中国药物警戒 ›› 2017, Vol. 14 ›› Issue (12): 730-736.

• 常用中药减毒研究专栏 • 上一篇    下一篇

补骨脂不同炮制方式对正常小鼠急性毒性实验比较研究

蔡涛涛1,黄娜娜2,王亮1,3,孙晓倩4,李晓宇1,3,孙蓉5*   

  1. 1山东中医药大学，山东 济南 250355；
    2山东大学齐鲁第二医院，山东 济南 250033；
    3山东省中医药研究院，山东 济南 250014；
    4山东大学药学院，山东 济南 250012；
    5山东大学齐鲁医学院，山东 济南 250012
  • 收稿日期:2017-12-11 修回日期:2018-01-19 出版日期:2017-12-20 发布日期:2018-01-19
  • 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:蔡涛涛，男，在读硕士，中药药理与毒理。
  • 基金资助:
    国家公益性行业科研专项（201507004-03）：临床常见中药朱砂、补骨脂、决明子的配伍减“毒”研究；山东省泰山学者工程专项经费资助（ts201511107）。

Experimental Comparison Study on Acute Toxicity of Different Processing Methods of Psoraleae Fructus on Normal Mice

CAI Tao-tao1, HUANG Na-na2 ,WANG Liang1,3, SUN Xiao-qian4 , LI Xiao-yu1,3, SUN Rong5*   

  1. 1Shandong University of Traditional Chinese Medicine, Shandong Jinan 250355, China;
    2The Second Hospital of Shandong University, Shandong Jinan 250033, China;
    3Shandong Academy of Chinese Medicine, Shandong Jinan 250014, China;
    4School of Pharmaceutical Sciences of Shandong University, Shandong Jinan 250012, China;
    5Cheeloo College of Medicine, Shandong University, Shandong Jinan 250012, China
  • Received:2017-12-11 Revised:2018-01-19 Online:2017-12-20 Published:2018-01-19

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摘要： 目的 比较不同炮制方式对补骨脂的正常小鼠急性毒性影响。方法 根据中国药典2015年版盐炙法制备盐补骨脂。8倍量水提取3次，每次1 h，制备生补骨脂和盐补骨脂的水提组分，粉碎药物，粉末过120目筛，制备生补骨脂和盐补骨脂的全组分，采用HPLC法、经典急性毒性实验法，进行补骨脂上述样品中补骨脂素和异补骨脂素的含量测定及正常小鼠急性毒性比较研究。结果 生补骨脂全组分、盐补骨脂全组分、生补骨脂水提组分、盐补骨脂水提组分中补骨脂素百分含量分别为0.398 0%、0.481 3%、0.073 9%、0.072 7%，异补骨脂素百分含量分别为0.364 6%、0.454 1%、0.056 5%、0.051 1%。生补骨脂和盐补骨脂水提组分半数致死量（LD50）与95%可信限为49.212 g·kg-1·d-1（47.773～50.696 g·kg-1·d-1）和56.028 g·kg-1·d-1（54.074～58.067 g·kg-1·d-1），分别相当于临床70 kg的成人每kg体重日用量的 344.5倍、392.2倍。生补骨脂和盐补骨脂全组分最大给药量（MFD）为40.032 g·kg-1·d-1和31.560 g·kg-1·d-1，分别相当于临床70 kg的成人每kg体重日用量的280.2、220.9倍。小鼠急性毒性症状主要有精神不佳、怠动、俯卧昏睡、抽搐、走路不稳。结论 补骨脂不同炮制方式对小鼠急性毒性强度为：生补骨脂水提组分>盐补骨脂水提组分>盐补骨脂全组分>生补骨脂全组分，不同炮制方式补骨脂中补骨脂素与异补骨脂素含量越高，对正常小鼠急性毒性强度越大，提示补骨脂的毒性大小与补骨脂素和异补骨脂素含量高低呈正相关，其毒性物质基础、毒性作用特点及毒性作用机制还需进一步研究。

关键词: 补骨脂, 小鼠, 急性毒性

Abstract: Objective To compare the acute toxicity of Psoraleae Fructus in normal mice prepared by different processing methods. Methods The method of preparing salt-processed Psoraleae Fructus was according to salt process of the Chinese Pharmacopoeia 2015. The water extracts of raw Psoraleae Fructus and salt-processed Psoraleae Fructus were prepared by extraction with 8 times the amount of water three times for 1 hour each. The all components of raw Psoraleae Fructus and salt-processed Psoraleae Fructus were prepared by crushing and making powder through 120 mesh sieve. HPLC method and the classical method of acute toxicity were used to determine the content of psoralen and isopsoralen and the acute toxicity in the above samples, and compare the content and the acute toxicity. Results The content of psoralen on the water extracts of raw Psoraleae Fructus and salt-processed Psoraleae Fructus was separately 0.0739%, 0.0727%, the content of psoralen on all components of raw Psoraleae Fructus and salt-processed Psoraleae Fructus was separately 0.3980%, 0.4813%, and the content of isopsoralen in the above samples was separately 0.0565%, 0.0511%, 0.3646%, 0.4541%. The LD50 and 95% confidence limit of water extraction components in raw Psoraleae Fructus and salt-processed Psoraleae Fructus are 49.212 g·kg-1·d-1(47.773～50.696 g·kg-1·d-1) and 56.028 g·kg-1·d-1(54.074～58.067 g·kg-1·d-1), which was respectively equal to 344.5 times and 392.2 times of the clinical daily dosage in 70 kg humans. The MFD of all components in raw Psoraleae Fructus and salt-processed Psoraleae Fructus was 40.032 g·kg-1·d-1 and 31.560 g·kg-1·d-1, which was respectively equal to 280.2 times and 220.9 times of the clinical daily dosage in 70 kg humans. The main acute toxicity symptoms and signs are poor spirit, negligent action, prostrate motionlessness, convulsions and unsteady walk. Conclusion The acute toxicity intensity in Psoraleae Fructus by different processing methods on normal mice is: water extraction components in raw Psoraleae Fructus > water extraction components in salt-processed Psoraleae Fructus > all components in salt-processed Psoraleae Fructus > all components in raw Psoraleae Fructus, The acute toxicity intensity of Psoraleae Fructus prepared by different processing methods in normal mice increases with increasing content of psoralen and isopsoralen, suggesting that there is a positive correlation between the toxicity and content of psoralen and isopsoralen, the toxic substances, toxicity characteristics and toxicity mechanism are all to be further studied.

Key words: Psoraleae Fructus, mice, acute toxicity

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