氯胺酮镇痛作用与3种受体的关系  

Relationship of the analgesic effect of ketamine with NMDA receptor,opioid receptor and glycine receptor

作　　者：李惠萍[1] 吴钢[1] 韦成全[1] 莫玉兰[1] 裴世成[1] 戴体俊[2] 

机构地区：[1]柳州医学高等专科学校药理教研室,广西柳州545006 [2]徐州医学院麻醉药理学教研室

出　　处：《解放军医学杂志》2007年第10期1048-1050,1074,共4页Medical Journal of Chinese People's Liberation Army

基　　金：广西医药卫生计划课题项目(Z2005199)

摘　　要：目的探讨氯胺酮镇痛作用与N-甲基-D-天冬氨酸(NMDA)受体、阿片受体、甘氨酸受体的关系,阐明氯胺酮的镇痛作用靶点。方法将480只小鼠随机分成3大组(NMDA组、纳络酮组和士的宁组),分别进行扭体法和热板法实验,每组160只小鼠随机分为空白组和氯胺酮组,每组再分为8小组(n=10)。NMDA组:空白组鞘内注射人工脑脊液(aCSF)或2.5、5、10ng NMDA(NMDA用aCSF稀释),均10μl,注射时间为10s;氯胺酮组均腹腔注射氯胺酮20mg/kg,5min后分别鞘内注射acsF10μl或2.5、5、10ng NMDA。纳络酮组和士的宁组:动物分组与用药(纳络酮或士的宁)方法同NMDA组。通过扭体法实验分别观察鞘内注射NMDA、腹腔注射纳络酮和士的宁对腹腔注射0.6%冰醋酸溶液(10ml/kg)的小鼠15min内扭体次数的影响。通过热板法观察小鼠用药前、用药后5、10、15、20、30min的热板法痛阈(HPPT)。结果NMDA对空白组小鼠HPPT及扭体次数均无明显影响(P>0.05),但可增加氯胺酮组小鼠的扭体次数(P<0.05),缩短其HPPT(P<0.01)。腹腔注射纳络酮(1、2、4mg/kg)或士的宁(0.25、0.5、0.75μg)对空白组小鼠HPPT、扭体次数和氯胺酮组小鼠的扭体次数均无明显影响(P>0.05),但可缩短氯胺酮组小鼠的HPPT(P<0.05,P<0.01)。结论氯胺酮对热刺激的镇痛作用与NMDA受体、阿片受体、甘氨酸受体有关,对化学刺激的镇痛作用与NMDA受体有关,而与阿片受体、甘氨酸受体关系不大。Objective To explore the relationship of analgesic effect of ketamine with three receptors （NMDA receptor, opioid receptor and glycine receptor）, and to look for the target for analgesic effect of ketamine. Methods 480 mice were randomly divided into 3 groups （NMDA group, naloxone group and strychnine group） for performing hot plate and writhing tests. The 160 mice in each group were randomly assigned to comprise 2 medium subgroups （control subgroup and ketamine subgroup）, moreover, one medium subgroup included 4 small groups with 10 mice each. In NMDA group, mice in control subgroup were intratheeally injected with 10μl of artificial cerebrospinal fluid （aCSF） or 2. 5ng, 5ng or 10ng of NMDA （NMDA was diluted with aCSF） in ten seconds. The animals in naloxone group and strychnine group were divided to subgroups in same manner as the NMDA group. Writhing tests were used to observe the effects caused by NMDA intrathecal injection, and naloxone and strychnine intraperitoneal injection in the mice which had been intraperitoneally injected with glacial acetic acid （0. 1ml/10g） within 15 minutes, respectively. Hot-plates were used to observe the pain threshold in hot- plate tests （HPPT） of before and within 5, 10, 15, 20, 30 minutes after injection. Results NMDA had no obvious effect on the HPPT and writhing times of the mice in comparison groups （P〉0. 05）, but it increased writhing times of mice （P〈0. 05） and decreased their HPPT （P〈0. 01） after ketamine injection. Intraperitoneal injection of naloxone （1, 2 and 4mg/kg） or strychnine （0. 25, 0. 5 and 0. 75μg） had no obvious effect on the HPPT and writhing times of the mice, and no effect on writhing times of the mice after injection of ketamine （P〉0. 05）, but HPPT was decreased（ P〈0.05, P〈0. 01）. Conclusion Analgesic effect of ketamine on heat stimulation is related to NMDA receptor, opioid receptor and glycine receptor. Analgesic effect of ketamine on chemical stimulation is related to NMDA recepto

关 键 词：氯胺酮 镇痛 NMDA 纳络酮 士的宁 NMDA受体 受体 阿片样 受体 甘氨酸 

分 类 号：R614[医药卫生—麻醉学]