楸毒素抗E-4031所致豚鼠离体心脏和心肌细胞LQT2作用的研究

Effect of mallotoxin against LQT2 induced by E-4031 in isolated guinea pig hearts and cardiomyocytes

目的观察楸毒素(mallotoxin,MTX)对E-4031诱发豚鼠离体心脏和心肌细胞LQT2的作用。方法采用Langendorff逆行主动脉灌流法对豚鼠离体心脏进行灌流,采集离体心脏表面Ⅱ导联心电图以考察低、中、高3个浓度MTX及其在应用hERG通道阻断剂E-4031条件下,对QT/QTc间期、跨室壁离散度、电生理平衡指数的影响;酶解法分离豚鼠单个心室肌细胞,应用全细胞膜片钳技术分别在正常和hERG通道阻断剂E-4031存在条件下,记录低、中、高3个浓度的MTX对动作电位时程的影响。结果 MTX缩短豚鼠离体心脏QT间期,降低跨室壁离散度,减小电生理平衡指数。MTX可逆转E-4031诱发的QT间期延长、跨室壁离散度增加和电生理平衡指数增大。MTX缩短豚鼠心室肌细胞动作电位复极时程,降低APD90、APD60、APD30,加速复极。MTX可逆转E-4031诱发的动作电位复极时程延长。结论MTX缩短QT间期,降低复极跨室壁离散度,减小电生理平衡指数和缩短动作电位复极时程,具有抗E-4031所致LQT2的作用。

Aim To investigate the effect of mallotoxin （MTX） on LQT2 induced by E-4031 in isolated guinea pig hearts and ventricular myocytes. Methods The i-solated guinea pig heart underwent retrograde perfusion using Langendorff technique. In order to determine the effects of different concentrations of MTX on QT/QTc interval,transmural dispersion of repolarization（TDR） and index of cardiac electrophysiological bal-ance （iCEB） in the absence and presence of hERG channel blocker E-4031 , the electrocardiogram of iso-lated guinea pig hearts was recorded using Biopac physiological record. Single ventricular myocytes were isolated from guinea pig heart by enzymatic dissocia-tion. Effects of MTX on action potential duration （APD） in the absence and presence of E-4031 were recorded by current clamp mode using whole patch clamp technique. Results MTX shortened the QT in-terval, reduced TDR, and decreased iCEB in isolated guinea pig heart. MTX could reverse the prolongation of QT interal and the increased TDR induced by E- 4031. MTX shortened the action potential duration and decreased APD90 , APD60 and APD30 in isolated guinea pig ventricular myocytes. MTX could reverse the pro-longation of action potential repolarization duration in-duced by E -4031. Conclusion MTX shortens QT in-terval , decreases TDR , reduces iCEB , as well as shortens APD , thus reversing LQT2 induced by E- 4031.