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.