中国药物警戒 ›› 2021, Vol. 18 ›› Issue (5): 427-432.
DOI: 10.19803/j.1672-8629.2021.05.06

• 临床常见中药补骨脂、决明子配伍减毒研究专栏 • 上一篇    下一篇

青娥丸及不同拆方组合水提物对正常小鼠急性毒性影响的实验研究

郭欣1,2, 蔡涛涛1,3, 黄娜娜1, 孙蓉1,4,*   

  1. 1山东大学第二医院,山东 济南 250033;
    2天津中医药大学,天津 301617;
    3潍坊市中医院,山东 潍坊 261000;
    4山东大学高等医学研究院,山东 济南 250012
  • 收稿日期:2020-12-21 出版日期:2021-05-15 发布日期:2021-05-12
  • 通讯作者: *孙蓉,女,教授·博导,中药药理与毒理。E-mail:sunrong107@163.com
  • 作者简介:郭欣,女,博士,中药药理学与创新药发现。
  • 基金资助:
    国家自然基金面上项目（81773997）;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);国家公益性行业科研专项（201507004-03）;泰山学者工程专项经费项目（Ns201511107）

Experimental Study on Acute Toxicity of Qing 'e Pills and Their Separated Prescriptions Aqueous Extract in Normal Mice

Guo Xin1,2, Cai Taotao1,3, HUANG Nana1, Sun Rong1,4,*   

  1. 1The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan Shandong 250033, China;
    2Tianjin University of Traditional Chinese Medicine (TCM), Tianjin 300193, China;
    3Weifang Hospital of Traditional Chinese Medicine, Weifang Shandong 261000, China;
    4Adva-nced Medical Research Institute, Cheeloo College of Medicine, Shandong University, Jinan Shandong 250012, China
  • Received:2020-12-21 Online:2021-05-15 Published:2021-05-12

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摘要： 目的 通过比较青娥丸及不同拆方组合水提物对正常小鼠急性毒性影响,探讨青娥丸组方配伍规律,为临床合理使用该方提供实验依据。方法 根据经典的“君臣佐使”组方原则和中药“七情”配伍及性味、主治理论,将青娥丸拆分为组合1（盐杜仲+盐补骨脂+炒核桃仁）、组合2（盐杜仲+盐补骨脂）、组合3（盐补骨脂+大蒜）、组合4（盐补骨脂+炒核桃仁+大蒜）、组合5（青娥丸全方）;制备青娥丸不同拆方水提物,采用高效液相色谱法（HPLC）检测各药物组补骨脂素和异补骨脂素的含量;运用经典急性毒性实验方法进行青娥丸及不同拆方组合水提物对正常小鼠急性毒性实验比较研究。结果 组合1、组合2、组合3、组合4、组合5水提物中补骨脂素含量依次为0.156 3%、0.172 6%、0.104 8%、0.050 3%、0.083 8%;异补骨脂素含量依次为0.160 6%、0.158 9%、0.096 0%、0.0366 0%、0.062 3%。各组最大耐受量（MTD）值依次为165.32、156.52、156.00、118.78、129.84 g/(kg·d),分别相当于临床70 kg人每公斤体重日用量的779.77、892.94、1 779.6、956.8、538.59倍。小鼠毒性症状主要有精神不佳、怠动、共济失调、僵住、俯卧、阵挛性惊厥,各组小鼠出现不同程度的耳部、尾部及眼部红肿症状。结论 上述各组合急性毒性均小于实验室前期报道的盐补骨脂的急性毒性,提示按照中医组方结构进行配伍的青娥丸不同拆方组合均能减轻盐补骨脂的急毒程度,印证了中医配伍在安全性控制上的科学性与合理性,其配伍减毒机制有待后续深入研究。

关键词: 青娥丸, 配伍减毒, 盐补骨脂, 急性毒性, 正常小鼠, 水提物

Abstract: Objective To compare the acute toxicity of Qing'e pills and their separated prescriptions aqueous extract in mice and to explore the mechanism of prescription compatibility so as to provide data for safe and rational drug use in clinic. Methods According to the classical principle of "monarch, minister, assistant and guide" and the seven-emotion compatibility of Chinese medicine, as well as the theory of nature, taste and indications, Qing'e pills were divided into five groups: combination 1 (salt Eucommia ulmoides Oliver+salt Psoralea corylifolia L+fried Juglans regia L.), combination 2 (salt Eucommia ulmoides Oliver+salt Psoralea corylifolia L), combination 3 (salt Psoralea corylifolia L + Alliumsativum L.), combination 4 (salt Psoralea corylifolia L+fried Juglans regia L. + Alliumsativum L.), and combination 5 (Qing'e pills). The aqueous extract of Qing'e pills was prepared, and the contents of psoralen and isopsoralen in each drug group were detected by HPLC. The classical experimental method for acute toxicity was used to compare the difference in acute toxicity between Qing'e pills and their separated prescriptions aqueous extract. Results The contents of psoralen in the water extracts of combination 1, combination 2, combination 3, combination 4 and combination 5 were 0.156 3%, 0.172 6%, 0.104 8%, 0.050 3% and 0.083 8% respectively, compared with 0.160 6%, 0.158 9%, 0.096 0%, 0.036 6% and 0.062 3% respectively for isopsoralen. The maximum tolerated dose (MTD) value of each group was 165.32, 156.52, 156.00, 118.78 and 129.84 g/(kg·d),respectively, which were equivalent to 779.77, 892.94, 1779.6, 956.8 and 538.59 times the daily dosage per kilogram of body weight of 70 kg people. The main toxic symptoms of mice were depression, inactivity, ataxia, stiffness, and proneness to clonic convulsion. The mice in each group had different degrees of redness and swelling in ears, tails and eyes. Conclusion The acute toxicity of combinations mentioned above is not so severe as that of salt Psoralea corylifolia L, suggesting that the prescriptions of Qing 'e pills combined according to the prescription structure of traditional Chinese medicine can reduce the acute toxicity of Psoralea corylifolia L. The compatibility of traditional Chinese medicine can ensure effective safety control. The mechanism of detoxification needs to be further studied.

Key words: Qing'e pills, compatibility and toxicity reduction, salt Psoralea corylifolia L., acute toxicity, normal mice, aqueous extract

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