活心丸对小鼠的急性毒性研究

doi:10.19803/j.1672-8629.2021.10.06

中国药物警戒 ›› 2021, Vol. 18 ›› Issue (10): 924-929.
DOI: 10.19803/j.1672-8629.2021.10.06

活心丸对小鼠的急性毒性研究

莫尊汇¹, 陈美先¹, 王鹏程¹, 王羚郦^1,2, 廖弈秋³, 李泽华^4,*

¹广州中医药大学中医药数理工程研究院,广东广州 510006;
²东莞广州中医药大学中医药数理工程研究院,广东东莞 523808;
³广州白云山医药集团股份有限公司白云山制药总厂药研所/广东省化学药原料与制剂关键技术研究企业重点实验室,广东广州 510515;
⁴长沙市中心医院,湖南长沙 410004

收稿日期:2020-09-24 出版日期:2021-10-15 发布日期:2021-10-27
通讯作者: ^*李泽华,男,硕士,副主任医师,心脏介入治疗。E-mail：30488393@qq.com
作者简介:莫尊汇,男,硕士,中药新药筛选与开发。
基金资助:
国家重点研发计划（2017YFC1703701）; 广州市科技计划项目（2021103000049）

Acute Toxicity of Huoxin Pills in Mice

MO Zunhui¹, CHEN Meixian¹, WANG Pengcheng¹, WANG Lingli^1,2, LIAO Yiqiu³, LI Zehua^4*

¹Mathematical Engineering Academy of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou Guangdong 510006, China;
²Dongguang Mathematical Engineering Academy of Chinese Medicine, Guangzhou University of Chinese Medicine, Dongguan Guangdong 523808, China;
³Institute of Pharmacy, Baiyunshan Pharmaceutical General Factory, Guangzhou Baiyunshan Pharmaceutical Holdings Co. Ltd./Key Laboratory of Key Technology Research on Chemical Raw Materials and Prepartions of Guangzhou Province, Guangzhou Guangdong 510515, China;
⁴Changsha Central Hospital, Changsha Hunan 410004, China

Received:2020-09-24 Online:2021-10-15 Published:2021-10-27

摘要/Abstract

摘要： 目的观察活心丸对小鼠的急性毒性。方法因未能测得半数致死量（LD₅₀）,故采用最大耐受量（MTD）试验。取SPF级KM小鼠80只,雌雄各半,随机分为空白对照组和给药组,24 h内单次经口给药,给药组给予3.5 g/kg活心丸药液,对照组给予等体积生理盐水。给药后密切观察小鼠一般情况,连续观察14 d,于给药前和给药后1、3、5、8、14 d记录小鼠体质量、摄食量及饮水量。给药后1 d及14 d各组雌雄分别取10只,摘除眼球采血,检测血常规及血液生化指标,解剖观察各脏器,取心、肝、脾、肺、肾,称重并计算脏器指数,制作HE切片,进行病理学检查。结果给药后3 h内给药组小鼠出现中毒症状,表现为运动失调、精神萎靡、俯卧抽搐、呼吸急促,第2天给药组小鼠恢复正常。给药1 d后给药组雄鼠摄食量较对照组明显下降（P<0.05）,给药后3 d各组摄食量无明显变化。与对照组比较,给药组体质量、饮水量、脏器指数、血常规及血液生化指标均无显著性差异（P>0.05）。组织病理学显示给药组心脏心外膜及肝脏中央静脉出现炎性细胞浸润,且肝细胞轻度空泡化。结论小鼠口服给药活心丸的最大耐受量为3.5 g/kg,为60 kg成人每日用药剂量的1 750倍,证明口服活心丸毒性较小,安全性良好。

关键词: 活心丸, 急性毒性, 最大耐受量, 小鼠, 毒性靶器官

Abstract: Objective To investigate the acute toxicity of Huoxin pills in mice. Methods The maximum tolerance dose (MTD) test was chosen due to the unmeasurable LD₅₀. Eighty SPF-grade KM mice (half male and half female) were randomly divided into the blank control group and treatment group, and a single intragastric administration was given within 24 hours. The treatment group was given 3.5 g/kg Huoxin pill liquid, while the control group was given the same volume of normal saline. After administration, the mice were observed for 14 consecutive days. The body weight, food intake and water consumption of mice were recorded before administration and 1, 3, 5, 8, and 14 days after administration. Ten males and females were chosen from each group at 1 d and 14 d after administration, and blood was drawn after removal of the eyeballs. The blood routine analysis was conducted and blood biochemical indicators were detected. The changes of dissected organs were observed, and the heart, liver, spleen, lung, and kidney were also dissected for histopathological examination. Results Within 3 hours of administration the mice showed symptoms of poisoning, including ataxia, malaise, prone convulsions and accelerated breathing. The second day, mice in the treated group returned to normal. The food intake of male mice in the treatment group was significantly lower than that in the control group at the first day after administration (P<0.05), but there was no significant change in the food intake of either group 3 days after administration. Compared with the control group, no significant change in body weight, water consumption, organ indexes, blood routine analysis, or blood biochemical indexes was observed in the treatment group (P>0.05). Histopathology showed inflammatory cell infiltration in the heart epicardium, inflammatory cell infiltration in the central vein of livers, and slight vacuolation of hepatocytes in the treatment group. Conclusion The maximum tolerance dose of mice is orally 3.5 g/kg, which is 1 750 times the daily dosage of a 60 kg adult, suggesting that Huoxin pills are orally safe.

Key words: Huoxin pills, acute toxicity, maximum tolerance test, mice, toxical target organs

中图分类号:

R994.1

莫尊汇, 陈美先, 王鹏程, 王羚郦, 廖弈秋, 李泽华. 活心丸对小鼠的急性毒性研究[J]. 中国药物警戒, 2021, 18(10): 924-929.

MO Zunhui, CHEN Meixian, WANG Pengcheng, WANG Lingli, LIAO Yiqiu, LI Zehua. Acute Toxicity of Huoxin Pills in Mice[J]. Chinese Journal of Pharmacovigilance, 2021, 18(10): 924-929.

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活心丸对小鼠的急性毒性研究

Acute Toxicity of Huoxin Pills in Mice

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