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目的探讨γ-羟基丁酸受体拮抗剂NCS-382对丙泊酚、氯胺酮和依托咪酯催眠及镇痛作用的影响。方法①催醒实验:120只小鼠分别ip给予丙泊酚200 mg.kg-1、氯胺酮150 mg.kg-1和依托咪酯40mg.kg-1制备催眠模型后,再按分组分别icv给予人工脑脊液(aCSF),NCS-382 1,5和25μg.kg-1,记录睡眠时间。②热板实验:80只小鼠分别ip给予生理盐水10 ml.kg-1和氯胺酮40 mg.kg-1后,再按分组分别ith给予aCSF和NCS-382 1,5和25μg.kg-1,记录热板法痛阈。③扭体实验:80只小鼠分别ip给予生理盐水10 ml.kg-1和氯胺酮40 mg.kg-1后,再按分组分别ith给予aCSF和NCS-382 1,5和25μg.kg-1,1 min后ip给予1.0%冰醋酸溶液10 ml.kg-1,记录15 min内小鼠扭体次数。结果①催醒实验:NS-382 1,5和25μg.kg-1组小鼠的睡眠时间明显缩短,从丙泊酚组的(81±30)min缩短到44±23,40±21,(40±17)min;从氯胺酮组的(19±4)min缩短到8±4,12±3,(15±4)min;从依托咪酯组的(31±11)min缩短到21±9,22±6,(23±10)min;②热板实验:小鼠在给予氯胺酮麻醉后10～30 min痛阈明显长于基础痛阈(P<0.05),NCS-382对氯胺酮所致痛阈延长无改善作用。单用NCS-382对正常小鼠的痛阈无影响;③扭体实验:单用NCS-382对正常小鼠的扭体次数无明显差异;氯胺酮组小鼠扭体次数明显少于正常对照组(P<0.05),给予NCS-382对此无改善作用。结论γ-羟基丁酸受体可能介导了静脉麻醉药丙泊酚、氯胺酮和依托咪酯的催眠作用,但可能与氯胺酮镇痛作用关系不大。
Objective To investigate the effects of γ-hydroxybutyrate receptor antagonist NCS-382 on hypnotic and analgesic effects of propofol, ketamine and etomidate. Methods ① Awake experiment: 120 mice were ip given propofol 200 mg.kg-1, ketamine 150 mg.kg-1 and etomidate 40mg.kg-1 preparation hypnosis model, and then by group were given icv Artificial cerebrospinal fluid (aCSF), NCS-382 1,5 and 25 μg.kg-1, were recorded for sleep time. ② hot plate experiment: 80 mice were given ip saline 10 ml.kg-1 and ketamine 40 mg.kg-1, respectively, according to the group were given ith aCSF and NCS-382 1,5 and 25μg.kg-1 , Record the hot plate method pain threshold. ③ writhing experiments: 80 mice were given saline ip 10 ml.kg-1 and ketamine 40 mg.kg-1, respectively, according to the group were given ith aCSF and NCS-382 1,5 and 25μg.kg-1 , After 1 min ip given 1.0% glacial acetic acid solution 10 ml.kg-1, record the number of writhing in mice within 15 min. Results (1) Awakening test: The sleep time of NS-382 1,5 and 25 μg.kg-1 groups was significantly shortened from (81 ± 30) min in propofol group to 44 ± 23,40 ± 21, ( 40 ± 17) min, shortened from (19 ± 4) min in ketamine group to 8 ± 4,12 ± 3 and (15 ± 4) min, shortened from 31 ± 11 min in etomidate group to 21 ± 9 , 22 ± 6, (23 ± 10) min, respectively. ② Hot plate test: The pain threshold of mice in 10-30 min after ketamine anesthesia was significantly longer than that of basal pain threshold (P <0.05). NCS- Prolonged no improvement. 383 had no effect on the pain threshold of normal mice alone. (3) The writhing test showed that there was no significant difference in the number of writhing in NCS-382 mice. The number of writhing in ketamine group was significantly less than that of the normal control group (P <0.05), giving NCS-382 did not improve this effect. Conclusion γ-hydroxybutyric acid receptor may mediate hypnotic effects of propofol, ketamine and etomidate, but may not be related to the analgesic effects of ketamine.