丙泊酚对大鼠海马CA1区兴奋性突触传递的影响

The effects of propofol on excitatory synaptic transmission in hippocampal CA1 neurons of rats

目的观察500μmol/L丙泊酚对大鼠海马CA1区电刺激诱发的兴奋性突触后电流(EPSC)的影响,分析丙泊酚的可能作用机制。方法断头法分离Wistar大鼠(13~19d)海马半脑,用切片机切出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。实验分两组:脂肪乳剂组(n=6)和丙泊酚组(n=10)。先以50μmol/L印防己毒素预孵脑片30min后,记录基础EPSC10min,然后加入450μl脂肪乳剂或丙泊酚(相当于500μmol/L),继续记录EPSC40min;继而以配对刺激代替单刺激,观察EPSC2/EPSC1比率的变化;改变膜钳制电压(-80^+60mV),观察电流-电压(I-V)曲线的变化。结果脂肪乳剂对EPSC无影响,500μmol/L丙泊酚降低大鼠海马CA1区EPSC值,25~30min左右达最大抑制效果,EPSC幅值下降至基础值的67·5%,明显低于脂肪乳剂组(P<0·05);而且500μmol/L丙泊酚明显降低EPSC2/EPSC1比率,也使I-V曲线左移,降低反转电位至-35mV左右。结论500μmol/L丙泊酚对大鼠海马CA1区兴奋性突触传递产生抑制作用,这可能与其增强突触前膜、突触后膜GABAA受体活性有关。

Objective To investigate the effects of 500μmol/L propofol on the whole-cell excitatory postsynaptic current(EPSC) in hippocampal CA1 pyramidal neurons of rats and to analyze the mechanisms of propofol deeply.Methods Wistar rats(13-19d) were killed by cervical dislocation and hippocampal slices(400μm) were prepared.EPSCs were recorded by whole-cell patch-clamp technique.The experiments were divided into two groups: the intralipid group(n=6) and the propofol group(n=10).After hippocampal slices were preincubated with 50μmol/L picrotoxin for 30min,the base value was recorded for 10min and then 450μl intralipid or propofol(500μmol/L) was applied in perfusion for another 40min.The Schaffer collateral/commissural pathway was stimulated with pair-pulses(interpulse interval was 50ms) and the EPSC2/EPSC1 ratio was analyzed.Moreover,the holding potential was changed from -80 to +60mV and the current-voltage curve was drawn. Results Intralipid didn’t affect EPSC,but 500μmol/L propofol reduced EPSC to (67.5±1.7)% of the base value after application of propofol. 500μmol/L propofol decreased the EPSC2/EPSC1 ratio and shifted the current-voltage curve to the left. Conclusion 500μmol/L propofol inhibits excitatory synaptic transmission in hippocampal CA1 pyramidal neurons of rats. The activity of GABA_A receptor in the presynaptic and postsynaptic membrane may be increased with propofol applied.