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异丙酚、咪达唑仑复合芬太尼对海马锥体神经元γ-氨基丁酸A受体的作用
Effects of propofol or midazolam combined with fentanyl on GABA_A receptor in hippocampal pyramidal neurons of rats
【摘要】 目的研究异丙酚、咪达唑仑分别复合芬太尼对大鼠海马锥体神经元γ-氨基丁酸A(GABAA)受体的作用,探讨复合麻醉的机制。方法采用酶-机械法急性分离出生3~10日龄SD大鼠的海马锥体神经元,采用全细胞膜片钳技术记录锥体神经元GABAA受体介导的Cl-电流(GABA电流,IGABA)。实验分为单纯异丙酚组(组Ⅰ)、异丙酚复合芬太尼组(组Ⅱ)、单纯咪达唑仑组(组Ⅲ)及咪达唑仑复合芬太尼组(组Ⅳ)。结果0.3~30.0μmol/L异丙酚(组Ⅰ、组Ⅱ)、0.03~100.0μmol/L咪达唑仑(组Ⅲ、组Ⅳ)能剂量依赖性地增强IGABA,两药的作用曲线呈钟形,3.0μmol/L时作用最强,与其他浓度的差异有显著性(P<0.05)。0.01μmol/L芬太尼抑制IGABA后,组Ⅱ3.0μmol/L异丙酚增强IGABA的作用较组Ⅰ更明显[电流增强率:组Ⅰ为(127.2±11.2)%,组Ⅱ为(212.5±14.9)%,P<0.05],组Ⅳ3.0μmol/L咪达唑仑的作用较组Ⅲ无明显改变(P>0.05)。结论芬太尼能够增强异丙酚对海马锥体神经元GABAA受体的作用,对咪唑安定的作用无影响。异丙酚、咪达唑仑复合芬太尼可能减轻芬太尼的神经兴奋性不良反应。
【Abstract】 Objective To observe the effects of propofol or midazolam combined with fentanyl on GABA_A receptor in acutely dissociated hippocampal pyramidal neurons of neonatal rats, so as to reveal the possible mechanism of the combined anesthesia. Methods Whole-cell patch-clamp technique was used to record the GABA_A receptor-induced currents (I_GABA) in four groups(n=5 of each), ie, propofol(groupⅠ), propofol combined with fentanyl(groupⅡ), midazolam (groupⅢ) and midazolam combined with fentanyl(groupⅣ). Results 0.3-30.0 μmol/L propofol (groupⅠ,Ⅱ) and 0.03-100.0 μmol/L midazolam (groupⅢ, Ⅳ) facilitated I_GABA with the greatest enhancement at 3.0 μmol/L of each (P<0.05). Following 0.01 μmol/L fentanyl pretreatment for 10 minutes, the facilitation of I_GABA by 3.0 μmol/L propofol increased significantly [(127.2±11.2)% (groupⅠ) vs (212.5±14.9)% (groupⅡ), P<0.05, n=5], whereas the effects of midazolam were not changed by fentanyl pretreatment [(158.2±34.0)% (groupⅢ) vs (116.3±46.0)% (groupⅣ), P>0.05, n=5]. Conclusion Fentanyl can enhance the effects of propofol on GABA_A receptor, but not influence those of midazolam. Propofol or midazolam combined with fentanyl may prevent the neuroexcitatory effects of fentanyl, supporting their use in combination for clinical anesthesia.
【Key words】 Propofol; Midazolam; Fentanyl; GABA_A receptor; Hippocampus; Pyramidal neuron; Whole-cell patch-clamp;
- 【文献出处】 上海医学 ,Shanghai Medical Journal , 编辑部邮箱 ,2005年11期
- 【分类号】R614
- 【被引频次】4
- 【下载频次】170