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目的 :研究组胺H3受体拮抗剂ciproxifan(CPF)在小鼠痛觉传导调节过程中的作用及其机制。方法 :用 3种不同的小鼠痛觉模型 (热板法、扭体法和福尔马林实验 )观察CPF的镇痛作用。同时用特异性组胺脱羧酶 (HDC)抑制药α 氟甲基组胺酸 (α FMH) ,观察组胺在CPF发挥镇痛效应过程中所起的作用。在福尔马林致痛模型中 ,还测定了小鼠脑、脊髓和血清中一氧化氮 (NO)和前列腺素E2(PGE2 )的含量。结果 :热板实验中 ,CPF 1mg·kg- 1和 3mg·kg- 1能明显延长小鼠的痛反应时间 ,其镇痛作用从用药后 2 0min开始 ,可持续 6 0min以上。扭体实验中 ,CPF 1mg·kg- 1可明显抑制小鼠的扭体次数 ,最高抑制率达 4 9.85 %。皮下注射福尔马林能引起 2个时相 (Ⅰ相、Ⅱ相 )的痛反应。这种由福尔马林引起的 2个时相的痛反应均可明显被CPF 0 .3,1,3mg·kg- 1抑制。在 3种致痛模型中 ,CPF的镇痛效应均可被α FMH 5 0mg·kg- 1逆转。使用福尔马林后 ,小鼠脑和脊髓中NO和PGE2 水平升高 ,而CPF能明显抑制这种升高作用 ,该抑制作用不被α FMH所拮抗。但CPF对血清中NO和PGE2 的浓度没有影响。结论 :组胺H3受体拮抗药CPF对多种性质刺激引起的疼痛均有镇痛作用 ,对福尔马林引起的炎性疼痛和非炎性疼痛都有效。CPF的这种镇痛作用可能与其促进?
AIM: To investigate the role and mechanism of ciproxifan (CPF), a histamine H3 receptor antagonist, in the regulation of pain-mediated conduction in mice. Methods: The analgesic effects of CPF were observed using three different mouse models of pain (hot plate method, writhing method and formalin test). At the same time, the specific histamine decarboxylase (HDC) was used to inhibit α-FMH. The effect of histamine on the analgesic effect of CPF was observed. In the formalin-induced pain model, the levels of nitric oxide (NO) and prostaglandin E2 (PGE2) in the brain, spinal cord and serum of mice were also determined. Results: In the hot plate experiment, CPF 1 mg · kg-1 and 3 mg · kg-1 significantly prolonged the pain response time of mice. The analgesic effect started at 20 min after the administration and lasted for more than 60 min. In writhing experiment, CPF 1 mg · kg-1 significantly inhibited the number of writhing in mice with the highest inhibition rate of 4 9.85%. Subcutaneous injection of formalin caused two phase (phase Ⅰ, phase Ⅱ) pain response. The pain response of the two phases caused by formalin was significantly inhibited by CPF 0.3, 1.3, mg · kg -1. The analgesic effect of CPF was reversed by α FMH 50 mg · kg -1 in all three models of pain. After formalin administration, NO and PGE2 levels were increased in the brain and spinal cord of mice, whereas CPF significantly inhibited this elevation and the inhibitory effect was not antagonized by α FMH. However, CPF had no effect on serum NO and PGE2 concentrations. Conclusion: Histamine H3 receptor antagonist CPF has analgesic effects on pain caused by various stimuli and is effective on both inflammatory pain and non-inflammatory pain induced by formalin. This analgesic effect of CPF may be related to its promotion?