对两种经PEG 修饰载体材料（PELGE、PLGA）制备的克班宁（Crebanine，Cre）长循环纳米粒 （PELGE-Cre-NPs、PLGA-Cre-NPs）进行急性毒性试验与抗心律失常作用研究，探讨其增效减毒的效果。 方法 采用Bliss 法对PELGE-Cre-NPs 与PLGA-Cre-NPs 进行小鼠急性毒性试验，求半数致死量（LD50）；采用 氯仿诱发小鼠心室纤颤模型、氯化钡（BaCl2）及乌头碱致心律失常大鼠模型对两种纳米粒进行药效作用考察。 结果 PLGA-Cre-NPs 与PELGE-Cre-NPs 静脉注射的LD50 分别为13.619 mg·kg-1 与14.839 mg·kg-1，均比克班 宁静脉注射的LD50 （9.382 mg·kg-1）明显增加。与模型对照组比较，两种纳米粒均能明显对抗氯仿诱发的小鼠心 室纤颤、对抗氯化钡诱导的大鼠心律失常，明显提高乌头碱诱发大鼠室性早搏（VPB）、室性心动过速（VT）、 心室纤颤（VF）及心脏停搏（CA）的阈剂量（P＜0.05，P＜0.01，P＜0.001）。与克班宁 （5 mg·kg-1）实验组比较， PELGE-Cre-NPs 高剂量（5 mg·kg-1）组恢复窦性心律维持时间≥5 min 的鼠数量明显增多（P＜0.05），心脏停搏乌 头碱阈剂量明显提高（P＜0.05）。结论 两种材料纳米粒PLGA-Cre-NPs 与PELGE-Cre-NPs 的毒性较克班宁 小，并具有较明显的抗心律失常活性，且作用效果强于游离克班宁，达到增效减毒作用。

To compare the acute toxicity and antiarrhythmic effect of the two kinds of long-circulating Crebanine （Cre） nanoparticles （PELGE-Cre-NPs， PLGA-Cre-NPs） prepared from two PEG-modified carrier materials（PELGE，PLGA），and to explore their synergistic and attenuated effects. Methods The acute toxicity test of PLGA-Cre-NPs and PELGE-Cre-NPs in mice were conducted by using Bliss method， and LD50 values were calculated by using of statistical software. The effect of PLGA-Cre-NPs and PELGE-Cre-NPs on ventricular fibrillation caused by trichloromethane in mice， ventricular arrhythmia caused by BaCl2 in rats and arrhythmia caused by aconitine in rats was observed. Results The LD50 of PLGA-Cre-NPs and PELGE-Cre-NPs after intravenous injection were 13.619 mg·kg-1 and 14.839 mg·kg-1，respectively，which showed an obvious increase in LD50 compared to that of Cre （LD50，9.382 mg·kg-1）. Compared with the model control group，both nanoparticles significantly inhibited chloroform-induced ventricular fibrillation in mice and barium chloride- induced arrhythmia in rats， and significantly increased the threshold dose of aconitine induced ventricular premature beat （VPB）， ventricular tachycardia （VT），ventricular fibrillation （VF） and cardiac arrest （CA） in rats （P＜0.05，P＜0.01， P＜0.001）. Compared with Cre （5 mg·kg-1） group， the number of mice with high-dose of PELGE-Cre-NPs （5 mg·kg-1） restored sinus rhythm for ≥ 5 minutes was significantly increased （P＜0.05）. The threshold dose of aconitine in cardiac arrest was significantly increased （P＜0.05）. Conclusion The toxicity of PLGA-Cre-NPs and PELGE-Cre-NPs were lower than that of Cre， and they had significant antiarrhythmic activity. Moreover， nanoparticles displayed stronger effect than Cre，and they can reduce toxicity of Cre.

R285.5

国家自然科学基金项目（82060723）。