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。BayK 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I_Ca，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，BayK 8644组I_Ca，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BayK 8644对I_Ca，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，BayK 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BayK 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I_Ca，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 BayK 8644 (10 nmol/L) was used to establish the LQT8 model in guinea pig ventricular myocytes and to enhance HEK293 cells stably expressing ICa,L channels. All cells were incubated for 24 h in the absence and presence of drugs. The I_{Ca, L} current and action potentials were recorded by using the whole-cell patch-clamp technique. Results In HEK293 cells, compared with control group, the I_{Ca, L} current 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 I_{Ca, L} in BayK 8644 group 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 I_{Ca, L} current by BayK 8644, and made the downward I-V curve move up, with significant difference between 0.1, 1 mol/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, BayK 8644 significantly prolonged the duration of repolarization action potential (APD30, APD50 and APD90) compared with control group (P<0.01). 0.01, 0.1 and 1 mmol/L TMCC could attenuate the prolongation of APD30, APD50 and APD90 by 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 I_{Ca, L} current.

R965

天津市教委科研计划项目（2017KJ224）