不同剂量咪达唑仑与乳化异氟醚对大鼠催眠效应的相互作用  

Hypnotic interaction between midazolam and emulsified isoflurane in rats

作　　者：杨经文[1] 陈本桢[1] 易明量[1] 张文胜[1] 刘进[1] 

机构地区：[1]四川大学华西医院麻醉科,成都市610041

出　　处：《中华麻醉学杂志》2009年第1期21-23,共3页Chinese Journal of Anesthesiology

基　　金：国家自然科学基金资助项目（30271259）

摘　　要：目的评价不同剂量咪达唑仑与乳化异氟醚对大鼠催眠效应的相互作用。方法成年雄性SD大鼠125只，体重240-300g，随机分为5组（n=25），采用改良序贯法进行实验，M组和I组分别经尾静脉注射咪达唑仑、乳化异氟醚，首剂量分别为17．3mg／kg、0．55ml／kg；MI1组、MI2组和MI3组分别经尾静脉注射1／4、1／2、3／4咪达唑仑催眠效应半数有效剂量（ED50）＋乳化异氟醚（首剂量分别为0．22、0．19、0．12ml／kg），各组相邻剂量比值均为0．85，采用改良序贯法计算各组咪达唑仑、乳化异氟醚催眠效应的ED50及其95％可信区间（95％CI）。催眠有效的标准：前爪翻正反射消失。采用等辐射分析法判断不同剂量咪达唑仑与乳化异氟醚催眠效应的相互作用。结果M组咪达唑仑催眠效应的ED50及其95％CI为26（22～30）mg／kg；I组、MI1组、MI2组及MI3组乳化异氟醚催眠效应的ED50及其95％CI分别为0．67（0．61—0．73）、0．30（0．28～0．33）、0．22（0．18～0．26）、0．18（0．16～0．20）ml／kg。MI1组、MI2组、MI3组两药相互作用系数分别为1．51（P〈0．01）、1．21（P〈0．05）、0．98（P〉0．05）。结论咪达唑仑6．5、13mg／kg复合乳化异氟醚时两药的催眠效应为协同作用，咪达唑仑19．5mg／kg复合乳化异氟醚时两药的催眠效应为相加作用。Objective To examine the effects of different doses of midazolam on ED50 of emulsified isoflurane and to determine the type of interaction between them for hypnosis by isobolographic analysis in rats. Methods One hundred and twenty-five adult male SD rats weighing 240-300 g were randomized into 5 groups （ n = 25 each） ： group Ⅰ midazolam （M） ; groupⅡ emulsified isoflurane （I） ; group Ⅲ , Ⅳ, Ⅴ , 1/4, 1/2 and 3/4 ED50 of midazolam for hypnosis ＋ emulsified isoflurane （ MI1 , MI2, MI3 ）. Up-and-down sequential experiment was used to determine ED50 of midazolam and emulsified isoflurane for loss of righting reflex in group Ⅰ - Ⅴ . The intial dose of midazolm was 17.3 mg/kg in group M. The initial doses of emulsified isoflurane （120 mg/ml） were 0.55 （in group I）, 0.22 （MI1 ）, 0.19 （MI2 ） and 0.12 ml/kg （MI3 ） respectively. In group MI1-3 midazolam was injected over 15 seconds and after an interval of 2.5 min emulsified isoflarane was injected over 10 s. ED50 was calculated using Dixon-Mood method. Isobolographic and algebraic analyses were used to determine the type of interaction between midazolam and emulsified isoflarane. Results The five groups were comparable with respect to M/F sex ratio and body weight. The ED50 of midazolam was 26.0 mg/kg in group M. Midazolam 6.5, 13.0 and 19.5 mg/kg were given in group MI1 , MI2 and MI3 respectively. The ED50 of emulsified isoflurane was 0.67 （in group I）, 0.30 （MI1） , 0.22 （MI2） and 0.18 ml/kg （MI3） respectively. The isobolographic analysis indicated that with increasing doses of midazolam, the ED50 of emulsified isoflurane decreased progressively in a non-linear fashion. The isobolographic and algebraic analyses demonstrated that the interaction between midazolam and emulsified isoflurane was synergistic for hypnosis. Conclusion The hypnosis is synergistic when midazolam 6.5,13 mg/kg are combined with emulsified isoflurane and additive when midazolam 19.5 mg/kg is combined with emulsified isoflurane.

关 键 词：麻醉药 吸入 咪达唑仑 剂量效应关系 药物 药物相互作用 催眠术 麻醉 

分 类 号：R614[医药卫生—麻醉学]