中国药物警戒 ›› 2012, Vol. 9 ›› Issue (12): 713-717.

• 专栏 • 上一篇    下一篇

北豆根不同组分单次给药对小鼠肝毒性“量-时-毒”关系研究

谢元璋1, 2, 孙蓉1*, 王懿3, 张亚囡3, 罗栋3   

  1. 1 山东省中医药研究院,山东 济南 250014；
    2 哈尔滨商业大学 生命科学与环境科学研究中心,黑龙江 哈尔滨150076；
    3 山东中医药大学,山东 济南 250355
  • 收稿日期:2012-10-22 出版日期:2012-12-10 发布日期:2015-08-07
  • 通讯作者: 孙蓉,女,博士,研究员,博士生导师,中药药理与毒理。E-mail： sunrong107@163.com
  • 作者简介:谢元璋,男,在读硕士研究生,药理学。。
  • 基金资助:
    有毒中药的毒性与功效、证候关系的基础研究,课题编号：2009CB522802

Experimental Study on the "Dose-time-toxicity" Relationship of Acute Hepatotoxicity Induced by Different Components from Rhizoma Menispermi in Mice

XIE Yuan-zhang1, 2, SUN Rong1*, WANG Yi3, ZHANG Ya-nan3, LUO Dong3   

  1. 1 Shandong Research Academy of TCM, Shandong Jinan 250014, China;
    2 Center of Research and Development on Life Sciences and Environmental Sciences, Harbin University of Commerce, Heilongjiang Harbin 150076, China;
    3 Shandong University of Traditional Chinese Medicine, Shandong Jinan 250355, China
  • Received:2012-10-22 Online:2012-12-10 Published:2015-08-07

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摘要： 目的观察北豆根不同组分单次给药对小鼠肝毒性“量-时-毒”关系的影响。方法取小鼠按不同时间点或不同剂量分组,观察给药后小鼠死亡情况和毒性反应,分别于药后不同时间检测血清谷丙转氨酶（ALT）、谷草转氨酶（AST）,计算肝脏指数,光镜下观察肝组织的病理变化。结果小鼠灌胃较高剂量的北豆根水提组分和醇提组分后,血清ALT、AST活力在4 h达到高峰,持续时间均约达48 h;水提组分给药6 h后即可出现肝脏明显肿大,肝脏指数升高,其中24 h肝脏指数升高最为明显;光镜下观察北豆根水提组分6h后,肝小叶结构尚还正常,个别细胞变性坏死;12h后大部分细胞核固缩,出现广泛的气球样变、玻璃样变、嗜酸性变性等,有假小叶形成;72h后肝细胞形态基本恢复正常,仍有个别细胞核固缩;醇提组分给药4 h后肝脏明显肿大,肝脏指数升高,其中24 h肝脏指数升高最为明显,光镜下观察北豆根醇组分6 h后,肝小叶结构尚还正常,部分肝细胞核固缩;12 h后,大部分细胞核固缩,间质细胞变性坏死;72h后部分肝细胞变性坏死。结论北豆根水提组分剂量在46.05~61.4g ·kg-1之间、醇提组分在8.45~15.02g ·kg-1之间对肝组织产生明显损伤,光镜下观察出现不同程度的肝细胞损伤;且随着剂量增大,ALT、AST升高显著,病理损伤更严重。小鼠单次灌胃给予一定剂量的北豆根水提组分或醇提组分可造成急性肝损伤,并呈现一定的“量-时-毒”关系。关于其肝脏损伤的机制有待进一步研究。

关键词: 北豆根, 不同组分, 小鼠, 肝毒性, “, 量-时-毒”, 关系

Abstract: Objective To study the "dose-time-toxicity" relationship of hepatotoxicity caused by single dose water extracted and alcohol extracted components from Rhizoma Menispermi in mice. Methods Mice are grouped according to different time or dose points, the death condition and toxicity of mice were observed, the activity of ALT、AST in serum were detected, liver index was calculated. Results Compared with the control group, ALT, AST level in serum of water extracted and alcohol extracted components are peaked after 4 hours' administration, and restored near normality after 48 hours; the water extracted components of(46.05~61.4)g ·kg-1 and alcohol extracted components of(8.45~15.02)g ·kg-1 have obvious damage to the liver organization, and ALT, AST in serum increased significantly with the dose increasing. Conclusion The water extracted and alcohol extracted components gavages certain dose one time to mice could cause obvious acute hepatic injury, and there were certain time-toxicity and dose-toxicity relationships.

Key words: Rhizoma Menispermi, water and alcohol extracted components, mice, hepatotoxicity, "dose-time-toxicity" relationship