一氧化氮介导的呱氨托美汀镇痛作用机理

ANTINOCICEPTION MECHANISM OF AMTOLMETIN GUACYL MEDIATED BY NITRIC OXIDE IN MICE

目的:探讨一氧化氮(nitric oxide,NO)介导的呱氨托美汀(Amtolmetin Guacyl,AMG)镇痛作用机理。方法:利用AMG对冰醋酸(AA)扭体小鼠的镇痛作用;测定其脊髓、脑和血液的NO2-,一氧化氮合酶(nitric oxide synthase,NOS)含量。L-Arg,L-NAME对AMG在AA与福尔马林(FA)致痛小鼠的镇痛作用;测定L-Arg,L-NAME对AMG在AA扭体镇痛小鼠脊髓、脑和血液的NO2-含量。结果:在AMG对AA扭体致痛小鼠镇痛作用中,AMG大剂量(300 mg.kg-1)组与中剂量(150 mg.kg-1)组小鼠脊髓与脑NO2-与NOS含量和模型组比较显著降低(P<0.01;P<0.05)。AMG+L-Arg组和AMG组比较小鼠15min内扭体次数显著增多(P<0.05);而AMG+L-NAME组和AMG组比较小鼠15min内扭体次数显著下降(P<0.05)。L-Arg,L-NAME对AMG在AA扭体致痛小鼠镇痛,AMG(150 mg.kg-1)组小鼠脊髓与脑NO2-含量和模型组比较显著降低(P<0.05)。AMG和L-NAME可减少FA致痛小鼠第二时相累计舔足时间。结论L-Arg和L-NAME可能对AMG镇痛作用有一定影响,AMG可能通过抑制脊髓与脑NO生成发挥镇痛作用。

Objective： To investigate the antinociception mechanism of amtolmetin guacyl（AMG） mediated by nitric oxide（NO）. Methods： The writhing test of mice was performed to determine the analgesic effect of AMG. and the NO2^- , nitric oxide synthase （NOS） content in the brain, spinal cord and blood were examined respectively. While L-Arg （a traditional NO donor） and L-NAME （an inhibitor of NOS） were co-administrated with AMG in the formalin test of mice and the writhing test of mice. Simultaneously the NO2^- concentration in the brain, spinal cord and blood of different groups was determined in the writhing test. Results ： In the first writhing test of mice using AMG, compared with the CMC group, AMG at 300, 150 mg ·kg^-1 significantly decreased the NO2^- and NOS concentration in the spinal cord and the brain. In the second writhing test of mice using AMG co-administered with L-Arg or L-NAME, the number writhing of AMG ＋ L-Arg group was significantly increased but the number writhing of AMG ＋ L- NAME group was remarkably reduced compared with those in AMG group. The NO2^- level in spinal cord of pretreatment with AMG 150 mg ·kg^-1 was highly lowered compared with that in the CMC group. The total licking time of the second phase of formalin test of mice was alleviated in the groups administered AMG ＋ L-NAME. Conclusion： L-Arg and L-NAME may affect the antinociception of AMG, in the writhing test, and the analgesic effect of AMG may be relative to its inhibition of the nitric oxide synthesis in the spinal cord and brain.