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依托咪酯对新生大鼠离体脊髓运动神经元下行激活的影响

郑超, 汪萌芽^*

皖南医学院细胞电生理研究室，芜湖 241002

摘要

脊髓下行激活通路是启动和调控随意运动的重要途径，全麻药对其的影响是否参与了肌松作用的产生及其兴奋性氨基酸受体机制，尚不完全清楚。为深入探索依托咪酯(etomidate, ET)对离体大鼠脊髓运动神经元(motoneuron, MN)下行激活的影响及可能的谷氨酸受体机制，本实验应用7~14日龄新生大鼠脊髓切片MN细胞内记录技术，观察ET对MN电刺激脊髓同侧腹外侧索(ventrolateral funiculus, VLF)诱发兴奋性突触后电位(excitatory postsynaptic potential, EPSP)(简称VLF-EPSP)的作用。对能稳定记录到VLF-EPSP的MN依次灌流0.3、3.0 (相当于临床浓度)和30.0 µmol/L的ET。结果显示0.3 µmol/L的ET对VLF-EPSP及其N-甲基-D-门冬氨酸(N-methyl-D-aspartate, NMDA)和非NMDA (non-NMDA)受体成分具有双向作用：既可表现增强，使VLF-EPSP和NMDA受体介导的VLF-EPSP成分的时程延长、曲线下面积增大和(或)半幅时程延长(P < 0.05)，non-NMDA受体介导的VLF-EPSP成分幅度升高、曲线下面积增大、半幅时程延长(P < 0.05)；也可表现抑制，使VLF-EPSP及其NMDA和non-NMDA受体成分的幅度降低、曲线下面积减小(皆P < 0.05)。而灌流浓度≥3.0 µmol/L的ET，仅呈浓度、时间依赖性抑制，表现为VLF-EPSP及其NMDA和non-NMDA受体成分的幅度和(或)时程和(或)曲线下面积显著降低(P < 0.05或P < 0.01)。此外，与VLF-EPSP的non-NMDA受体成分相比，≥3.0 µmol/L的ET更易于压抑NMDA受体成分。以上结果表明，ET对下行激活的突触传递及介导VLF-EPSP的谷氨酸受体呈现浓度相关的差异性作用。

关键词： 依托咪酯; 脊髓; 运动神经元; 下行激活; 兴奋性突触后电位; 谷氨酸受体

分类号：R338

[Effects of etomidate on descending activation of motoneurons in neonatal rat spinal cord in vitro.] [Article in Chinese]

ZHENG Chao, WANG Meng-Ya^*

Cell Electrophysiology Laboratory, Wannan Medical College, Wuhu 241002, China

Abstract

Descending activation pathways in spinal cord are essential for inducing and modulating autokinesis, but whether the effects of general anesthetic agents on the descending pathways are involved in initiation of skeletal muscle relaxation or not, as well as the underlying mechanisms on excitatory amino acid receptors still remain unclear. In order to explore the mechanisms underlying etomidate’s effects on descending activation of spinal cord motoneurons (MNs), the conventional intracellular recording techniques in MNs of spinal cord slices isolated from neonatal rats (7–14 days old) were performed to observe and analyze the actions of etomidate on excitatory postsynaptic potential (EPSP) elicited by electrical stimulation of the ipsilateral ventrolateral funiculus (VLF), which was named VLF-EPSP. Etomidate at 0.3, 3.0 (correspond to clinical concentration) and 30.0 µmol/L were in turn perfused to MN with steadily recorded VLF-EPSPs. At low concentration (0.3 µmol/L), etomidate increased duration, area under curve and/or half-width of VLF-EPSP and N-methyl-D-aspartate (NMDA) receptor-mediated VLF-EPSP component (all P < 0.05), as well as amplitude, area under curve and half-width of non-NMDA receptor-mediated VLF-EPSP component (all P < 0.05), or decreased amplitude and area under curve of VLF-EPSP, its NMDA receptor component, and non-NMDA receptor component (all P < 0.05). However, at 3.0 and 30.0 µmol/L, it was only observed that etomidate exerted inhibitory effects on amplitude and/or duration and/or area under curve of VLF-EPSP (P < 0.05 or P < 0.01) with concentration- and time-dependent properties. Moreover, NMDA receptor-mediated VLF-EPSP component was more sensitive to etomidate at ≥ 3.0 µmol/L than non-NMDA receptor-mediated VLF-EPSP component did. As a conclusion, etomidate, at different concentrations, exerts differential effects on VLF-EPSP and glutamate receptors mediating the synaptic transmission of descending activation of MNs in neonatal rat spinal cord in vitro.

Key words: Etomidate; spinal cord; motor neurons; descending activation; excitatory postsynaptic potential; glutamate receptors

收稿日期：2011-11-25　　录用日期：2012-02-16

通讯作者：汪萌芽　　E-mail: wangmy@wnmc.edu.cn

引用本文：

郑超, 汪萌芽. 依托咪酯对新生大鼠离体脊髓运动神经元下行激活的影响[J]. 生理学报 2012; 64 (2): 155-162.

ZHENG Chao, WANG Meng-Ya. [Effects of etomidate on descending activation of motoneurons in neonatal rat spinal cord in vitro.] [Article in Chinese]. Acta Physiol Sin 2012; 64 (2): 155-162 (in Chinese with English abstract).