两种克班宁长循环纳米粒的急性毒性与抗心律失常作用研究
Study on the Acute Toxicity and Antiarrhythmic Effects of Two Kinds of Long-Circulating Crebanine Nanoparticles
崔利利 1孔淑君 2程欣 1金文彬 3徐颖 3张景莲 3王丽 3马云淑4
作者信息
- 1. 云南中医药大学中药学院,云南 昆明 650500;云南省高校外用给药系统与制剂技术重点实验室,云南 昆明 650500
- 2. 云南中医药大学中药学院,云南 昆明 650500;迪沙药业集团有限公司,山东 威海 264200
- 3. 云南中医药大学中药学院,云南 昆明 650500
- 4. 云南中医药大学中药学院,云南 昆明 650500;云南省傣医药与彝医药重点实验室,云南 昆明 650500;云南省药食同源饮品工程研究中心,云南 昆明 650500
- 折叠
摘要
目的 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.
Abstract
Objective 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.
关键词
克班宁/长循环纳米粒/PELGE-Cre-NPs/PLGA-Cre-NPs/急性毒性/抗心律失常作用/大鼠/小鼠Key words
Crebanine/long-circulating nanoparticles/PELGE-Cre-NPs/PLGA-Cre-NPs/acute toxicity/antiarrhythmic effect/rats/mice引用本文复制引用
出版年
2024
NETL
NSTL
万方数据