N-甲基-D-天门冬氨酸受体与吸入麻醉药对小鼠催眠、镇痛作用的关系

Relationship between NMDA receptors and the hypnotic and analgesic effects of inhalation anesthetics in mice

目的探讨N．甲基．D．天门冬氨酸(NMDA)受体与安氟醚、异氟醚、七氟醚对小鼠催眠及镇痛作用的关系。方法实验动物选用昆明种小鼠,雌雄不拘。第一部分为催眠实验,120只小鼠随机分成安氟醚、异氟醚、七氟醚三组,分别腹腔注射安氟醚2 ITIl·kg～、异氟醚1．2IrIl·kg～、七氟醚5 rnl·奴～,每组又分成人工脑脊液(aCSF‘)、NMDA 25、NMDA 50及NMDA 75亚组,每亚组10只,各组翻正反射消失后立即侧脑室注射aCSF、NDMA25、50、75 mg 10 m,记录翻正反射恢复(RT)时间。第二部分为镇痛实验,160只小鼠随机分成对照、安氟醚、异氟醚、七氟醚组,对照组不给予任何处理,安氟醚、异氟醚、七氟醚组分别皮下注射安氟醚1．5 llll·kg一、异氟醚0．8 Jnl·kg一、七氟醚4．5 llll·kg～,各组又分成 aCSF、NMDA 2．5、NMDA5及NMDA 10亚组,每亚组10只,各组注药后10 min鞘内注射aCSF或2．5、5、 10 ng NMDA lO出,1 min后腹腔注射O．6％冰醋酸,记录扭体次数。结果催眠实验中,安氟醚、异氟醚、七氟醚组的亚组间比较RT差异无统计学意义(P>0．05)。镇痛实验中,与aCSF亚组比较,对照组的NMDA 2．5亚组、NMDA 5亚组、NMDA 10亚组扭体次数差异无统计学意义,安氟醚、异氟醚、七氟醚组的NMDA 5 ng亚组、NMDA 10 ng亚组扭体次数增加(P<O．05或0．01)。与对照组比较,安氟醚、异氟醚、七氟醚组的各亚组扭体次数均减少(P<0．01)。结论脑内的NMDA受体与安氟醚、异氟醚、七氟醚对小鼠的催眠作用无关,脊髓的NMDA受体与安氟醚、异氟醚、七氟醚对小鼠的镇痛作用有关。

Objective To investigate the relationship between N-methyl-D aspartate （NMDA） receptors and the hypnotic and analgesic effects of enflurane, isoflurane and sevoflurane. Melhods Kunming mice weighing 18-22 g were used in this study. The experiment was carried out in 2 parts. In Part Ⅰ 120 mice were randomly divided into 3 groups （ n = 40 each） ; each group received intraperitoneal （IP） enflurane 2 ml·kg^-1 or isoflurane 1.2ml·kg^-1 or sevotlurane 5 ml·kg^-1 Each group was further divided randomly into 4 subgroups （ n = 10 each） and each subgroup received artificial cerebro-spinal fluid （aCSF） 10/11 or NMDA 25, 50 or 75 ng in 10/11 aCSF injected into the lateral ventricle of the brain as soon as the animals lost righting reflex. The time for the recovery of righting reflex was recorded. In Part Ⅱ 160 mice were randomly divided into 4 groups （n = 40 each）： （1） control group received no inhalation anesthetic; （2） enflurane group received enflurane 1.5 ml·kg^-1 subcutaneously s.c. ; （3） isoflurane group isoflurane 0.8 ml·kg^-1 s.c. and （4） sevoflurane group sevoflurane 4.5 ml·kg^-1 s.c.. Each group was further divided randomly into 4 subgroups （ n = 10 each）. Each subgroup received intrathecal （IT） aCSF 10 /11 or NMDA 2.5 ng or 5.0 ng or 10 ng in aCSF 10/11 at 10 min after subcutaneous injection of inhalation anesthetic. 6% acetic acid 0.1 ml·10 g^-1 was injected IP at 1 rain after intrathecal administration. The number of writhing induced by acetic acid was recorded. Results In Part Ⅰ of the experiment there was no significant difference in the duration of anesthesia induced by the 3 inhalation anesthetics between the 4 subgroups. In Part Ⅱ subcutaneous injection of the 3 inhalation anesthetics significantly reduced the number of writhing induced by IP acetic acid. In control group which received no inhalation anesthetic there was no significant difference in the number of writhing between the 4 subgroups. In the 3 inhalation anesthetic groups NMDA 5.0 and 10 ng IT significantly increased the number of writhing induced by IP acetic acid in a dose dependent manner as compared with aCSF subgroup. Conclusion Cerebral NMDA receptors do not play an important role in the hypnotic effect of evflurane, isoflurane and sevoflurane while spinal NMDA receptors are involved in the analgesic effect of the 3 inhalation anesthetics.