异氟烷于脊髓NMDA受体甘氨酸位点的镇痛作用及与NOS／NO的关系

Mechanism of isofluranes analgesia on the glycine site of NMDA receptor and its relation with NOS/NO

目的分析异氟烷于脊髓NMDA受体甘氨酸位点的镇痛作用及该作用与NOS／NO的关系。方法在甩尾法实验中，观察鞘内注射NMDA受体甘氨酸位点的激动剂D-丝氨酸对异氟烷镇痛作用的影响及腹腔预注射NOS抑制剂L．NAME后的变化。用分光光度法进一步观察异氟烷及给工具药对小鼠脊髓NOS活性及NO产量的影响。结果鞘内D．Ser（0．025ng、0．05ng、0．1ng）可拮抗甩尾实验中异氟烷镇痛作用（P〈0．05，P〈0．01），而腹腔预注射NOS抑制剂L．NAME（0．5mg／kg，1mg／kg）后，鞘内D-Ser的拮抗作用减弱或消失（P〈0．05，P〈0．01）。异氟烷抑制小鼠脊髓NOS活性、减少NO产量（P〈0．05），鞘内D-丝氨酸（1ng）可拮抗异氟烷对异氟烷小鼠脊髓NOS活性、NO产量的影响（P〈0．01），而预注射L—NAME取消鞘内D-丝氨酸的拮抗作用。结论脊髓NMDA受体甘氨酸位点介导异氟烷的镇痛作用，而该作用可能与脊髓NOS／NO有关。

Objective To investigate whether the glycine site of NMDA receptor mediates the analgesia effect of isoflurane and the mechanism of isoflurane＇s analgesia on the glycine site of NMDA receptor. Methods The injection analgesia model of isoflurane in tail immersion test was constructed. Tail flick latency were observed after D-Serine （ agonist of glycine siteB） were administrated. After intraperitoneal pretreatment with L-NNME （1.0 mg/kg, 0.5 mg/kg ）, the effect of intrathecal D-serine was observed in tail immersiontest. The change of activiry of NOS and production of NO in the miceg spinal cord were observed by spectrophotometry in mice. Results Intrathecal administration of D-serine （0.025 rig, 0.05 ng, 0.1 ng） antagonized analgesia induced by isoflurane in tail -im- mersion test （P 〈 0.01,P 〈 0.05 ） and pretreatment of L-NAME （0.5 mg/kg, 1 mg/kg） decreased or concealed the effect of D-serine （P 〈 0.05, P 〈 0.01 ）. Isoflurane supressed the activity of NOS and production of NO in the spinal cord. D-serine （1 ng）antagnized the effect of isoflurane. Pretreatment of L-NAME concealed the antagnism of D-Serine. Conclusion Glycine site of NMDA receptor in the spinal cord mediates the analgesia of isoflurane in mice and NOS/NO involved the mechanism.