| 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 |
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| 引用本文： | 崔利利,孔淑君,程欣,金文彬,徐颖,张景莲,王丽,马云淑. 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[J]. 中药新药与临床药理, 2024, 35(4): 500-505 |
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| 作者姓名： | 崔利利 孔淑君 程欣 金文彬 徐颖 张景莲 王丽 马云淑 |
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| 作者单位： | （1.云南中医药大学中药学院，云南 昆明 650500；2.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；3.迪沙药业集团有限公司，山东 威海 264200；4.云南省傣医药与彝医药重点实验室，云南 昆明 650500；5.云南省药食同源饮品工程研究中心，云南 昆明 650500） |
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| 基金项目： | 国家自然科学基金项目（82060723）。 |
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| 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...
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| 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 |
Study on the Acute Toxicity and Antiarrhythmic Effects of Two Kinds of Long-Circulating CrebanineNanoparticles |
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| CUI Lili,KONG Shujun,CHENG Xin,JIN Wenbin,XU Ying,ZHANG Jinglian,WANG Li,MAYunshu. Study on the Acute Toxicity and Antiarrhythmic Effects of Two Kinds of Long-Circulating CrebanineNanoparticles[J]. Traditional Chinese Drug Research & Clinical Pharmacology, 2024, 35(4): 500-505 |
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| Authors: | CUI Lili KONG Shujun CHENG Xin JIN Wenbin XU Ying ZHANG Jinglian WANG Li MAYunshu |
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| Affiliation: | （1. College of Chinese Material Medica，Yunnan University of Traditional Chinese Medicine，Kunming650500 Yunnan，China；2. Yunnan Key Laboratory of External Drug Delivery System and Preparation Technology inUniversities， Kunming 650500 Yunnan， China； 3. Disha Pharmaceutical Group Co. Led.， Weihai 264200Shandong， China； 4. Yunnan Key Laboratory of Dai and Yi Medicine ， Kunming 650500 Yunnan， China ；5. Engineering Research Center for Medicine and Homologous Beverage of Yunnan Province，Yunnan University ofTraditional Chinese Medicine，Kunming 650500 Yunnan，China） |
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| Abstract: | To compare the acute toxicity and antiarrhythmic effect of the two kinds of long-circulatingCrebanine （Cre） nanoparticles （PELGE-Cre-NPs， PLGA-Cre-NPs） prepared from two PEG-modified carriermaterials（PELGE，PLGA），and to explore their synergistic and attenuated effects. Methods The acute toxicity testof PLGA-Cre-NPs and PELGE-Cre-NPs in mice were conducted by using Bliss method， and LD50 values werecalculated by using of statistical software. The effect of PLGA-Cre-NPs and PELGE-Cre-NPs on ventricularfibrillation 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 afterintravenous injection were 13.619 mg·kg-1 and 14.839 mg·kg-1，respectively，which showed an obvious increase inLD50 compared to that of Cre （LD50，9.382 mg·kg-1）. Compared with the model control group，both nanoparticlessignificantly inhibited chloroform-induced ventricular fibrillation in mice and barium chloride- induced arrhythmia inrats， 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 ofaconitine in cardiac arrest was significantly increased （P＜0.05）. Conclusion The toxicity of PLGA-Cre-NPs andPELGE-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. |
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| Keywords: | Crebanine； long-circulating nanoparticles； PELGE-Cre-NPs； PLGA-Cre-NPs； acute toxicity；antiarrhythmic effect；rats；mice |
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