【摘要】 目的:制备LQT₃模型（一种QT延长综合症）,研究美西律对LQT₃模型的作用。方法:用ATX Ⅱ制备LQT₃模型,在钠通道、动作电位和心电图三个水平观察美西律对豚鼠LQT₃模型的作用。结果:用ATX Ⅱ作用后,心肌细胞的钠通道长期开放模式的发生频率和开放时间常数显著性增加:动作电位APD₅₀和APD₉₀分别延长25.8％、26.1％;0期最大除极速度增加12％:QT间期和QTc分别增加12.8％和16.9％。在ATX Ⅱ存在的同时加入美西律（0.7 mmol/L）,钠通道的开放几率明显降低。ATX Ⅱ（40 nmol/L）使动作电位时程延长后,美西律（1,5,15,45,70 μmol/L）使APD₅₀分别缩短0.5％,6.7％,14.4％,19.4％,18.8％,同时也使APD₉₀,V_max呈相应的减小。在整体动物心电图记录中,美西律呈剂量依赖性缩短由ATX Ⅱ引起的QT和QTc延长效应。结论:美西律可以用来治疗LQT₃。更多还原

【Abstract】 AIM: To make a LQT₃ model （one form of the long QT syndromes） and to investigate the effect of mexiletine on LQT₃. METHODS: Sea anemone toxin （ATX Ⅱ） was used to produce the LQT₃ model. The Effect of mexiletine on LQT₃ was performed on single Na channel, action potential, and electrocardiography in guinea pigs. RESULTS: With the binding of ATX Ⅱ to the Na⁺ channels, the probability of being in the open state and the open time constant of single Na⁺ channel with long opening mode increased significantly. Action potential duration APD₅₀, APD₉₀, and the maximal upstroke velocity of phase 0 were increased by 25.8%, 26.1%, and 12%, respectively. The QT interval and QTc, a rectified QT interval, increased by 12.8 % and 16.9%. On the contrary, after application of mexiletine, the open probability of single Na⁺ channel was reduced greatly. In the presence of ATX Ⅱ （40 nmol/L）, mexiletine （1, 5, 15, 45, 70 μmol/L） shortened the APD₅₀ by 0.5%, 6.7%, 14.4%, 19.4%, and 18.8%, respectively, and decreased the APD₉₀ and V_max accordingly. In the experiments with ECG, mexiletine reversed the ATX Ⅱ-produced prolongation effects on QTc in a dose-dependent manner. CONCLUSION: Mexiletine may be an effective drug in the treatment of LQT₃.更多还原