中国药物警戒 ›› 2022, Vol. 19 ›› Issue (5): 510-514.
DOI: 10.19803/j.1672-8629.2022.05.08

• 荆防颗粒安全性研究专栏 • 上一篇    下一篇

荆防颗粒浸膏大鼠90天重复灌胃给药毒性研究

徐百卉, 王恩力, 郑成成, 徐娇艳, 李贝贝, 张晓红, 周宗仪, 王永刚, 姚景春*   

  1. 鲁南制药集团股份有限公司新药安评中心, 中药制药共性技术国家重点实验室,临沂市天然药物免疫药理毒理重点实验室,山东 临沂 273400
  • 收稿日期:2022-01-19 出版日期:2022-05-15 发布日期:2022-05-18
  • 通讯作者: *姚景春,男,硕士,研究员,新药临床前药理毒理学。E-mail：yaojingchun@lunan.com
  • 作者简介:徐百卉,女,硕士,工程师,生理学。
  • 基金资助:
    国家重点研发计划（2019YFC1711205）

Toxicity of Jingfang granule extractum by 90 days repeated ingastric administration in rats

XU Baihui, WANG Enli, ZHENG Chengcheng, XU Jiaoyan, LI Beibei, ZHANG Xiaohong, ZHOU Zhongyi, WANG Yonggang, YAO Jingchun*   

  1. Center For Drug Safety Evaluation of Lunan Pharmaceutical Group Corporation, State Key Laboratory of Generic Manufacture Technology of Chinese Traditional Medicine, Linyi Key Laboratory of Immunopharmacology and Toxicology of Natural Drugs, Linyi Shandong 273400, China
  • Received:2022-01-19 Online:2022-05-15 Published:2022-05-18

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摘要： 目的 观察SD 大鼠灌胃给予荆防颗粒浸膏的重复给药毒性,指导荆防颗粒临床安全合理用药。 方法 选用SPF 级大鼠144 只,随机分为4 组,即空白对照组（注射用水0 g·kg-1·d-1）,荆防颗粒浸膏1、3、10 g·kg-1·d-1 剂量组,每组36 只,雌雄各半。每日灌胃给药1 次,连续给药90 d,停药后恢复观察30 d。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 SD 大鼠按照1、3、10 g·kg-1·d-1 剂量重复灌胃荆防颗粒浸膏90 d 后,1、3 g·kg-1·d-1 剂量组未引起动物的一般状态、摄食量、体重、血液学、血液生化学和组织病理学的异常改变;10 g·kg-1·d-1 剂量组雄鼠摄食量降低,体重增长缓慢,组织病理学检查可见大鼠早期慢性进行性肾病发生率升高,上述效应在恢复期结束后均恢复正常。 结论 SD 大鼠90 d 重复灌胃荆防颗粒浸膏的无明显毒副反应剂量（NOAEL）为3 g·kg-1·d-1,有毒剂量为10 g·kg-1·d-1,该剂量下荆防颗粒浸膏引起动物食欲减退及慢性进展性肾炎（CPN）发生率提高,考虑到人没有与CPN 相对应的疾病,由此谨慎地推断最严重的情况下该剂量荆防颗粒浸膏会存在潜在的轻微肾损伤。上述效应在恢复期结束后均恢复,表明荆防颗粒浸膏导致的不良反应具有可逆性。

关键词: 荆防颗粒浸膏, 大鼠, 灌胃, 给药毒性, 肾

Abstract: Objective To observe the repeat-dose toxicity of Jingfang granule extractum in rats, to as to guide the safe and rational use of Jingfang granules in clinic. Methods Totally 144 SPF rats were randomly divided into 4 groups, namely blank control group (0 g·kg-1·d-1 of water for injection), Jing Fang granule extractum 1, 3, 10 g·kg-1·d-1, with 36 rats in each group and half male and half female. All rats were administered intragastrically once a day for 90 days with 30 days 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. Results After 90 days of repeated intragastric administration of Jingfang granule extractum at doses of 1, 3 and 10 g·kg-1·d-1, there were no abnormal changes in general state, food intake, body weight, hematology, blood biochemistry and histopathology. At the dose of 10 g·kg-1·d-1, male rats had lower food intake and slower body weight gain, and histopathological examination showed an increased incidence of early chronic progressive kidney disease, all of which returned to normal after the recovery phase. Conclusion The non-toxic dose (NOAEL) of Jingfang granule extractum is 3 g·kg-1·d-1 and the toxic dose was 10 g·kg-1·d-1. Under this dose, Jingfang granule extractum can cause anorexia and increase the incidence of chronic progressive nephritis (CPN) in animals. Considering that there is no disease corresponding to CPN in human, It is prudent to conclude that at the most severe dose, there is a potential for minor kidney injury. The above effects are recovered after the end of the recovery phase, which indicating that the adverse reactions caused by Jingfang granule extractum are reversible.

Key words: Jingfang granule extractum, rat, intragastric administration, toxicity, kidney

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