【摘要目的】：NMDA受体是中枢神经系统最主要的兴奋性递质门控离子通道受体，但对于NMDA受体是否是静脉麻醉药丙泊酚全麻作用的分子靶位，目前尚存在较大的争议和分歧。为此我们采用整体清醒制动大鼠模型，选择海马CA1区伤害兴奋性神经元（NENs）作为研究对象，在体观察了丙泊酚对NENs自发放电的影响作用，旨在确定NMDA受体在其中的可能介导作用。方法：建立整体清醒制动大鼠模型，鉴定并选择海马CA1区伤害兴奋性神经元（NENs）、即给于外周伤害性刺激（有齿镊钳夹大鼠同侧后肢皮肤）后放电迅速增加的神经元进行细胞外电生理记录。药物丙泊酚和NMDA受体拮抗剂（MK801）分别采用静脉全身给药或行内侧隔核局部微注射给药，观察给药前后NENs自发放电的变化情况。结果：共记录到24个海马CA1区伤害兴奋性神经元（NENs），基础放电频率平均为31.98.9spikes/s。其中11个NENs（基础放电频率平均为31.210.5spikes/s），静脉全身给于丙泊酚（2.0mg/kg）后NENs的自发放电明显受抑（4.32.6spikes/s），平均降幅86.2%。而静脉预注射MK801（0.5mg/kg）可显著降低丙泊酚的抑制作用（神经元的自发放电由阻断前的26.45.6 spikes/s下降为12.84.2 spikes/s），平均降幅47.7%（与未用MK801相比，P<0.01）。对于13个记录到的NENs（基础放电频率平均为29.19.5spikes/s），内侧隔核微注射丙泊酚(60ng，Ms)也明显抑制NENs自发放电(10.75.6spikes/s)，平均降幅63.2%。而预先微注射MK801(8ng，Ms)则明显减轻丙泊酚的抑制作用（神经元的自发放电由阻断前的40.712.9spikes/s下降为32.310.7spikes/s），平均降幅20.9%（与未用MK801相比，P<0.01）。结论：丙泊酚明显抑制海马CA1区伤害兴奋性神经元的自发放电，其部分作用是由NMDA受体所介导。
关键词：丙泊酚；NMDA受体；海马神经元；细胞外记录

NMDA receptor involved in the modulation of Propofol on nociceptive excitatory neurons in rat hippocampal field CA1

Yun-Fei Cao, Wei-Zhong Wang, Wei-Feng Yu

Abstract: Object: NMDA receptor is the best characterized excitatory neurotransmitter-gated receptor in mammalian brain, however whether NMDA receptor is one of putative targets involved in general anesthesia of propofol is still under controversial. He免费论文网 【http://www.51lunwen.net】re we established the model of extrcellular recording of a single neuron in the hippocampal CA1 area in intact awake rat, and examined the inhibition of propofol on the spontaneous activities of nociceptive excitatory neurons(NENs) and the possible roles of NMDA receptor involved.
Methods: Spontaneous activities of the dorsal hippocampal field CA1 neurons were extracellularly recorded by single-barreled electrode in intact awake rat, which was paralyzed with pancuronium and whose respiration controlled via a nonrebreathing system. Nociceptive excitatory neurons(NENs) were identified electrophysiologically due to a quick increase in their discharge frequencies induced by mechanical noxious stimulation, and the effects of propofol administrated via intravenous injection(IV) or microinjection into medial sepato nucleai (Ms) on NENs, were observed with or without the pretreatment of MK-801(NMDA receptor antagonist).
Results: Of total 24 NENs recorded, the averaged maintained firing rate of these neurons was 31.98.9 spikes/s.In 11 NENs(baseline spontaneous discharges 31.210.5spikes/s) , Intravenous injection of propofol(2.0mg/kg) markedly suppressed the neural activity of NENs(4.32.6 spikes/s),with an average reduction of 86.2%. While pretreated with MK801(0.5mg/kg, IV) ,The propofol-induced suppressive effects were obviously attenuated(26.45.6spikes/s to 12.84.2spikes/s) ,with an average reduction of 47.7%(as compared to that withou 本文来自：免费论文网 [http://www.51lunwen.net]