摘要
目的 在动物疼痛模型上，观察泰国眼镜蛇长链突触后α-神经毒素cobratoxin（CTX）的化学修饰物receptin（REC）的镇痛作用及其阿托品和纳洛酮对其镇痛作用的影响。方法 采用腹腔注射（i．p．，5mg/kg，7．07mg/kg，10mg/kg）或脑室注射（i．c.v．，62．5g/kg）的方法给予REC；采用小鼠热板反应、扭体反应及大鼠甩尾反应试验研究药物的镇痛作用；应用预先给予阿托（atropine，Atr；0．5mg／kg，i．m．或10mg／kg，i．p．）或纳洛酮（naloxone，Nal；3mg／kg，i．p．）研究胆碱能及阿片肽能神经在REC镇痛中的作用；采用mnilnex试验观察REC对小鼠自发活动的影响。结果 REC（5mg／kg，7．07mg/kg及10mg/kg，i．p．）在小鼠热板试验及扭体试验中均呈现出剂量依赖性镇痛作用，并于给药后20小时出现显著镇痛作用。在大鼠甩尾试验中，REC62．5mg/kg（相当于全身给药的1／160，i．c.v．）后产生显著镇痛作用。阿托品或纳洛酮不能阻断REC的镇痛作用。高剂量REC（10mg／kg，i．p．）对小鼠的自发活动无明显影响。结论 REC具有镇痛作用，尽管中枢神经系统参与REC的镇痛作用，但外周神经系统可能亦介导REC的镇痛作用。中枢胆碱能及阿片肽能神经系统可能不参与REC的镇痛作用。
Objective To investigate the analgesia induced by receptin （REC）, a chemically modified cobratoxin （CTX, a long-chain postsynaptic α-neurotoxin from Thailand cobra venom）, and the effects of atropine and naloxone on antinociceptive activity of REC in rodent pain models. Methods REC was administered intraperitoneally （5 mg/kg, 7.07 mg/kg, or 10 mg/kg, i.p.） or intra-cerebral venticularly （62.5 μg/kg, i.c.v.）. The antinociceptive action was determined using the hotlate test, the acetic acid writhing test and tail flick assay in mice and rats. The involvement of cholinergic and the opioid peptidergic systems in REC-induced analgesia were examined by pretreatment of animals with atropine （Atr; 0.5 mg/kg, i.m. or 10 mg/kg, i.p.） or naloxone （Nal; 3 mg/kg, i.p.）. The effect of REC on motor activity was tested using the Animex test in mice. Results REC （5 mg/kg, 7.07 mg/kg or 10 mg/kg, i.p.） exhibited a dose-dependent analgesic action in mice as determined with hot-plate test and acetic acid writhing test. The significant analgesia of REC was seen 2 h to 3 h after its administration. In the rat-tail flick assay, the administration of REC at 62.5 μg/kg （1/160 of systemic dose; i.c.v.）produced marked analgesic effects. Atropine at 0.5 mg/kg （i.m.）, 10 mg/kg （i.p.） or naloxone at 3 mg/kg （i.p.） failed to block the analgesic effects of REC. REC at the highest effective dose of 10 mg/kg did not change the spontaneous mobility of mice. Conclusion These results demonstrate that REC has analgesic effect. This activity appears to be mediated through the peripheral nervous system though central nervous system may contribute to REC＇s analgesic effects. The central cholinergic system and opioid peptidergic system appear not to be involved in the antinociceptive action of REC.
