中国药物警戒 ›› 2024, Vol. 21 ›› Issue (8): 878-883.
DOI: 10.19803/j.1672-8629.20230792

• 基础与临床研究 • 上一篇    下一篇

智脑胶囊长期毒性研究

王岩1, 滕晶晶1, 杨同金1, 夏新1, 喻丹丹1, 占海兵1, 杨文明2,*   

  1. 1安徽省疾病预防控制中心,安徽 合肥 230601;
    2安徽中医药大学第一附属医院,安徽 合肥 230031
  • 收稿日期:2023-12-02 出版日期:2024-08-15 发布日期:2024-08-21
  • 通讯作者: *杨文明,男,博士,主任医师·博导,脑血管病及锥体外系疾病。
  • 作者简介:王岩,男,硕士,副主任医师,毒理学。
  • 基金资助:
    安徽省科技重大专项项目（201903a07020016）; 安徽高校协同创新项目（GXXT-2020-025）

Chronic toxicity study of Zhinao capsules in SD rats

WANG Yan1, TENG Jingjing1, YANG Tongjin1, XIA Xin1, YU Dandan1, ZHAN Haibing1, YANG Wenming2,*   

  1. 1Anhui Provincial Center for Disease Control and Prevention, Hefei Anhui 230601, China;
    2The First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei Anhui 230031, China
  • Received:2023-12-02 Online:2024-08-15 Published:2024-08-21

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摘要： 目的 评价智脑胶囊长期毒性效应,为临床安全用药提供毒理学参考。方法 将160只大鼠随机分为4组,即阴性对照组（纯水）和智脑胶囊高、中、低3个剂量组（6 400、2 100、710 mg·kg-1）,每组40只大鼠,连续给药26周,观察各组大鼠一般状况、体重及摄食量。在给药13周、26周及恢复期2周,各组分别解剖10、20、10只大鼠,检测血液学、血液生化学、脏器系数和病理组织学变化。结果 与阴性对照组比较,雄鼠高剂量组体重从第13周到第21周出现显著降低(P<0.05),在26周恢复正常（P>0.05）;中、高剂量组大鼠血液学和血液生化少部分指标出现显著升高和降低（P<0.05）,但均在正常生理波动范围内;给药26周高剂量组雄鼠肾脏/体积比、雌鼠肝/体积比及卵巢/体积比出现显著升高（P<0.05）,恢复期2周各剂量组脏体积比均无显著性差异（P>0.05）;各剂量组均未见与药物明显有关的不可逆组织病理改变。结论 智脑胶囊长期给药具有较高的安全性,其最大未观察到有害作用剂量（NOAEL）值雌雄均为6 400 mg·kg-1,相当于临床日最大推荐用量95倍。

关键词: 智脑胶囊, 长期毒性, 安全性, SD大鼠, 剂量

Abstract: Objective To evaluate the chronic toxicity of Zhinao capsules to SD rats and to provide reference for safe clinical medications. Methods One hundred and sixty normal rats were randomly divided into four groups: the negative control group (pure water) and three-dosage groups of Zhinao capsules (6 400, 2 100 and 710 mg·kg-1), with 40 rats in each. The rats were orally administrated with Zhinao capsules for 26 weeks. The health status, food consumption and body weight of rats were observed during the test. At 13 weeks, 26 weeks and after two weeks of recovery, 10, 20 and 10 rats in each group were dissected respectively before hematology, blood biochemistry, the organ-body ratio and histopathology were measured. Results Compared with the negative control group, the body weight of male rats in the high-dose group decreased from week 13 to week 21 (P < 0.05) but returned to normal at 26 weeks (P > 0.05). Compared with the negative control group, some hematological and blood biochemical indexes of rats in the medium and high dose groups were increased before they decreased (P < 0.05), but all were within the normal range. Compared with the negative control group, the male kidney/body ratio, the female liver/body ratio and the ovary/body ratio were increased in the high dose group after 26 weeks of administration (P < 0.05). There was no difference in the organ-body ratio between the three groups in the two weeks of recovery (P > 0.05), and no histopathological lesions of organs induced by drugs were observed either. Conclusion Long-term administration of Zhinao capsules is highly safety, and the NOAEL of Zhinao capsules is considered to be 6 400 mg·kg-1, equal to 95 times the proposed clinical adult .

Key words: Zhinao capsules, chronic toxicity, safety, SD rats, dosages

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