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背景:经典的抗癫痫治疗药物苯巴比妥、苯妥英钠、地西泮等均具有抑制大鼠杏仁核的点燃效应,咪达唑仑是否有此效果尚不十分明确。目的:观察咪达唑仑对大鼠杏仁核点燃发作的抑制及其抗癫痫作用及对小鼠最大电休克惊厥模型的影响。设计:分为3个小实验,分别检测咪达唑仑对杏仁核点燃、对自主活动、对惊厥发生率的作用,各小实验采用完全随机,组间对照或动物前后对照。单位:青岛大学医学院。材料:实验于2004-08/2005-03在青岛大学医学院附属医院综合实验室完成。选择雌性Wistar大鼠9只,体质量(250±10)g;昆明种小鼠120只,雌雄不拘,体质量(20±5)g,实验动物由青岛市药品检验所动物中心提供。咪达唑仑由徐州恩华药业生产(批号:20030706,5g/L)。方法:①电极埋置建立大鼠杏仁核点燃模型。随机取点燃大鼠9只,分别以0.25,0.5,1mg/kg咪达唑仑腹腔注射,采用四道生物信号微机处理系统测定后放电时程和Racine’s分级。②将60只小鼠随机分为生理盐水组,苯巴比妥(40mg/kg)组,咪达唑仑0.5,1.0,1.5mg/kg组,每组12只。腹腔注射给药,用XZC-4A小动物自主活动仪测定单位时间内的活动数(次数/5min)。③建立小鼠最大电休克惊厥模型的影响,以及计数惊厥发生率。主要观察指标:咪达唑仑对大鼠后放电时程和Racine’s分级、对小鼠自主活动次数和惊厥发生率的影响。结果:纳入大鼠9只和小鼠120只,全部进入结果分析。①咪达唑仑对大鼠杏仁核点燃发作的影响:咪达唑仑0.5,1.0mg/kg腹腔注射后,后放电时程和Racine’s分级均明显低于用药前(P<0.05～0.01);咪达唑仑0.25mg/kg腹腔注射后,后放电时程低于用药前(P<0.05),Racine’s分级差异不明显(P>0.05)。②咪达唑仑对小鼠自主活动的影响:苯巴比妥组和咪达唑仑0.5,1.0,1.5mg/kg组小鼠自主活动数均明显低于生理盐水组(P<0.01),咪达唑仑0.5mg/kg组小鼠自主活动数高于苯巴比妥组(P<0.05)。③咪达唑仑抗小鼠最大电休克实验的结果:苯巴比妥组和咪达唑仑0.5,1.0,1.5mg/kg组小鼠惊厥发生率均明显低于生理盐水组(P<0.05～0.01),咪达唑仑0.5mg/kg组小鼠惊厥发生率高于苯巴比妥组(P<0.05)。结论:咪达唑仑具有抑制杏仁核点燃的作用,抗癫痫作用显著,具有明确的抗惊厥和镇静作用。
Background: Phenobarbital, phenytoin sodium, diazepam and so on, all of which are classic antiepileptic drugs, can inhibit the lighting effect of amygdala in rats. Whether midazolam has this effect is not yet clear. Objective: To observe the inhibition of midazolam on the onset of amygdala in rats and its antiepileptic effect and its effect on the model of maximal electroshock shock in mice. DESIGN: Divided into 3 small experiments, the effect of midazolam on the amygdala, the effect on autonomic activity and the incidence of convulsions were examined. All the small experiments were completely randomized, and the control group was compared with the control group before and after the experiment. Unit: Qingdao University School of Medicine. Materials: The experiment was performed at the General Laboratory of Affiliated Hospital of Qingdao University Medical College from August 2004 to March 2005. Nine female Wistar rats were selected and their body weight was (250 ± 10) g. 120 Kunming mice were male and female. The body weight was 20 ± 5 g. Experimental animals were provided by Animal Center of Qingdao Institute of Drug Control. Midazolam was produced by Xuzhou Pharmaceutical Co., Ltd. (batch number: 20030706, 5g / L). Methods: (1) Electrode embedding was used to establish the model of amygdala in rats. Nine rats were randomly selected and injected intraperitoneally with 0.25, 0.5 and 1 mg / kg midazolam respectively. The discharge time and Racine’s classification were determined by four-channel biological signal processing system. ② The 60 mice were randomly divided into normal saline group, phenobarbital (40mg / kg) group, midazolam 0.5,1.0,1.5mg / kg group, 12 rats in each group. Intraperitoneal injection, with XZC-4A small animal voluntary activity meter to determine the number of activities per unit time (number / 5min). (3) To establish the mouse model of maximum electroshock shock, and to count the incidence of convulsions. MAIN OUTCOME MEASURES: Effects of midazolam on posterior discharge duration and Racine’s classification in rats, the frequency of spontaneous activity in mice and the incidence of seizures. Results: Nine rats and 120 mice were included in the analysis of the results. (1) The effect of midazolam on the onset of amygdala in rats: Midazolam 0.5,1.0 mg / kg intraperitoneal injection, the discharge duration and Racine’s classification were significantly lower than before treatment (P <0.05 ~ 0.01); After intraperitoneal injection of midazolam 0.25mg / kg, the post discharge time was lower than before treatment (P <0.05), and Racine’s grade was not significantly different (P> 0.05). (2) The effect of midazolam on spontaneous activity in mice: The numbers of spontaneous activity in mice treated with phenobarbital and midazolam were significantly lower than those in the saline group (P <0.01) Midazolam 0.5mg / kg group mice autonomic activity than phenobarbital group (P <0.05). (3) The results of maximal electroshock experiment of midazolam in mice: The incidences of seizures in mice treated with phenobarbital and midazolam were significantly lower than those in the normal saline group (P <0.05) ~ 0.01), midazolam 0.5mg / kg mice seizure incidence was higher than phenobarbital group (P <0.05). Conclusion: Midazolam has the effect of inhibiting amygdala lighting, antiepileptic effect is significant, with clear anticonvulsant and sedation.