咪达唑仑和氟马西尼对异丙酚麻醉小鼠大脑皮质环腺苷酸含量的影响

Effects of intraperitoneal injections of midazolam and flumazenil on the content of cyclic denosine monophosphate in the cerebral cortex of propofol-anesthetized mice

目的 了解γ -氨基丁酸A型受体上苯二氮位点激动剂咪达唑仑 (Mid)和 (或 )其拮抗剂氟马西尼 (3-羟甲基 - β -咔啉 ,FZ)对小鼠静脉注射异丙酚时不同时程大脑皮质cAMP含量的影响。 方法 昆明种小鼠 6 4只 ,随机分为 4组。分别在腹腔注射生理盐水 (NS) 10ml kg、咪达唑仑 1mg kg和 (或 )氟马西尼 0 .5mg kg后 8min ,静脉注射 2 0mg kg异丙酚 (Prop) ,于翻正反射消失时及翻正反射恢复 40min时断头取脑 ,并记录翻正反射消失持续时间。结果 Mid +Prop组和Mid +FZ +Prop组与NS +Prop组相比小鼠翻正反射消失持续时间明显延长 (P <0 .0 1) ;2组相比 ,后者有明显缩短 (P <0 .0 5 )。NS +Prop组、Mid +Prop组、FZ +Prop组及Mid +FZ +Prop组翻正反射消失时大脑皮质cAMP含量分别是翻正反射恢复 40min时的 134 .3%、12 9.8%、12 5 .2 %和 12 5 .1% ,均明显升高(P <0 .0 5 ) ;在翻正反射消失这一时点 ,Mid +Prop组小鼠大脑皮质cAMP含量为NS +Prop组的 115 .7% ,有升高倾向 ,但无统计学意义 (P >0 .0 5 )。结论 行为学上 ,咪达唑仑和异丙酚具有协同效应 ,氟马西尼可部分拮抗该效应 ;静脉注射异丙酚时大脑皮质cAMP含量的升高 ,在其全麻机制中可能发挥重要作用 ;

Objective To investigate the effects of intraperitoneal injections of midazolam (Mid) and flumazenil (FZ) on the cAMP content of cerebral cortex in the mice anesthetized with propofol (Prop).?Methods Sixty-four mice were divided randomly into four groups. NS (10 ml/kg) , Mid (1 ml/kg) or/and FZ (0.5 mg/kg) were administered intraperitoneally respectively. 8min later, Prop (20 mg/kg) was administered intravenously to all of the mice. Their behavioral manifestations were noticed to record the duration of loss of righting reflex. Half of the mice in each group were decapitated at the time of loss of righting reflex, and the other half were killed 40 min after the recovery of righting reflex, to measure the cAMP content of cerebral cortex by competitive protein binding assay.Results As compared with NS+Prop group, the time of loss of righting reflex in Mid+Prop and Mid+FZ+Prop groups was prolonged significantly by 68% and 52% respectively ( P <0.01). The time of loss of righting reflex in Mid+FZ+Prop group was less than in Mid+Prop group by 43% ( P <0.05). The cerebrocortical cAMP contents measured at the time of loss of righting reflex were higher than those measured 40 min after the recovery of righting reflex in the NS+Prop, Mid+Prop, FZ+Prop and Mid+FZ+Prop groups by 34.4%, 29.8%, 25.2% and 25.1% respectively ( P <0.05).The cerebrocortical cAMP content in the Mid+Prop group was higher than that in the NS+Prop group at the time of loss of righting reflex by 15.7%,but the difference was of no significance ( P >0.05).?Conclusions Midazolam and propofol have synergism in action, which can be partially antagonized by flumazenil. The increase of cAMP content in the cerebral cortex may play an important role in the propofol-induced general anesthesia. Intraperitoneal midazolam and/or flumazenil do not affect the changes of cerebrocortical cAMP content in mice under propofol anesthesia.