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

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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30.0μmol/L的ET。结果显示0.3μmol/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≥3.0μmol/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,≥3.0μmol/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。 Spinal cord activation pathway is an important way to start and regulate voluntary exercise. Whether anesthesia is involved in the production of muscle relaxants and its excitatory amino acid receptor mechanism is not fully understood. In order to further explore the effect of etomidate (ET) on the down-regulation of motoneuron (MN) in isolated rat spinal cord and the possible mechanism of glutamate receptor, this experiment used 7-14 day old neonatal rats The effect of ET on excitatory postsynaptic potential (EPSP) (VLF-EPSP) induced by MN in the spinal cord of ipsilateral ventrothorax funiculus (VLF) was observed. MNs capable of stably recording VLF-EPSP were sequentially perfused with 0.3, 3.0 (equivalent to clinical concentration) and 30.0 μmol / L of ET. The results showed that 0.3μmol / L ET had a bidirectional effect on VLF-EPSP and its N-methyl-D-aspartate (NMDA) and non-NMDA receptor components : The expression of VLF-EPSP and NMDA receptor-mediated prolongation of VLF-EPSP components, the area under the curve and / or prolongation of half-time duration (P <0.05) The amplitude of VLF-EPSP components increased, the area under the curve increased, the half-length time course prolonged (P <0.05), and the amplitude of VLF-EPSP and its NMDA and non-NMDA receptor components also decreased. Under the area decreased (all P <0.05). However, the ET concentration of 3.0μmol / L was only inhibited in a concentration-dependent and time-dependent manner, showing the amplitude and duration of VLF-EPSP and its NMDA and non-NMDA receptor components and the area under the curve Significantly decreased (P <0.05 or P <0.01). In addition, ≧ 3.0 μmol / L of ET is more likely to suppress NMDA receptor components than non-NMDA receptor components of VLF-EPSP. The above results indicate that ET has a differential effect on the synaptic transmission of down-activation and the concentration-dependent glutamate receptor that mediates VLF-EPSP.
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