河豚毒素与阿斯匹林联合应用对醋酸所致小鼠扭体反应和福尔马林致痛实验的影响

河豚毒素与阿斯匹林联合应用对醋酸所致小鼠扭体反应和福尔马林致痛实验的影响

徐英^*, 库宝善, 耿兴超, 姚海燕, 张永鹤, 韩继生, 齐世荃

1.北京大学医学部基础医学院药理学系, 北京 100083;
2.南宁枫叶药业有限公司, 广西南宁 530012

收稿日期:2004-05-17 修回日期:2005-08-10 出版日期:2005-09-15 发布日期:2005-09-15
通讯作者: 徐英*

Analgesic Effects of Tetrodotoxin Combined with Acetylsalicylic Acid on Acetic Acid-induced Abdominal Constriction and Formalin Test in Mice

XU Ying^*, KU Bao-shan, GENG Xing-chao, YAO Hai-yan, ZHANG Yong-he, HAN Ji-sheng, QI Shi-quan

1.Department of Pharmacology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100083, China;
2.Nanning Ample Leaf Pharmaceutical Co. Ltd. Nanning 530012, China

Received:2004-05-17 Revised:2005-08-10 Online:2005-09-15 Published:2005-09-15
Contact: XU Ying*

摘要/Abstract

摘要：

目的探讨河豚毒素与阿斯匹林联合应用是否具有协同镇痛效应。方法采用醋酸扭体实验和福尔马林致痛实验,小鼠分别肌肉注射河豚毒素、阿斯匹林及两者的混合物(0.39 μg·kg^-1, 0.79 μg·kg^-1加不同浓度的阿斯匹林), 观察联合用药是否具有协同镇痛作用。结果在两种镇痛实验中, 河豚毒素和阿斯匹林单独应用, 均具有一定的镇痛效应。在醋酸扭体实验中, 两药的ID50s分别为2.1 μg·kg^-1和64 mg·kg^-1; 在福尔马林致痛实验中, 两药能明显缩短皮下注射甲醛后第2时相小鼠舔脚时间, ID50s分别为2.3μg·kg-1和74.2mg·kg^-1。河豚毒素与阿斯匹林联合应用具有协同镇痛作用:(1)与单独应用阿斯匹林相比, 河豚毒素0.39μg·kg-1(150 LD50)、0.79 μg·kg^-1 (12/5 LD50)与阿斯匹林联合应用, 分别使阿斯匹林的镇痛ID50从64.0 mg·kg^-1下降到12.6 mg·kg^-1和5.8 mg·kg^-1 (醋酸扭体实验); 从74.2 mg·kg^-1下降到13.0 mg·kg^-1和7.4 mg·kg^-1(福尔马林致痛实验)。(2)协同效应图分析显示两者具有明显协同作用。结论河豚毒素与阿斯匹林联合应用具有协同镇痛效应, 本研究对于开发新型镇痛药具有一定的指导意义。

关键词: 河豚毒素, 河豚毒素, 河豚毒素, 阿斯匹林, 阿斯匹林, 阿斯匹林, 福尔马林, 福尔马林, 福尔马林, 半数抑制量ID50s, 半数抑制量ID50s, 半数抑制量ID50s, 镇痛作用, 镇痛作用, 镇痛作用, 协同作用, 协同作用, 协同作用

Abstract: Aim To study the effects of tetrodotoxin (TTX) combined with acetylsalicylic acid (ASA) on nociceptive stimulus in mice. Methods To assess the antinociceptive effects of TTX, ASA or TTX plus ASA, the acetic acid-induced abdominal constriction test and formalin pain test were used. Results TTX (0.5-4.0 μg·kg^-1 ) or ASA (25-200 mg·kg^-1) im produced a significant inhibition of acetic acid-induced abdominal constriction. The median inhibitory doses (ID50s) were 2.1 μg·kg^-1 for TTX and 64 mg·kg^-1 for ASA. TTX and ASA also showed a dose-dependent inhibition of the second phase response in the formalin pain model, the ID50s being 2.3 μg·kg^-1 and 74.2 mg·kg^-1, respectively. The interaction between TTX and ASA was synergistic, as evidenced by the fact that (1) when ASA alone compared with the combination of TTX (0.79 μg·kg^-1 or 0.39 μg·kg^-1) and ASA, the ID50s of ASA reduced from 64.0 mg·kg^-1 to 5.8 mg·kg^-1 or 12.6 mg·kg^-1, and from 74.2 mg·kg^-1 to 7.4 mg·kg^-1 or 13.0 mg·kg^-1 on the two models of nociceptive tests, respectively; and that (2) synergism in the analgesic effects was shown by isobiolographic analysis. Conclusion TTX, ASA and the combination of the two drugs produce analgesic effects in acetic acid-induced abdominal constriction test and formalin-induced pain test. The interactions between TTX and ASA may be useful in developing novel analgesic agents.

Key words: tetrodotoxin, tetrodotoxin, acetylsalicylic acid, acetylsalicylic acid, formalin, formalin, the median inhibitory doses ID50s, the median inhibitory doses ID50s, analgesic effect, analgesic effect, synergism, synergism

中图分类号:

R965

R971.1

Supporting: ^*Corresponding author. Tel.: 86-10-82801462

徐英^*, 库宝善, 耿兴超, 姚海燕, 张永鹤, 韩继生, 齐世荃. 河豚毒素与阿斯匹林联合应用对醋酸所致小鼠扭体反应和福尔马林致痛实验的影响[J]. .

XU Ying^*, KU Bao-shan, GENG Xing-chao, YAO Hai-yan, ZHANG Yong-he, HAN Ji-sheng, QI Shi-quan. Analgesic Effects of Tetrodotoxin Combined with Acetylsalicylic Acid on Acetic Acid-induced Abdominal Constriction and Formalin Test in Mice[J]. .

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