中国药物警戒 ›› 2020, Vol. 17 ›› Issue (10): 653-658.
DOI: 10.19803/j.1672-8629.2020.10.02

• 基础与临床研究 • 上一篇    下一篇

大鼠经口灌胃给予三七药酒26周重复给药毒性研究

夏丽娟1, 印晓红2,3,4, 张城达1, 杨倩1, 黄敏聪1, 谢方1, 陈云祥1, 陈蓬5, 郑高利1, 张立将1,*   

  1. 1杭州医学院（浙江省医学科学院）安全性评价研究中心,浙江 杭州 310053;
    2浙江康恩贝制药股份有限公司,浙江 杭州 310053;
    3浙江省中药制药技术重点实验室,浙江 杭州310053;
    4浙江工业大学,浙江 杭州 310014;
    5云南希陶绿色药业股份有限公司,云南 昆明 650217
  • 收稿日期:2020-10-14 修回日期:2020-10-14 出版日期:2020-10-15 发布日期:2020-10-13
  • 通讯作者: *张立将,男,博士,研究员,药物毒理学研究和评价。E-mail：zhanglj127@163.com
  • 作者简介:夏丽娟,女,硕士,助理研究员,药物毒理学。
  • 基金资助:
    国家重点研发计划项目（2018YFA0903200）; 浙江省基础公益研究计划项目（LGF18H310004）; 浙江省科研院所专项（数字化切片技术在毒性病理学中的应用）

Study on 6-month Repeated Dose Toxicity of Sanqi Yaojiu via Oral Administration in Rats

XIA Lijuan1, YIN Xiaohong2,3,4, ZHANG Chengda1, YANG Qian1, HUANG Mincong1, XIE Fang1, CHEN Yunxiang1, CHEN Peng5, ZHENG Gaoli1, ZHANG Lijiang1,*   

  1. 1Center of Safety Evaluation, Zhejiang Academy of Medical Sciences (Hangzhou Medical college),Hangzhou Zhejiang 310053, China;
    2Zhejiang Conba Pharmaceutical Co. Ltd., Hangzhou Zhejiang 310053, China;
    3Zhejiang Provincial Key Laboratory of Traditional Chinese Medicine Pharmaceutical Technology, Hangzhou Zhejiang 310053, China;
    4Zhejiang University of Technology, Hangzhou Zhejiang 310014, China;
    5Yunnan Xitao Green Pharmaceutical Co. Ltd., Kunming Yunnan 650217, China
  • Received:2020-10-14 Revised:2020-10-14 Online:2020-10-15 Published:2020-10-13

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摘要： 目的 观察SD大鼠经口灌胃给予三七药酒的重复给药毒性,指导三七药酒临床安全合理用药。方法 选用SPF级大鼠200只,随机分为5组,即空白对照组（纯水9 mL/kg）,白酒低、高剂量组（白酒3、9 mL/kg）,三七药酒低、高剂量组（三七药酒3、9 mL/kg）,每组40只,雌雄各半。每天给药1次,连续给药26周,停药后恢复观察4周。检测指标包括一般观察、摄食、体重、眼科及尿液检查、血液学检查、生化学检查、主要脏器称量和脏器系数计算、组织病理学检查。结果 三七药酒大鼠每次给药后出现活动减少、俯卧、无力（仅9 mL/kg剂量）、流涎（仅9 mL/kg剂量）。随着给药时间的延长,上述异常反应出现的时间和恢复时间逐渐缩短,停药即可恢复。9 mL/kg剂量给药期间雄性大鼠体重增长减缓、摄食量减少;各期检查眼科、尿液指标未见明显异常;9 mL/kg剂量雄鼠中性粒细胞、单核细胞升高,淋巴细胞降低;雌雄大鼠总蛋白（T.P）、白蛋白（ALB）、球蛋白（GLO）下降,雌鼠血糖（GLU）下降;雌鼠肝脏脏体系数升高。组织病理学检查显示三七药酒9 mL/kg剂量大鼠的毒性靶器官为肝脏和胃,与给予白酒9 mL/kg剂量后变化基本一致。3 mL/kg剂量大鼠未显示明显的毒性靶器官。上述异常指标有一定的剂量相关性和性别差异,停药4周后均恢复。结论 长期、大剂量、连续给予三七药酒可引起SD大鼠可逆性的肝脏和胃毒性。与相同剂量的白酒相比,三七药酒未见新的、更严重的毒性反应和毒性靶器官。

关键词: 三七药酒, 大鼠, 重复给药毒性, 肝脏, 胃

Abstract: Objective To observe the repeat-dose toxicity of Sanqi Yaojiu in rats．Methods Totally 200 SD rats (males and females)were randomly divided into 5 groups, namely blank control group (purified water),vehicle control groups (basic liquor 3, 9 mL/kg) and Sanqi Yaojiu group (3, 9 mL/kg), 40 in each group, half male and half female. All rats were administered intragastrically once a day for 6 months with 4-weeks recovery phase. Test indicators included general clinical observation, feeding, weight, ophthalmology and urine examination, hematology, biochemical examination, major organ weighing and organ coefficient, and histopathological examination. Animal necropsy was scheduled at 13 weeks, 26 weeks after administered and the end of the recovery period, respectively. Results After each administration, rats of Sanqi Yaojiu groups showed decreased activity, prone position, weakness (only 9 mL/kg) and salivation (only 9 mL/kg). As the time of administration was prolonged, the period of occurrence and recovery of the above abnormal reactions were gradually shortened, and the above abnormal reactions were recovered after withdrawal. For 9 mL/kg dose of Sanqi Yaojiu or basic liquor, the weight and food intake of male rats were decreased, the neutrophil and monocytes were increased and lymphocyte were decreased in male rats. T.P, ALB, GLO were decreased in male and female rats, and GLU was decreased in female rats. The liver coefficient increased in female rats. Histopathological examination showed that the toxic target organs of rats in the 9 mL/kg dose of Sanqi Yaojiu or basic liquor were liver and stomach, which were basically consistent with the dose of 9 mL/kg of liquor. Rats at 3 mL/kg dose did not show significant toxic target organs. The above abnormal indicators had a certain dose-related and gender differences, and recovered after 4 weeks of withdrawal. Conclusion Intragastric administration of Sanqi Yaojiu for 26 weeks at 9 mL/kg dose can induce reversible damage to liver and stomach in rats. Compared with the same dose of basic liquor, Sanqi Yaojiu did not show new, more serious toxic reactions and toxic target organs.

Key words: Sanqi Yaojiu, rat, repeat-dose toxicity, liver, stomach

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