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

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

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10min,腹腔注射丙泊酚12.5,25,50,75,100mg/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2mg/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175mg/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12.5,25,50,75,100mg/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(2mg/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。

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.