甲基丁香酚镇痛抗炎作用及机制研究

Study of Antinociceptive and Anti-inflammatory Effect and Antinociceptive Mechanism of Methyleugenol

目的甲基丁香酚是细辛挥发油的主要成分之一,对甲基丁香酚镇痛抗炎效果进行评价,探索其镇痛作用机制。方法本研究以醋酸刺激痛、福尔马林刺激痛、热刺激痛实验和二甲苯致小鼠耳肿胀实验评价甲基丁香酚的镇痛、抗炎作用,并以受体阻断实验、一氧化氮(NO)检测实验探讨其镇痛作用机制。结果 (1)甲基丁香酚(6,3,1.5 mg·kg^(-1)),在醋酸刺激痛实验中,显著抑制小鼠扭体次数,抑制率分别为56.58%,51.25%,40.93%;在福尔马林刺激痛实验中,缩短Ⅱ相舔足、咬足时间,抑制率分别为56.62%,47.03%,33.98%;在热刺激痛实验中明显延长小鼠热痛潜伏期,在2 h镇痛作用达高峰,痛阈提高率分别为57.32%,42.14%,26.29%。(2)甲基丁香酚(6,3,1.5 mg·kg^(-1))明显抑制二甲苯所致小鼠耳肿胀,抑制率分别为76.43%,57.23%,35.00%。(3)受体阻断实验显示甲基丁香酚(6 mg·kg^(-1))镇痛作用可被GABA_A受体阻断剂荷包牡丹碱(3 mg·kg^(-1))阻断,不能被阿片受体阻断剂纳洛酮(3 mg·kg^(-1))阻断。NO检测实验显示甲基丁香酚(6 mg·kg^(-1))可抑制醋酸致痛小鼠血清NO水平。结论本研究表明细辛挥发油成分甲基丁香酚有明显镇痛抗炎作用,其镇痛作用机制与激动GABAA受体,抑制NO水平相关。

Objective To evaluate the antinociceptive and anti-inflammatory effect of methyteugenol, a compound derived from Herba Asari, and to further explore the possible antinociceptive mechanism of methyleugenol. Methods Acetic acid-induced writhing test, hot-plate-induced pain test, formalin-induced patin test and xylene induced auricular edema test were performed for the evaluation of antinociceptive and anti-inflammatory effect. And receptor block tests and nitric oxide（NO） assay kit were used for the exploration of antinociceptive mechanism. Results The results showed that methyleugenol at the doses of 6, 3, 1.5 mg/kg inhibited the acetic acid-induced writhing by 57 %, 51%, 41% in the acetic acid-induced writhing test, reduced the phase ]I time for licking or biting the injected paw by 57 %, 47 %, 34 % in the formalin-induced pain test, significantly prolonged the latency time （pain peak arriving at hour 2） with the increase of pain threshold by 57 %, 42 % and 26 % in the hot-plate-induced pain test, and inhibited the auricular edema by 76 %, 57 %, 35 % in the xylene-induced mouse auricular edema test. Furthermore, the results showed that the antinociceptive effects of methyleugenol （6 mg·kg^-l） were blocked by Bicuculline （a GABAA receptor antagonist, 3 mg·kg^-1） in the hot-plate-induced pain test and acetic acid-induced writhing test, but could not be blocked by naloxone （an opioid receptor antagonist, 3 mg·kg^-1）. The serum level of NO elevated by acetic acid injection could be inhibited by methyleugenol （6 mg·kg^-1）. Conclusion This study showed that methyleugenol had significant antinociceptive and anti-inflammation effect, and the mechanism is probably related to the activation of GABAA receptor and inhibition of NO level.