依托咪酯和咪达唑仑对小鼠海马脑片细胞外信号调节激酶ERK1/2磷酸化水平的影响

Effects of Etomidate and Midazolam on Extracellular Signal-regulated Kinase1/2 Phosphorylation in Mice Hippocampal Slices

目的观察依托咪酯和咪达唑仑对小鼠海马脑片细胞外信号调节激酶ERK1／2磷酸化水平的影响。方法BALB／C小鼠，雌雄不拘，取其海马制成厚450μm脑片，分别应用10^-9～10^-4mol／L依托咪酯和咪达唑仑在36℃恒温条件下孵育1h。应用SDS-PAGE和Western blot等技术，用GelDoe凝胶成像系统，半定量检测小鼠海马内p-ERK1／2的磷酸化水平。结果与对照组比较，在本研究应用的浓度范围内，咪达唑仑浓度的增加对ERK1／2磷酸化抑制程度无明显影响；在本研究所应用的浓度范围内，依托咪酯浓度的增加对ERK1磷酸化抑制程度无明显影响。随着依托咪酯浓度的增加，对ERK2磷酸化的抑制程度逐渐增加。结论依托咪酯和咪达唑仑可抑制小鼠海马脑片细胞外信号调节激酶ERK1／2磷酸化水平。在本研究应用的浓度范围内，随浓度的增加，依托咪酯对ERK2磷酸化水平的抑制程度逐渐增加。

Objective To investigate the effects of etomidate and midazolam on extracellular signal-regulated kinase1/2 phosphorylation in mice hippocampus slices. Methods BALB/C mice weighting 18-22 g were decapitated and the hippocampus were dissected. Hippocampal slices were prepared with Mac 11 wain tissue chopper. Hippocampal slices were incubated at 36℃ during the whole experiment. The slices were incubated with 10^-9-10^-4 mol/L etomidate and midazolam respectively for 1h during the experiment. Phosphorylation of ERK1/2 was examined in hippocampus slices by immunohlotting with both phosphorp44/42 Map kinase and p44/42 Map kinase antibodies. Experiments were performed in the absence （control） or presence of various concentrations of etomidate and midazolam. Results Clinically relevant concentrations of etomidate and midazolam decrease phosphorylation of ERK1/2. The decrease was concentration-dependent. Conclusion Etomidate and midazolam markedly decrease phosphorylation of ERK1/2 in mice hippocampal slices.