侧脑室或鞘内注射NCS-382对七氟烷催眠及镇痛作用的影响

Effect of intracerebroventricular or intrathecal injection of NCS-382 on hypnosis and analgesia action of sevoflurane

目的探讨γ-羟基丁酸(GHB)受体与七氟烷(sevoflurane)催眠及镇痛作用的关系。方法①催醒实验小鼠ip七氟烷5.5 ml.kg-1催眠后i,cv给予NCS-382 0.050,.25和1.25 mg.kg-1,检测翻正反射消失时间。②镇痛实验小鼠分为ip七氟烷2.0 ml.kg-1镇痛和生理盐水2大组,每组再分为ith人工脑脊液(aCSF),NCS-382 0.050,.25和1.25 mg.kg-1亚组,热板检测热板疼痛指数(HPPT)。③扭体实验小鼠分为sc七氟烷5.5 ml.kg-1镇痛和生理盐水2大组,再分为ith给予aCSF,NCS-382 0.050,.25和1.25 mg.kg-1亚组,检测扭体次数。结果与七氟烷模型组相比,小鼠七氟烷催眠后i,cv给予NCS-382 0.05,0.25和1.25mg.kg-1,可明显缩短翻正反射消失时间,分别提前50,52和78 min(P<0.01)。热板法中i,th给予NCS-382对清醒小鼠HPPT无明显影响,但能使麻醉小鼠的HPPT分别降低4.4,5.7和4.4 s(P<0.01)。扭体实验中,与正常对照组相比s,c给予七氟烷可使小鼠的扭体次数减少14次(P<0.01),但ith给予NCS-382对清醒及麻醉小鼠扭体次数无明显影响。结论 GHB可能是七氟烷催眠作用和抗热刺激伤害的靶位之一,但与其抗化学刺激和炎症刺激作用可能无关。

OBJECTIVE To investigate the relationship between gamma-hydroxybutyric acid（GHB） receptors and hypnotic and analgesic effects of sevoflurane.METHODS ① Hypnosis experiment： after mice were ip given sevoflurane 5.5 ml·kg^-1 to get hypnotized,NCS-382 0.05,0.25 and 1.25 mg·kg^-1 were given intracerebroventricularly（icv） and sleeping time（ST） was observed.② Analgesia experiment： mice in normal saline and sevoflurane 2.0 ml·kg^-1 groups were ith given artificial cerebral spinal fluid（aCSF）,and NCS-382 0.05,0.25 and 1.25 mg·kg^-1 as subgrouping,respectively.The pain threshold in hot-plate pain test（HPPT） was observed.③ Writhing test： mice in normal saline and sevoflurane 5.5 ml·kg^-1（sc） groups were given aCSF,and NCS-382 0.05,0.25 and 1.25 mg·kg^-1（ith） as subgrouping,respectively.The writhing times were observed.RESULTS After mice were hypnotized by sevoflurane,icv NCS-382 0.05,0.25 and 1.25 mg·kg^-1could significantly shorten ST in mice treated with sevoflurane compared with aCSF by 50,52 and 78 min（P0.01）.In hot-plate test,NCS-382 did not affect HPPT in conscious mice（P0.05）,but could significantly decrease HPPT in mice treated with sevoflurane by 4.4,5.7 and 4.4 s（P0.01） respectively.Sevoflurane（sc） could significantly lead to a 14-fold decrease of writhing times（P0.01）,but NCS-382 couldn′t（P0.05）.CONCLUSIONGHB may be one of the important targets for hypnotic effects and analgesic effects on thermal-induced nociception,but have no correlation with chemical-induced or inflammation-induced nociception of sevoflurane.