致死剂量N-甲基-D-天冬氨酸中毒模型小鼠对丙泊酚的反应*☆

背景：丙泊酚具有较好的抗惊厥作用，但其作用机制尚不清楚。 目的:观察丙泊酚对致死剂量N-甲基-D-天冬氨酸中毒模型小鼠的行为学及存活率的影响。 方法：建立N-甲基-D-天冬氨酸致死模型昆明小鼠，给药前10 min，腹腔注射丙泊酚12.5，25，50，75，100 mg/kg，观察中毒小鼠的行为学改变及存活率，阳性对照组在造模前腹腔注射非特异性的N-甲基-D-天冬氨酸受体拮抗剂地佐环平 2 mg/kg，为排除丙泊酚溶剂脂肪乳可能的作用，设定了脂肪乳组，在造模前腹腔注射等容积的脂肪乳作为对照。 结果与结论：腹腔注射N-甲基-D-天冬氨酸175 mg/kg可导致小鼠全身惊厥发生并且很快死亡，而提前给予丙泊酚12.5，25，50，75，100 mg/kg后，可见其可剂量依赖性的对抗小鼠惊厥的发生，并降低小鼠的死亡率，地佐环平(2 mg/kg)可完全预防惊厥发生，而脂肪乳不能抑制惊厥的发生，对致死剂量N-甲基-D-天冬氨酸中毒模型小鼠无保护作用。提示丙泊酚的抗惊厥作用可能与N-甲基-D-天冬氨酸受体有关。

Protective effects of propofol on a mouse model of toxicity induced by lethal dose of N-methyl-D-aspartate

BACKGROUND: Propofol exhibits good anticonvulsive effects, but the potential mechanism remains poorly understood. OBJECTIVE: To investigate the effects of profofol on the ethological changes and survival rate of mouse models with toxicity induced by lethal dose of N-methyl-D-aspartate (NMDA). METHODS: Kunming mouse models of toxicity-induced by NMDA were established. Before NMDA administration, propofol was subcutaneously administered at a dose of 12.5, 25, 50, and 100 mg/kg. The ethological changes and survival rate of toxic mice were observed. The positive control group mice were subcutaneously administered nonspecific NMDA receptor antagonist MK801 (2 mg/kg). A fat milk group was set and the same amount of fat milk was subcutaneously administered as control. RESULTS AND CONCLUSION: NMDA at a dose of 175 mg/kg resulted in general seizure, and made all mice die within 10 minutes after convulsion. When 12.5, 25, 50, 75 and 100 mg/kg propofol was intraperitoneally administrated to mice within 10 minutes before NMDA injection, convulsion rate was decreased and survival rate was increased, in a dose-dependent manner. MK801 (2 mg/kg) could completely prevent convulsion, while fat milk could not produce protective effects on lethal dose of NMDA-induced toxicity in mice. These results showed that the anticonvulsive effect of propofol is possibly related to NMDA receptor.