NCS-382对丙泊酚、氯胺酮和依托咪酯催眠镇痛作用的影响  

Effects of NCS-382 on hypnosis and analgesia of propofol,ketamine and etomidate in mice

作　　者：宋苏沛[1] 王雷[1] 廖艺聪[1] 刘晶晶[1] 张明阳 周美艳[2] 周慧轩[1] 唐然[1] 戴体俊[3] 

机构地区：[1]徐州医学院麻醉学院,江苏徐州221002 [2]徐州医学院研究生学院,江苏徐州221002 [3]徐州医学院江苏省麻醉学重点实验室,江苏徐州221002

出　　处：《中国药理学与毒理学杂志》2011年第4期344-348,共5页Chinese Journal of Pharmacology and Toxicology

基　　金：国家自然科学基金资助项目(30471657);国家自然科学基金资助项(30872432);国家自然科学基金资助项目(39970715);江苏省自然科学基金资助项目(BK2001143)~~

摘　　要：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 effect of NCS-382 on hypnosis and analgesia of propofol,ketamine and etomidate in mice.METHODS ① Analeptic test： a total of 120 mice were ip given propofol 200 mg·kg-1,ketamine 150 mg·kg-1 and etomidate 40 mg·kg-1 to establish a hypnosis model,respectively.Then,the mice were icv given aCSF and NCS-382 1,5 and 25 μg·kg-1,respectively,and sleeping time was recorded.② Hot-plate test： a total of 80 mice were ip given normal saline 10 ml·kg-1 and ketamine 40 mg·kg-1,respectively,and were ith given aCSF and NCS-382 1,5 and 25 μg·kg-1,respectively.The pain threshold in hot-plate test（HPPT） was recorded.③ Writhing test： a total of 80 mice were respectively ip given normal saline 10 ml·kg-1 and ketamine 40 mg·kg-1.Then,the mice were ith given aCSF and NCS-382 1,5 and 25 μg·kg-1,respectively.They were ip given 1.0% acetic acid 10 ml·kg-1,then writhing time within 15 min were recorded.RESULTS ① Analeptic test： the sleeping time in NCS-382 1.5 and 25 μg·kg-1 groups was significantly shortened by propofol for（81±30）min to 44±23,40±21 and（40±17）min,by ketamine for（19±4）min to 8±4,12±3 and（15±4）min;by etomidate for（31±11）min to 21±9,22±6 and（23±10）min.② Hot-plate test： compared with self basal HPPT,ketamine could significantly prolong HPPT 10-30 min after administration（P0.05）.NCS-382 had no effect on the prolonged HPPT by ketamine.③ Writhing test： compared with normal control group,NCS-382 had no effect on writhing times.The writhing times in ketamine groups decreased significantly.NCS-382 had no effect on the increased writhing times induced by ketamine.CONCLUSION NCS-382 may mediate the hypnotic effect of propofol,ketamine and etomidate,but it may have little analgesic effect as ketamine does.

关 键 词：受体 Γ-羟基丁酸 NCS-382 丙泊酚 氯胺酮 依托咪酯 催眠 镇痛 

分 类 号：R96[医药卫生—药理学]