牛磺酸镁配合物对获得性长QT综合征模型的抗心律失常作用研究

Anti-arrhythmic effect of Taurine-Magnesium Coordination Compound on model of long QT syndrome

目的研究牛磺酸镁配合物(TMCC)对获得性长QT综合征(LQTS)模型的抗心律失常作用及作用机制。方法采用Langendorff逆行主动脉灌流酶解法,急性分离获得豚鼠单个心室肌细胞;建立表达KCNQ1/KCNE1基因的HEK293细胞模型。色原烷醇293B(5μmol/L)用来建立LQTS模型,采用全细胞膜片钳技术记录TMCC(0.01、0.10、1.00 mmol/L)对正常和LQTS模型豚鼠心室肌细胞动作电位和缓慢激活延迟整流外向钾通道(IKs)电流的影响。结果色原烷醇293B可以显著延长50%和90%复极化动作电位持续时间(APD50和APD90),0.01、0.10、1.00 mmol/L TMCC可以显著减弱色原烷醇293B延长APD50和APD90的作用(P<0.05、0.01)。TMCC(0.01、0.10、1.00 mmol/L)对抗色原烷醇293B对IKs电流的抑制作用,减弱色原烷醇293B对I-V曲线的下移,0.1、1.0 mmol/L浓度组显著减弱色原烷醇293B对IKs电流的抑制作用(P<0.01),呈现对抗LQTS的作用。结论TMCC通过缩短动作电位复极时程,增大被抑制的IKs电流,发挥一定的抗LQTS的作用。

objective The anti-arrhythmic effect of Taurine-Magnesium Coordination Compound(TMCC)was assessed on the model of long QT syndrome(LQTS).Methods Chromanol 293B(5μmol/L)was used to establish the LQTS model in guinea pig ventricular myocytes and to inhibit HEK293 cells stably expressing IKschannels.All cells were incubated for 24 h in the absence and presence of drugs.The IKscurrent and action potentials were recorded by using the whole-cell patch-clamp technique.Results Chromanol 293B significantly prolonged APD50and APD90(P<0.01).TMCC could attenuate the effect of chromanol 293B on prolongation APD50and APD90,which could be reversed significantly by TMCC(0.01,0.1,1.0 mmol/L)(P<0.05 and 0.01).TMCC(0.01,0.1,and 1 mmol/L)were concentration-dependently against the effect of chromanol 293B on IKscurrent inhibition.The IKsI-V curve was shifted downwards by chromanol 293B(5μmol/L),while upwards by TMCC.TMCC(0.01,0.10,and 1.00 mmol/L)could restore the decrease of peak IKsdue to chromanol 293B(P<0.01).Conclusion It was suggested that TMCC have antiarrhythmic effect on LQTS through shortening the action potential duration and increasing the inhibited IKscurrent.