中国药物警戒 ›› 2014, Vol. 11 ›› Issue (8): 449-452.

• 基础与临床研究 •    下一篇

柴胡皂苷a对小鼠急性毒性实验研究

李晓宇1, 尹利顺1, 2, 孙蓉1*   

  1. 1山东省中医药研究院,山东 济南 250014;
    2山东中医药大学,山东 济南 250014
  • 收稿日期:2016-02-03 修回日期:2016-02-03 出版日期:2014-08-08 发布日期:2016-03-02
  • 通讯作者: 孙蓉,女,博士,研究员·博导,中药药理与毒理研究与评价。E-mail:sunrong107@163.com
  • 作者简介:李晓宇,女,硕士,中药药理与毒理。
  • 基金资助:
    基金项目:山东省自然科学基金重点课题(2011ZRB14333),山东省科技平台建设项目课题(2008GG2NS02021),国家自然科学基金课题(81073148,30672649)

Experimental Study on Mice's Acute Toxicity of Saikosaponin a

LI Xiao-yu1, YIN Li-shun1, 2, SUN Rong1, *   

  1. 1Shandong Academy of Chinese Medicine, Shandong Jinan 250014, China;
    2Shandong University of Traditional Chinese Medicine, Shandong Jinan 250355, China
  • Received:2016-02-03 Revised:2016-02-03 Online:2014-08-08 Published:2016-03-02

摘要: 目的探讨柴胡皂苷a对小鼠急性毒性的影响。方法采用经典的小鼠急性毒性实验方法,进行柴胡皂苷a不同给药方式对小鼠的急性毒性研究,实验数据用千克体重法计算灌胃给药的最大给药量(MLD)和腹腔给药半数致死量(LD50),连续观察14天。结果按柴胡皂苷a含量计算,柴胡皂苷a灌胃给药的MLD为790.5 mg·kg-1·d-1,腹腔给药小鼠的半数致死量(LD50)为72.511 mg·kg-1·d-1,95%的可信限为66.523 ~ 78.894 mg·kg-1·d-1。柴胡皂苷a 对小鼠腹腔注射给药,死亡小鼠急性毒性主要表现为安静怠动,即而出现后肢无力、走路不稳、俯卧不动、眼睑下垂、昏睡、呼吸急促、后肢连续性抽搐、神经抑制而死亡。存活小鼠在14 d观察期内体重增长相对缓慢,与空白对照组比较有明显差异。死亡小鼠解剖观察,有肝脏病变,余未见明显异常。结论腹腔注射柴胡皂苷 a 的小鼠急性毒性大,毒性反应更加强烈,进一步证实了柴胡皂苷a 是柴胡总皂苷和柴胡产生毒性的主要化学成分之一。其在体内蓄积毒性的“量-时-毒”关系以及在体内、外的生物转化过程,毒性作用部位、机制,还有待于进一步深入研究。

关键词: 柴胡皂苷a, 小鼠, 急性毒性, 最大给药量, 半数致死量

Abstract: ObjectiveTo discuss the effect of Saikosaponin a on mice's acute toxicity. MethodsMice's acute toxicities of different drug-delivery ways were tested respectively by the classic methods of acute toxicity. The MLD of ig and the LD50 of ip were calculated by a kilogram of body weight method, and continuously observing for 14 days.ResultsCaculated by Saikosaponin a, the MLD of ig is 790.5 mg·kg-1·d-1, the LD50 of ip is 72.511 mg·kg-1·d-1,and the 95% confidence interval is 66.523~78.894 mg·kg-1·d-1. The main acute toxicity symptoms and signs of dead mice are negligent action, then arising from rear limb weakness, unsteady gait, abdominal lying sleeping, drooping eyelids, lethargy, shortness of breath, continuous convulsions of hind legs, neurological inhibition, and eventually to death by ip. The surviving mice's weight gainings are more slower in 14 d obervation period and by anatomical observation of death mice, there are no other obvious abnormalities except hepatic pathological changes. ConclusionThe acute toxicity of intraperitoneal injection of Saikosaponin a is bigger than ig and we further confirm that Saikosaponin a is one of mainly toxical material compositions of Bupleurum. The "dose-time-poison"relationships of accumulated toxicity, biotransformation process in vivo and vitro, and the position and mechanism of toxic effects are to be further studied.

Key words: saikosaponin a, mice, acute toxicity, MLD, LD50

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