中国药物警戒 ›› 2011, Vol. 8 ›› Issue (1): 11-14.

• 半夏毒性物质基础研究 • 上一篇    下一篇

半夏水提组分对小鼠肝毒性“量-时-毒”关系研究

张丽美1, 鲍志烨2, 黄幼异2, 黄伟2, 张亚囡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 250355
  • 收稿日期:2010-10-08 出版日期:2011-01-10 发布日期:2015-08-24
  • 通讯作者: 孙蓉,女,研究员,硕士生导师,中药药理与毒理。E-mail：sunrong107@163.com
  • 作者简介:张丽美,女,硕士,中药药理与毒理。
  • 基金资助:
    国家重点基础研究发展计划 （973）中医基础理论专项资助项目 （2009CB522802）; 山东省科技平台建设项目（2008GG2NS0 2021）; 山东省中医局科技发展计划课题（2007-119）

Experimental Study on the "Dosage-Time-Toxicity" Relationship of Acute Hepatotoxicity Induced by Water Extraction from Rhizoma Pinelliae in Mice

ZHANG Li-mei1, BAO Zhi-ye2, HUANG You-yi2, HUANG wei2, ZHANG Ya-nan2, SUN Rong1   

  1. 1. Shandong Research Academy of TCM, Shandong Jinan 250014, China;
    2. Shandong University of Traditional Chinese Medicine, Shandong Jinan 250355, China
  • Received:2010-10-08 Online:2011-01-10 Published:2015-08-24

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摘要： 目的 考察半夏水提组分单次给药小鼠肝毒性“量-时-毒”关系。方法 单次给药“时-毒”关系研究：制备62.5 g·kg-1半夏水提组分,按25 mL·kg-1给小鼠灌胃给药1次,给药后按处理时间点依次为0（即空白对照组）,0.5,1,2,4,8,12,24,48,72h,于相应时间点取血,测定血清丙氨酸氨基转移酶（ALT）、天门冬氨酸氨基转移酶（AST）,取肝组织,常规染色,光学显微镜下观察其组织形态学变化;单次给药“量-毒”关系研究：设定半夏水提组分82.5 g·kg-1、70.1 g·kg-1、59.6 g·kg-1、50.7 g·kg-1、43.1 g·kg-1、36.6 g·kg-1 6个剂量组,小鼠灌胃给药1次,空白组给蒸馏水,于给药后4h按上述方法测定血清ALT、AST及肝组织镜检。结果 半夏肝毒性“时-毒”关系的研究显示小鼠单次灌胃62.5 g·kg-1的半夏水提组分血清ALT、AST值随时间的不同造成的肝损害的程度也不同,毒性高峰出现在给药后4h,持续约48h。肝组织病理形态学检查显示,半夏水提组分在给药后4h对肝组织产生明显损伤。半夏肝毒性“量-毒”关系的研究显示小鼠单次灌胃较高剂量半夏水提组分可使血清ALT、AST值显著升高。肝组织病理形态学检查显示给予较高剂量的半夏水提组分后,肝细胞可出现不同程度的水肿、脂肪变性以及部分点状坏死,而低剂量给小鼠灌胃,肝组织病理形态学未见异常改变。结论 单次给予半夏水提组分可造成小鼠肝毒性损伤,并呈现一定的“量-时-毒”关系。

关键词: 半夏, 小鼠, 肝毒, 量-时-毒

Abstract: ObjectiveTo study the "dosage-time-toxicity" relationship of hepatotoxicity induced by single intragastric administration of water extraction from Rhizoma Pinelliae. Methods"time-toxicity" relationship study:preparing water extraction of 62.5 g·kg-1, ig it of 25 mL·kg-1 to mice once,then get their blood sampling after administration at different times(0, 0.5, 1, 2, 4, 8, 12, 24, 48, 72h). The changes of the activity of ALT, AST and hepar index were detected and the histopathological study was performed; kg-1、70.1 g·kg-1、59.6 g·kg-1、50.7 g·kg-1、43.1 g·kg-1、36.6 g·kg-1, ig them to mice once,while ig distilled water to control group, then do the detecting work 4 hours later as above. Results"time-toxicity"relationship study indicates that the activity of serum ALT, AST is changing with the time, its toxic peak appears at 4th hour after administration and last for about 48 hours; "dosage-toxicity" relationship study indicates that the active of serum ALT, AST of high dosage groups were significantly increased than that of normal group.Hepatic tissue pathomorphology examination also shows that hydroncus, fatty degeneration and necrosis in hepatocyte could be induced after administration the high dosage samples,while the low dosage groups have no differences. ConclusionSingle intragastric administration of water extraction from Rhizoma Pinelliae with certain dosage may induce acute hepatotoxical injury in mice and show an obvious "dosage-time-toxicity" relationship.

Key words: Rhizoma Pinelliae, mice, hepatotoxicity, "dosage-time-toxicity", relationship

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