蝙蝠葛碱对心肌电生理和肌浆网Ca^(2+)-ATP酶的效应及其与汉防己甲素比较研究

The effect of dauricine on the myocardial electrophysiology and the Ca^(2+) ATP ase of sarcoplasmic reticulum in comparison with the action of tetrandrine

目的 比较中药蝙蝠葛碱 (Dau)及汉防己甲素 (Tet)的细胞电生理效应及对心肌肌浆网Ca2 +-ATP酶的影响 ,为临床用药提供实验及理论依据。 方法 用玻璃微电极的方法 ,观察用药前后心肌细胞动作电位 (AP)、d V/ dt、峰张力 (PT)及 d T/ dt等指标的改变 ,并用生化方法观察上述两种药对心肌肌浆网钙吸收率及无机磷释放等指标的变化。 结果 蝙蝠葛碱延长了快动作电位 (FAP)的动作电位时限 (APD) ,包括 APD2 0 和 APD90 及慢动作电位 (SAP)的 APD90 ,且 APD90 增宽明显 (P<0 .0 5) ;却缩短了 SAP的 APD2 0 。汉防己甲素虽亦轻度延长了 FAP的 APD90 ,但差异无统计学意义。它主要缩短了 SAP的 APD2 0 、APD90 。两种药均抑制了动作电位幅度 (APA)、PT、d T/ dt和钙摄取率 ,磷的释放 ,对后四项的作用以汉防己甲素更为明显。 结论 蝙蝠葛碱轻度抑制了钙离子内流及 Ca2 +-ATP酶的活性 ,但具有明显抑制钠离子内流及钾离子外流的作用 ,尤其是阻滞延迟钾外流作用更为明显 ,其电生理的作用机制类似 类抗心律常药胺碘酮。

Objective This study is aimed at comparing the effect of two Chinese traditional drugs,Dauricine and Tetrandrine, on the myocardial electrophysiology and the sarcoplasmic reticulum Ca 2+ ATPase. Methods Changes of AP、dV/dt、PT and dT/dt of myocardial cells were studied by using the technique of glass electrode,and changes of the calcium uptake rate by sarcoplasmic reticulum and release of inorganic phosphate from sarcoplasmic reticulum were assessed with biochemical techniques after administration. Results Dauricine has the effect of prolonging the APD 20 ,APD 90 of FAP and the APD 90 of SAP,particularly widening APD 90 ( P <0.05), but the APD 20 of SAP is shortened.Although tetrandrine prolongs slightly the APD 90 of FAP(No statistic difference),it shortens obviously the APD 20 and APD 90 of SAP.Both drugs inhibit APA、PT、dT/dt and absorption rate of calcium and release of inorganic phosphate.The action of the latter four items are more evident with the use of tetrandrine. Conclusion Dauricine slightly inhibits the calcium influx and activity of Ca 2+ ATPase,but evidently inhibits the sodium influx and potassium efflux,especially delayed potassium efflux blocked.The electrophysiologic mechanism is similar to that of a class Ⅲ anti arrhythmic drug amiodarone.