苦参碱对豚鼠心室肌细胞钠离子通道电流的影响

Influence of Matrine on Sodium Channel Current of Ventricle Muscle Cells in Guinea Pigs

摘要:

目的: 观察苦参碱对豚鼠心室肌细胞钠离子通道电流(I_Na)的影响,探讨其抗心律失常的作用机制。方法: 豚鼠随机分为正常对照组、乌头碱组和苦参碱组。每组8只。乌头碱组以50 μmol·L^-1乌头碱灌流10 min, 苦参碱组在乌头碱组基础上,以10,50,100 μmol·L^-1苦参碱灌流20 min。采用膜片钳全细胞记录技术记录豚鼠单个心肌细胞钠电流并绘制电流密度电流强度(PA)/细胞膜电容(pF)曲线。结果: 50 μmol·L^-1乌头碱显著增大I_Na(-92.62±6.5) pA/pF[和对照组比较(-66.24±4.8) pA/pF,P＜0.05]。在乌头碱灌流基础上,10 μmol·L^-1苦参碱对I_Na没有明显作用,50 μmol·L^-1可使I_Na减小至(-49.21±5.1) pA/pF(和乌头碱组比较P<0.05), 100 μmol·L^-1又使I_Na稍微增大(和对照组比较P>0.05)。结论: 苦参碱抑制I_Na电流,呈浓度依赖性,浓度较高时抑制I_Na电流作用减弱,表现为双向调节的药理作用,可能是苦参碱抗心律失常作用温和持久的机制之一。

Abstract:

Objective: To observe influence of matrine on sodium channel current(I_Na)of ventricle muscle cells in guinea pigs and to discuss its antiarrhythmic mechanism. Method: Guinea pigs were randomly divided into control group, aconitine group and matrine group. Each group included eight cases. Aconitine group was treated with 50 μmol·L^-1 aconitine perfusion 10 min while matrine group was treated with 10,50,100 μmol·L^-1 matrine based on aconitine group. The whole-cell patch clamp technique was used to record I_Nacurrent of single ventricle muscle cell and then to design figures of I_Na current density. Result: Aconitine(50 μmol·L^-1) could significantly amplify I_Na current(-92.62±6.5) pA/pF (compared with control group(-66.24±4.8,P<0.05). Based on aconitine-induced arrhythmia, matrine(10 μmol·L^-1) had no significant effects on I_Na current,however, matrine(50 μmol·L^-1) could significantly reduce I_Na current(-49.21±5.1) pA/pF (compared with aconitine group, P<0.05),but when the dose of matrine was kept increasing, the effect of reducing I_Na current of matrine were getting weak, and at the level of 100 μmol·L^-1, matrine could slightly amplify I_Na current (compared with control group, P>0.05). Conclusion: Matrine could restrict I_Na current in dose-dependent manner, and high dose of matrine could make this effect of restriction weak, so matrine has a two-way, modest and lasting regulation effect which probably was one of its antiarrhythmic mechanisms.