钳全细胞技术记录不同浓度TNF-α对单个心室肌细胞Ito和IK1的影响。结果：与对照组相比较,离体心肌组织块心内膜和心外膜MAPD浓度依赖性地随着TNF-α浓度的增加而增大（P〈0.05）;相同浓度TNF-α对心内膜和心外膜MAPD有不同的影响,尤其显著延长了心内膜的MAPD。经依那西普（TNF-α受体螯合剂）预处理后,相同浓度TNF-α对心内膜和心外膜MAPD影响不同导致的差异显著降低（P〈0.05）。将TNF-α作用于大鼠心室肌细胞,与对照组相比较,Ito和IK1电流密度随着TNF-α浓度的增加而降低（P〈0.05）。结论：TNF-α对心内膜及心外膜单相动作电位的不同影响可能对急性心梗后室性心律失常的形成有诱导或促进作用,其机制可能与TNF-α浓度依赖性抑制Ito和IK1电流,引起动作电位复极化异常从而诱发折返性心律失常有关。

英文摘要：

Objective：To explore the relationship between expression of tumor necrosis factor-α（TNF-α）and electrophysiological heterogeneity in isolated heart tissues and isolated rat ventricular myocytes. The arrhythmogenic mechanisms of TNF-α were further studied. Methods： Langendorff perfused heart tissues models were used to verify the arrhythmogenic effects of TNF-α. The monophasic action potentials（ MAPs） of the endocardium and epicardium from the isolated heart tissues were recorded by electrophysiological experiments. The isolated rat ventricular myocytes were obtained by enzymatic dissociation. K＋currents（ Ito,IK1） were recorded by using whole cell patch clamp technique. Results： Compared to the control group,the difference in MAPD between endocardium and epicardium dramatically increased with TNF-α（ P〈0. 05）. TNF-α could cause MAP duration（ MAPD） prolongation,and a single dose of TNF-αdifferentially affected the MAPs of endocardium and epicardium of isolated heart tissues. Compared to the control group,the K＋currents（Ito,IK1）were dose-dependently decreased with TNF-α in rat ventricular myocytes（P〈0. 05）. However,etanercept had no effects on the MAPD in the absence of TNF-α. Conclusion： TNF-α-induced heterogeneity of MAPD between the endocardium and epicardium may provide the substrate for the onset of ventricular arrhythmias during acute myocardial infarction. The effect might be associated with TNF-α contribute to re-entrant ventricular arrhythmias which resulted from decreased K＋currents（ Ito,IK1）.