目的 探究槐果碱对快速性室性心律失常的影响及其电生理调控机制。方法 应用Langendorff离体心脏灌流的方法，结合电学和光学标测系统，检测槐果碱给药前（对照）和给药后豚鼠离体心电图和电生理活动的变化。采用单细胞膜片钳技术评估槐果碱对豚鼠、大鼠单个心室肌细胞以及hERG-HEK293细胞离子通道的影响。将哇巴因诱导的快速性心律失常豚鼠分为模型组、普萘洛尔（25 mg/kg）组及槐果碱不同剂量（12.5、25.0、50.0 mg/kg）组，通过计算室性早搏、室颤和心脏停搏发生时的哇巴因用量来评估槐果碱在体内的抗心律失常作用。结果 与对照组比较，槐果碱能够降低心率，显著延长豚鼠单个心室肌细胞动作电位复极化90%时的时程（action potential duration at 90% repolarization，APD90，P＜0.01），100 μmol/L槐果碱能够显著抑制豚鼠心室肌细胞L-型钙电流（L-type calcium current，I_Ca-L，P＜0.01）和大鼠心室肌细胞瞬时外向钾电流（transient outward potassium current，Ito，P＜0.05）。槐果碱对hERG-HEK293细胞电流具有剂量相关性的抑制作用。与模型组比较，槐果碱给药组（50 mg/kg）可以显著增加室性早搏和室颤（P＜0.05）发生时的哇巴因用量，证明其具有潜在的抗心律失常活性。结论 槐果碱具有多离子通道阻滞作用，在体外和体内均显示出抗心律失常活性。

Objective To comprehensively evaluate the effects of sophocarpine on ventricular tachyarrhythmias and its electrophysiological regulation mechanisms. Methods The Langendorff isolated heart perfusion method was used, combined with electrical and optical mapping systems, to detect changes in the isolated electrocardiogram and electrophysiological activity of guinea pigs before (control) and after sophocarpine administration. The effects of sophocarpine on ion channels in single ventricular myocytes from guinea pigs or rats and hERG-HEK293 cells were evaluated using the whole-cell patch-clamp technique. Guinea pigs with ouabain-induced tachyarrhythmia were divided into model group, propranolol (25 mg/kg) group, and different doses of sophocarpine (12.5, 25.0, 50.0 mg/kg) groups. The antiarrhythmic effect of sophocarpine in vivo was evaluated by calculating the dosage of ouabain during premature ventricular contractions, ventricular fibrillation and asystole. Results Sophocarpine reduced heart rate and significantly prolonged (P < 0.01) the action potential duration at 90% repolarization (APD90) in single guinea pig ventricular myocytes. At a concentration of 100 μmol/L, sophocarpine significantly inhibited the L-type calcium current (I_Ca-L, P < 0.01) in guinea pig ventricular myocytes and the transient outward potassium current (Ito, P < 0.05) in rat ventricular myocytes. Furthermore, sophocarpine exhibited a concentration-dependent inhibitory effect on hERG-HEK293 cell currents. Compared with model group, the sophocarpine administration group (50 mg/kg) required a significantly higher dose of ouabain to induce ventricular premature beats (P < 0.05) and ventricular fibrillation (P < 0.05), demonstrating its potential antiarrhythmic activity. Conclusion Sophocarpine has multiple ion channel blocking effects and exhibits antiarrhythmic activity both in vitro and in vivo.

R285.5

河北省省级科技计划资助项目（23379902L）;河北省省级科技计划资助项目（24462501D）;石家庄市高层次科技创新创业人才项目（07202203）