γ-氨基丁酸受体和甘氨酸受体在大鼠丙泊酚麻醉中的作用

The role of GABA receptor and glycine receptor in propofol anesthesia

目的研究丙泊酚对大鼠海马CA1区电刺激诱发兴奋性突触后电流(EPSC)的影响,分析γ-氨基丁酸(GABA)受体和甘氨酸受体在丙泊酚麻醉中的作用。方法断头法分离wistar大鼠(13～19d)海马半脑,切出400μm厚度的海马脑片,全细胞膜片钳技术记录CA1区锥体神经元EPSC。80张脑片分为八组:脂肪乳剂组,50μmol/L丙泊酚组,100μmol/L丙泊酚组,200μmol/L丙泊酚组,SR95531组,士的宁组,SR95531+100μmol/L丙泊酚组,士的宁+100μmol/L丙泊酚组,每组10张。SR95531+100μmol/L丙泊酚组和士的宁+100μmol/L丙泊酚组先在循环液中加入10μmol/LSR95531或4μmol/L士的宁预孵脑片30min。八组均记录基础EPSC10min,然后加入不同药物,继续记录EPSC40min。膜钳制电压为-70mV。结果脂肪乳剂、SR95531和士的宁对EP-SC幅值无影响;丙泊酚呈剂量依赖性的抑制EPSC幅值,50、100、200μmol/L丙泊酚最大抑制EPSC幅值为14.4%、52.3%、67.8%;SR95531+100μmol/L丙泊酚组加入丙泊酚后,EPSC幅值基本无改变;士的宁+100μmol/L丙泊酚组加入丙泊酚后,EPSC幅值仍然下降,最大抑制程度为34.7%。结论丙泊酚主要通过增强GABAA受体功能使兴奋性突触活动降低,甘氨酸受体在其中起到协同和调节作用。

Objective To investigate the effects of propofol on the whole-cell excitatory postsynaptic current（EPSC） in hippocampal CA1 pyramidal neurons and analyze the role of GABAA receptor and glycine receptor in propofol anesthesia. Methods Wistar rats（13-19 d） were killed by cervical dislocation and hippocampal slices（400 μm） were prepared. EPSCs were recorded by whole-cell patchclamp technique. The slices（n = 80） were divided into eight groups. After 10 min baseline of EPSCs was recorded, different drugs were administered in perfusion for another 40 min. In the gabazine with 100 μmol/L propofol group and the strychnine with 100 μmol/L propofol group, hippocampal slices were incubated with gabazine or strychnine for 30 min before recording. The holding potential was -70 mV. Results Intralipid,SR95531 and strychnine did not change the amplitude of EPSC,but 50, 100 and 200 μmol/L propofol reduced EPSC by 14.4% ,52.3% and 67.8% ,respectively. After hippocampal slices were incubated with gabazine, 100 μmol/L propofol did not decrease EPSC. However, after hippocampal slices were incubated with strychnine, 100 μmol/L propofol still reduced the amplitude of EPSC by 34.7%. Conclusion Propofol could potentiate the function of GABAA receptor and inhibit excitatory transmission. Glycine receptor may regulate the action of GABAA receptor in the CA1 of hippocampus.