中国药物警戒 ›› 2012, Vol. 9 ›› Issue (4): 193-197.

• 基础及临床研究 •    下一篇

艾叶不同组分对小鼠镇痛及伴随毒副作用研究

王会1，黄伟2，迟雪洁3，张亚囡1，孙蓉2，*   

  1. 1 山东中医药大学，山东 济南 250355；
    2 山东省中医药研究院，山东 济南 250014；
    3 天津中医药大学，天津 300193
  • 收稿日期:2011-09-05 出版日期:2012-04-10 发布日期:2015-08-10
  • 通讯作者: 孙蓉,女,研究员,硕士生导师,中药药理与毒理。E-mail：sunrong107@163.com
  • 作者简介:王会，女，硕士研究生，中药药理与毒理。
  • 基金资助:
    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课题2（2009CB522802）,山东省科技平台建设项目课题（2008GG2NS02021）

Study on the Toxicity and Side-effects Accompanied with Analgesic Effect of Different Components from Folium Artemisiae Argyi in Mice

WANG Hui1, HUANG Wei2, CHI Xue-jie3, ZHANG Ya-nan1, SUN Rong2, *   

  1. 1 Shandong University of Traditional Chinese Medicine, Shandong Jinan 250355, China;
    2 Shandong Research Academy of TCM, Shandong Jinan 250014, China;
    3 Tianjin University of Traditional Chinese Medicine; Tianjin 300193, China
  • Received:2011-09-05 Online:2012-04-10 Published:2015-08-10

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摘要： 目的研究细胞色素P450酶2C9(CYP2C9)及维生素K环氧化物还原酶复合体亚单位1（VKORCl）基因多态性对中国肺栓塞患者华法林维持剂量的影响。方法对108例INR已稳定达标的中国肺栓塞患者，采用TaqMan MGB探针法，检测CYP2C9*2、*3位点和VKORC1-1639A>G位点基因型。记录患者的年龄、性别、体重、身高及华法林日平均剂量。结果VKORC1 -1639AG或GG基因型患者华法林稳定日均剂量明显高于AA基因型患者（5.81±1.93 vs 3.33±1.11mg，P <0.001）;CYP2C9*2或*3变异的患者华法林稳定日均剂量低于无变异的患者（2.57±1.31 vs 3.97±1.67mg，P<0.001）;包括患者性别、年龄、身高、体重、CYP2C9和VKORC1基因型等因素在内的华法林稳定剂量预测模型可解释51.1%左右的华法林稳定剂量个体差异（R2=0.511，P <0.001）。结论CYP2C9和VKORC1基因型检测对指导中国肺栓塞患者个体化应用华法林有一定的临床意义。

关键词: 华法林, 肺栓塞, 稳定剂量, CYP2C9, VKORC1, 基因多态性

Abstract: Objective To determine the material basis of the volatile oil and water extracts from Folium Artemisia Argyi, the effective dose range and time range as well as the dose range and the time window occurred with side effects, to lock the target organ of toxicity, in order to provide the experimental data for clinical safety. MethodsAnalgesic effect of the volatile oil and water extracts from Folium Artemisia Argyi were investigated by hot plate test and acetic acid writhing test in mice. The symptoms of mice were observed, the ratios of liver and kidney were calculated, and the levels of ALT, AST, BUN and Cr in blood were detected, for the purpose of inspecting the side effects of the volatile oil and water extracts. ResultsThere were significant differences in the value of hot-plate pain threshold and frequency of the writhing test of each dose group after 1、3 、7 days administration to mice, and there were certain time and dosage dependence relationships, and the analgesic effect of water extracts components was stronger than volatile oil. The indexes detection in serum showed that different dosage group had different increase in the level of ALT、AST、Cr、BUN and the ratio of liver and kidney, and there were certain time and dosage dependence relationships, and the toxicity of volatile oil was stronger than water extracts components. ConclusionThe volatile oil and water extracts from Folium Artemisia Argyi showed certain effect of analgesia, the effective range of analgesia were respectively(34.5 g·kg-1~138 g·kg-1) and (1.17 g·kg-1~4.68 g·kg-1), and showed certain dose-effect and time-effect relationship, and calculated by equivalent amount of crude drug, the analgesic effect of volatile oil was stronger than water extracts components. The side-effects accompanied with analgesic effect were liver function, renal function and viscera indexs, the hepatotoxical injury in particular. The dose ranges of the volatile oil and water extracts produced liver toxicity were(34.5 g·kg-1~138 g·kg-1) and(2.34 g·kg-1~4.68 g·kg-1), it showed certain dose-dependent and time-dependent relationship; while the dose ranges of the volatile oil and water extraction component produced kidney toxicity were(69.0 g·kg-1~138 g·kg-1) and (2.34 g·kg-1~4.68 g·kg-1). At present the Pharmacopoeia recommends that the amount of Folium Artemisia Argyi is 3-9g; as there has been hepatotoxicity and renaltoxicity when the animals were administrated for 7 days, which should be attended in clinical application.

Key words: Folium Artemisia Argyi, analgesia, toxicity