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

作　　者：安梦瑶 李燕 孙凯 尹永强 孙涛[6] 娄建石 AN Mengyao;LI Yan;SUN Kai;YIN Yongqiang;SUN Tao;LOU Jianshi(Department of Pharmaceutical Engineering,School of Chemical Engineering and Technology,Tianjin University,Tianjin 300072,China;Tianjin Tiancheng New Drug Evaluation Research Co.,Ltd.,Tianjin 300462,China;People's Hospital of Wuqing,Tianjin 301700,China;Fuyang Hospital of Anhui Medical University,Fuyang 236000,China;Department of Pharmacology,College of Basic Medical Sciences,Tianjin Medical University,300070 Tianjin,China;State Key Laboratory of Medicinal Chemical Biology,Nankai University,Tianjin 300071,China)

机构地区：[1]天津大学化工学院制药工程系,天津300072 [2]天津天诚新药评价有限公司,天津300462 [3]天津市武清区人民医院,天津301700 [4]安徽医科大学附属阜阳医院,安徽阜阳236000 [5]天津医科大学基础医学院药理学系,天津300070 [6]南开大学药物化学生物学国家重点实验室,天津300071

出　　处：《药物评价研究》2021年第2期314-321,共8页Drug Evaluation Research

基　　金：国家自然科学基金面上项目(81373410)。

摘　　要：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.

关 键 词：长QT综合征 牛磺酸镁配合物 全细胞膜片钳技术 缓慢激活延迟整流外向钾通道 色原烷醇293B 

分 类 号：R926[医药卫生—药学]