目的了解全麻药依托咪酯(ET)对新生大鼠离体脊髓运动神经元(MN)感觉传人的作用及受体机制。方法应用新生大鼠(7~14d)脊髓切片MN细胞内记录技术,观察ET对MN细胞电生理特性和电刺激脊髓同侧背根残端(DR)诱发兴奋性突触后电位(DR—EPSP)的作用,并进行受体机制的分析。结果ET对MN的动作电位(AP)和放电频率呈浓度依赖性抑制。与正常MN比较,0.3、3.0和30.0μmol/L的ET(3.0μmol/L相当于临床浓度0.8~20.0μmol/L)可分别压抑AP的幅度(mV:57.5±33.5、33.8±34.9、31.2±34.9比74.3±9.4,P〈0.05或P〈0.01);0.3btmol/L的ET对DR—EPSP及介导EPSP的谷氨酸受体[包括N-甲基-D-门冬氨酸(NMDA)和非NMDA受体]具有双向作用,既可表现为增强[DR—EPSP的曲线下面积(AUC)为67.1±43.0比38.9±26.7;NMDA受体介导的DR—EPSP的幅度(mV)为4.6±4.3比2.4±3.6;非NMDA受体介导的DR—EPSP的AUC为78.4±53.6比70.5±32.7,均P〈0.053,亦可表现为抑制(DR—EPSP的幅度为1.0±0.6比2.0±0.8,AUC为18.0±13.4比35.1士13.4,均P〈0.01),而在灌流浓度≥3.0μmol/L则仅呈浓度、时间依赖性抑制(3.0μmol/L时DR—EPSP幅度为0.4±0.6比2.0±0.8;30.0μmol/L时DR—EPSP幅度为0.1±0.4比2.0±0.8,均P〈0.01)。结论ET不仅浓度依赖性抑制新生大鼠离体脊髓MN的AP发放,并对感觉传人的突触传递及其介导受体呈现浓度相关的差异性作用。
Objective To investigate the effects of anesthetic ET treatment on afferent sensory-motor transmission in neonatal rat spinal cord ex vivo and the underlying mechanisms. Methods Spinal cord slices from neonatal rats (7 - 14 days postnatal) were treated with ET at different concentrations. The conventional recording techniques for intracellular electrophysiological parameters were employed for the analysis of the dorsal root (DR) electric stimulation elicited excitatory postsynaptic potential (DR-EPSP) in MNs. Results ET concentration-dependently suppressed the action potential (AP) and the frequency of firing in MNs. As compared to un-treated control, at 0. 3, 3.0 (clinical concentration 0. 8 -20. μmol/L) and 30. 0 μmol/L, ET significantly (P〈0. 05 or P〈0. 01) suppressed AP amplitude (mV: 57.5±33.5, 33.8±34.9, 31.2± 34.9 vs. 74. 3 ± 9.4, respectively). At 0. 3 μmol/L, the effect of ET was differential., it significantly (P〈0.05) increased the area under curve (AUC) for DR-EPSP (67.1±43.0 vs. 38.9±26.7), amplitude of N-methyl-D-aspartate (NMDA) receptor-mediated DR-EPSP (4.6 ± 4. 3 vs. 2.4± 3.6), and the AUC of non-NMDA receptor-mediated DR-EPSP (78.4±53.6 vs. 70. 5±32.7), but also reduced (P〈0. 01) the amplitude of DR-EPSP (1.0±0.6 vs. 2. 0±0.8) and the AUC of DR-EPSP (18. 0±13.4 vs. 35.1±13. 4). At concentrations ≥ 3.0 μmol/L, ET effect was totally inhibitory in a concentration-and time-dependent manner: the amplitude of DR-EPSP (as compared to their controls) at 3.0 and 30.0μmol/L were (0. 4± 0. 6 vs. 2.0±0.8) and (0.1±0.4 vs. 2.0±0.8), respectively, both P〈0.01. Conclusion ET can suppress AP and its firing frequency in MNs concentration-dependently in neonatal rat spinal cord ex vivo. At certain concentration, its effect is differential for DR-EPSP and the glutamate receptors mediating the afferents sensory-MN transmission.