目的 探究槐果堿對(duì)快速性室性心律失常的影響及其電生理調(diào)控機(jī)制。方法 應(yīng)用Langendorff離體心臟灌流的方法，結(jié)合電學(xué)和光學(xué)標(biāo)測系統(tǒng)，檢測槐果堿給藥前（對(duì)照）和給藥后豚鼠離體心電圖和電生理活動(dòng)的變化。采用單細(xì)胞膜片鉗技術(shù)評(píng)估槐果堿對(duì)豚鼠、大鼠單個(gè)心室肌細(xì)胞以及hERG-HEK293細(xì)胞離子通道的影響。將哇巴因誘導(dǎo)的快速性心律失常豚鼠分為模型組、普萘洛爾（25 mg/kg）組及槐果堿不同劑量（12.5、25.0、50.0 mg/kg）組，通過計(jì)算室性早搏、室顫和心臟停搏發(fā)生時(shí)的哇巴因用量來評(píng)估槐果堿在體內(nèi)的抗心律失常作用。結(jié)果 與對(duì)照組比較，槐果堿能夠降低心率，顯著延長豚鼠單個(gè)心室肌細(xì)胞動(dòng)作電位復(fù)極化90%時(shí)的時(shí)程（action potential duration at 90% repolarization，APD90，P＜0.01），100 μmol/L槐果堿能夠顯著抑制豚鼠心室肌細(xì)胞L-型鈣電流（L-type calcium current，I_Ca-L，P＜0.01）和大鼠心室肌細(xì)胞瞬時(shí)外向鉀電流（transient outward potassium current，Ito，P＜0.05）?；惫麎A對(duì)hERG-HEK293細(xì)胞電流具有劑量相關(guān)性的抑制作用。與模型組比較，槐果堿給藥組（50 mg/kg）可以顯著增加室性早搏和室顫（P＜0.05）發(fā)生時(shí)的哇巴因用量，證明其具有潛在的抗心律失?；钚?。結(jié)論 槐果堿具有多離子通道阻滯作用，在體外和體內(nèi)均顯示出抗心律失?；钚?。

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

河北省省級(jí)科技計(jì)劃資助項(xiàng)目（23379902L）;河北省省級(jí)科技計(jì)劃資助項(xiàng)目（24462501D）;石家莊市高層次科技創(chuàng)新創(chuàng)業(yè)人才項(xiàng)目（07202203）