苦参碱对哇巴因诱导钠电流改变的调节作用  

Modulation of Matrine on Sodium Current Induced by Ouabain

作　　者：周宇宏[1] 周佳莹[1] 王丽娟[1] 李俊男[1] 

机构地区：[1]哈尔滨医科大学药理教研室省部共建生物医药重点实验室,黑龙江哈尔滨150081

出　　处：《现代生物医学进展》2015年第29期5609-5612,5640,共5页Progress in Modern Biomedicine

基　　金：黑龙江省教育厅科研基金项目(12521175)

摘　　要：目的:探讨苦参碱拮抗哇巴因诱导的心律失常的作用机制。方法:应用全细胞膜片钳技术记录哇巴因对单个豚鼠心室肌细胞的Na+电流和动作电位时程作用后,观察苦参碱对哇巴因诱导Na+电流和动作电位时程改变的恢复作用。结果:1 5μmol·L-1哇巴因延长APD50从给药前476±40.7 ms增加到744±62.9 ms(n=6,P<0.05),APD90从给药前499±84.9 ms增加到775±87.7 ms(n=6,P<0.01),100μmol·L-1苦参碱恢复APD50至603±79.0 ms(n=6,P<0.05),APD90至630±81.6 ms(n=6,P<0.05);2 5μmol·L-1哇巴因可增加钠电流的峰值,在-20 m V电压条件下,5μmol·L-1哇巴因增加INa,由正常-40.9±2.32 p A/p F增加到-55.2±2.26 p A/p F(n=8,P<0.05),100μmol·L-1苦参碱减少INa至-34.6±2.14 p A/p F(n=8,P<0.05);5μmol·L-1哇巴因右移钠通道的激活曲线,并左移钠通道的失活曲线从而改变通道动力学特性;100μmol·L-1苦参碱可抑制哇巴因诱导的INa的增加,并恢复Na+通道动力学特性接近正常。结论:苦参碱拮抗哇巴因诱导的心律失常机制与其抑制哇巴因诱发细胞水平Na+电流的增加,缩短哇巴因诱发APD的延长有关。Objective： To investigate the antiarrhythmic effects of matrine. Methods： Ouabain was used to construct an arrhythmic model of cardiomyocytes, and the sodium current and action potential duration was recorded. Results： In cardiomyocytes of guinea pigs, ouabain of 5 μmol·L^-1 prolonged APD50 from 476 ＋ 40.7 ms to 744 ± 62.9 ms （n=6, P〈0.05） and APDg0 from 499 ＋ 84.9 ms to 775 ± 87.7 ms（n=6, P〈0.01）, 100 μmol·L^-1 matrine recovered APD50 to 603± 79.0 ms （n=6, P〈0.05）, APD90 to 630 t 81.6 ms （n=6, P〈0.05） respectively. Ouabain of 1 μmol·L^-1 increased peak sodium currents by shifting the activation and inactivation curve. Ouabain of 5 μmol·L^-1 increased the peak of sodium current. At -20 mV, ouabain of 5 μmol·L^-1 increased INa, from -40.9 ± 2.32 pA/pF to -55.2 ± 2.26 pA/pF （n=8, P〈0.05）, 100 μmol·L^-1 malafne decreased INa to -34.6 ± 2.14 pA/pF（n=8, P〈0.05）; matrine of 100 μmol·L^-1 recovered the activation and inactivation curve to close to the normal level. Conclusion： Taken together, these findings provided the first evidence that matrine could inhibit INa and shorten APD prolongation which contributed to its anti-arrhythmic effect.

关 键 词：苦参碱 哇巴因 钠离子通道 动作电位时程 

分 类 号：Q95-3[生物学—动物学] R285.5[医药卫生—中药学]