牛磺酸镁配合物对获得性长QT综合征亚型8模型下L型钙通道作用研究  

Effects of Taurine-Magnesium Coordination Compound on L-type calcium current in model of type 8 long QT syndrome

作　　者：安梦瑶 葛鹏 滕晋莹 娄建石 AN Mengyao;GE Peng;TENG Jinying;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;Department of Pharmacology,College of Basic Medical Sciences,Tianjin Medical University,300070 Tianjin,China)

机构地区：[1]天津大学化工学院制药工程,天津300072 [2]天津天诚新药评价有限公司,天津300462 [3]天津医科大学基础医学院药理学系,天津300070

出　　处：《药物评价研究》2021年第2期322-328,共7页Drug Evaluation Research

基　　金：天津市教委科研计划项目(2017KJ224)。

摘　　要：目的观察不同浓度牛磺酸镁配合物(TMCC)对获得性长QT综合征亚型8的抗心律失常机制。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CACNA1C基因的HEK293细胞模型。Bay K 8644(10 nmol/L)用来建立LQT8模型,采用全细胞膜片钳技术记录TMCC(0.01、0.10、1.00 mol/L)对对照和LQT8模型下HEK293细胞L型钙通道(LTCC)电流、豚鼠心室肌细胞动作电位的影响。结果在HEK293细胞细胞中,与对照组比较,0.1、1 mol/L TMCC组ICa,L电流密度显著减弱,差异有统计学意义(P<0.05、0.01)。与对照组比较,Bay K 8644组ICa,L的电流-电压(I-V)曲线显著下移,电流密度显著增强(P<0.01),使半数激活电压明显升高3.23倍,激活曲线左移,激活加快。TMCC(0.01、0.1、1 mol/L)可明显减弱Bay K 8644对ICa,L电流的增强作用,使下移的I-V曲线上移,0.1、1 mol/L浓度组差异有统计学意义(P<0.05、0.01);TMCC各浓度组均明显降低半数激活电压(P<0.05、0.01),恢复左移的激活曲线,使激活减慢。在豚鼠心室肌细胞中,与对照组比较,Bay K 8644显著延长30%、50%和90%复极化动作电位持续时间(APD30、APD50和APD90)(P<0.01);0.01、0.1、1 mmol/L TMCC均可以减弱Bay K 8644对APD30、APD50和APD90的延长作用,0.1、1 mmol/L浓度组差异显著(P<0.05、0.01)。结论TMCC通过缩短动作电位时程,减弱被增强的ICa,L电流,发挥一定的抗LQT8的作用。Objective In this study,the anti-arrhythmic effect of Taurine-Magnesium Coordination Compound(TMCC)was assessed on the model of type 8 long QT syndrome(LQT8).Methods Bay K 8644(10 nmol/L)was used to establish the LQT8 model in guinea pig ventricular myocytes and to enhance HEK293 cells stably expressing ICa,Lchannels.All cells were incubated for 24 h in the absence and presence of drugs.The ICa,Lcurrent and action potentials were recorded by using the whole-cell patch-clamp technique.Results In HEK293 cells,compared with control group,the ICa,Lcurrent density of TMCC 0.1 and 1 mol/L groups was significantly decreased(P<0.05 and 0.01).Compared with control group,the current voltage(I-V)curve of ICa,Lin Bay K 8644group decreased significantly,the current density increased significantly(P<0.01),the half activation voltage increased 3.23 times,the activation curve shifted to the left,and the activation accelerated.TMCC(0.01,0.1,1 mol/L)significantly reduced the enhancement of ICa,Lcurrent by Bay K 8644,and made the downward I-V curve move up,with significant difference between 0.1,1mol/L concentration groups(P<0.05 and 0.01).All TMCC concentration groups significantly reduced the half activation voltage(P<0.05 and 0.01),restored the left activation curve,and slowed down the activation.In guinea pig ventricular myocytes,Bay K8644 significantly prolonged the duration of repolarization action potential(APD30,APD50and APD90)compared with control group(P<0.01).0.01,0.1 and 1 mmol/L TMCC could attenuate the prolongation of APD30,APD50and APD90by BayK 8644,with significant differences between 0.1 and 1 mmol/L TMCC groups(P<0.05 and 0.01).Conclusion It was suggested that TMCC have anti-arrhythmic effect on LQT8 through shortening the action potential duration and inhibiting the increased ICa,Lcurrent.

关 键 词：长QT综合征 牛磺酸镁配合物 全细胞膜片钳技术 L型钙通道 Bay-K 8644 心律失常 

分 类 号：R965[医药卫生—药理学]