中国药物警戒 ›› 2018, Vol. 15 ›› Issue (10): 587-594.

• 基础与临床研究 • 上一篇    下一篇

黄曲霉毒素B1对Fischer344雄性大鼠的急性肝毒性研究

张凡, 李梅, 孙华*   

  1. 中国医学科学院 北京协和医学院药物研究所,天然药物活性物质与功能国家重点实验室,北京 100050
  • 收稿日期:2018-09-18 修回日期:2018-11-27 出版日期:2018-10-20 发布日期:2018-11-27
  • 通讯作者: 孙华,女,博士,副研究员·硕导,肝脏病药理学。E-mail:sunhua@imm.ac.cn
  • 作者简介:张凡,女,在读硕士,肝脏病药理学。
  • 基金资助:
    中国医学科学院医学与健康科技创新工程重大协同创新项目(2017-12M-1-013):中药安全风险预警及防控

Acute Hepatotoxicity of Aflatoxin B1 in Male Fischer 344 Rats

ZHANG Fan, LI Mei, SUN Hua*   

  1. Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China
  • Received:2018-09-18 Revised:2018-11-27 Online:2018-10-20 Published:2018-11-27

摘要: 目的 考察不同浓度的黄曲霉毒素B1(Aflatoxin B1,AFB1)给药不同次数对Fischer 344雄性大鼠的急性肝毒性作用。方法 Fischer 344雄性大鼠连续灌胃给予AFB1 0.5、1.0、2.0 mg·kg-1,每天1次,共给药3天。记录动物死亡情况,并于每次给药后24 h眼静脉丛取血,制备血清。继续观察动物状态1周后,动物禁食不禁水16 h,取血制备血清,取肝脏、脾脏及肾脏称重并计算脏器指数。全自动生化分析仪检测血清中ALT、AST、LDH、ALP、GGT、T.Bili、D.Bili含量,并取肝组织做病理检查。结果 AFB1 0.5、1.0、2.0 mg·kg-1灌胃给予Fischer 344大鼠,大鼠血清肝功能生化指标呈现剂量和时间依赖性显著升高;连续给药3次,存活大鼠生化指标出现“胆酶分离”的严重肝损伤状态;停药1周,肝功能未有显著改善。实验中动物体重剂量依赖性降低,连续给药2次,高剂量大鼠即出现死亡,后中高剂量组大鼠陆续死亡。同时,停药1周后,AFB1中高剂量组存活大鼠肝指数降低,高剂量组大鼠肾脏水肿,脾脏萎缩。HE染色结果显示,AFB1各组动物肝脏均出现炎症及坏死病变。结论 AFB1 0.5、1.0、2.0 mg·kg-1灌胃给药,能引起雄性Fischer 344大鼠显著的肝脏毒性,毒性作用呈现明显的剂量依赖性和时间依赖性关系,且高剂量累毒其他器官。该研究结果将为AFB1的毒性研究特别是急性毒性研究提供参考。

关键词: 黄曲霉毒素B1, Fischer 344大鼠, 急性肝毒性

Abstract: Objective To investigate the acute hepatotoxicity of aflatoxin B1 with different dosage and different times of administration in male Fischer 344 rats. Methods Fischer 344 rats were given AFB1 0.5, 1.0, 2.0 mg·kg-1 once daily for 3 days. 24 hours after each oral administration, blood was collected from venous plexus of eyes and serum was prepared. After final administration, animals were observed for one week and then all of the animals were fasted 16 h and treated to collect livers and blood, record body weights and wet weights of liver, spleen and kidney for calculating the organ indexes. The levels of serum ALT, AST, LDH, ALP, GGT, T.Bili, D.Bili were measured by automatic biochemical analyzer, and liver lobes were taken for pathological examination. Results Fischer 344 rats were given AFB1 0.5 ,1.0, 2.0 mg·kg-1 for 3 days, then the serum biochemical indicators were increased dosage and time dependently. Survival rats presented the phenomenon of separation of bile and transaminase, which indicated serious liver damage. The function of liver was not obviously improved after ceasing administration. During the experiment, the body weights of rats were decreased dosage dependently. After twice administration, there was death in high dosage. Finally, the liver indexes of survival rats in medium and high dosage group were decreased, and these rats in high dosage group were with renal edema and spleen atrophy. The Results of HE staining showed that there were inflammation and necrotic lesions in the liver of each group of AFB1 animals. Conclusion After oral administration of AFB1 0.5, 1.0, 2.0 mg·kg-1, Fischer 344 rats could display significant hepatotoxicity, which was obviously dosage and time dependent. And high dosage of AFB1 also presented toxicity in other organs. The research Results could provide reference for the study of toxicity of AFB1, especially acute toxicity.

Key words: aflatoxin B1, Fischer 344 rat, acute hepatotoxicity

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