异氟烷催眠、镇痛作用与NMDA受体甘氨酸位点的关系

目的分析异氟烷催眠、镇痛作用与NMDA受体甘氨酸位点的关系。方法建立小鼠异氟烷注射催眠、镇痛模型后,在小鼠催醒、甩尾、福尔马林实验中,观察侧脑室或鞘内注射NMDA受体甘氨酸位点的激动剂D-丝氨酸(D-Serine,D-Ser)后小鼠睡眠时间、甩尾潜伏期或累计舔足时间的变化;用免疫组化方法观察异氟烷及鞘内用药对福尔马林小鼠脊髓Fos蛋白表达的影响。结果侧脑室注射D-Ser对异氟烷的催眠时间无影响(P>0.05)。鞘内注射D-Ser(0.025、0.05、0.1ng)可拮抗甩尾实验、福尔马林实验Ⅰ相中异氟烷的镇痛作用(P<0.05,P<0.01),而对福尔马林实验Ⅱ相异氟烷的镇痛作用无影响(P>0.05)。鞘内注射D-Ser0.05ng可拮抗异氟烷对福尔马林小鼠脊髓Fos蛋白表达的抑制作用(P<0.01)。结论异氟烷催眠作用与脑内NMDA受体甘氨酸位点关系不大;脊髓NMDA受体甘氨酸位点介导异氟烷对热、化学刺激的镇痛作用,而与异氟烷对慢性炎性疼痛的镇痛作用无明显关系。

Relationship between analgesia and hypnosis of isoflurane and glycine site of NMDA receptor

Aim To investigate the relationship between analgesia and hypnosis of the inhaled anesthetic isoflurane and glycine site of NMDA receptor(glycine siteB). Methods Construct the injection analgesia and hypnosis model of isoflurane. In analeptic test, tail-immersion test and formalin test, the change of the sleeping time, tail-immersion latency and the accumulative licking injected jaw time were observed after D-serine(agonist of glycine siteB) were administrated. The effect of intrathecal D-serine on isoflurane′s suppression of Fos expression in the spinal cord in mice receiving noxious pain stimulation was observed by immunochemistry method. Results D-serine (2.5~10 μg icv) had no effect on the sleeping time induced by isflurane (P>0.05). Intrathecal administration of D-serine (0.025, 0.05, 0.1 ng), antagonized analgesia induced by isoflurane in tail-immersiontest and the early phase of formalin test (P<0.01,P<0.05) and had no effect on the late phase in formalin test(P>0.05). Intrathecal administration of D-serine (0.05 ng) antagonized and the isoflurane′s suppression to the expression of Fos-protein in the spinal cord in mice(P<0.05, P<0.01). Conclusion Glycine siteB in the brain had no relationship with the hypnogenesis induced by isoflurane. Glycine siteB in the spinal cord contributed to the antinociceptive effect of acute pain of systemic isoflurane in mice.