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

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240～300 g,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17.3 mg/kg、0.55 ml/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、0.12 ml/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、MI1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(P0.05).结论 咪达唑仑6.5、13 mg/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19.5 mg/kg复合乳化异氟醚时两药的催眠效应为相加作用.

Hypnotic interaction between midazolam and emulsified isoflurane in rats

Objective To examine the effects of different doses of midazelam on ED50 of emulsified isoflurane and to determine the type of interaction between them for hypnosis by isobelographic 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 Ⅰmidazolam (M); group Ⅱ emulsified isnflurane (Ⅰ); group Ⅲ ,Ⅳ ,Ⅴ, 1/4, 1/2 and 3/4 ED50 of midazelam for hypnosis + emulsified isoflurane (MI1 , MI2, MI3). Up-and-down sequential experiment was used to determine ED50of 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 isoflurane was injected over 10 s. ED50 was calculated using Dixon-Mood method. Isebolographic and algebraic analyses were used to determine the type of interaction between midazolam and emulsified isoflurane. Results The five groups were comparable with respect to M/F sex ratio and body weight. The Edso 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 (ingroup 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 Edw 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.