中文摘要：

目的观察静脉麻醉药咪达唑仑（MID）对四亚甲基二酰四胺（毒鼠强,TETs）诱发癫痫持续状态（SE）的抑制作用及其对皮质和海马GABAA受体α1亚单位表达的影响。方法60只SD大鼠随机分为为正常对照组、阳性对照组、癫痫发作组及咪达唑仑10、20、30mg/kg组,每组10只。建立TETs诱发大鼠癫痫持续状态模型,以脑电图上典型癫痫波的变化及动物24h存活数为观察指标,比较腹腔注射不同剂量咪达唑仑（10、20、30mg/kg）的抗惊疗效,以地西泮（安定）作为阳性对照药。同时以蛋白印迹法（Westernblotting）观察20mg/kg咪达唑仑对SE大鼠发作24h后皮质和海马GABAA受体α1亚单位表达的影响。结果1.2mg/kgTETs能诱发大鼠明显的SE发作,EEG显示持续的高幅高频惊厥波,20及30mg/kg咪达唑仑均可有效控制惊厥发生,给药10min后EEG上的高幅惊厥棘波幅度及频率均明显降低,1h后高幅惊厥棘波完全消失,持续观察5h未见高幅惊厥棘波出现。咪达唑仑20及30mg/kg组动物24h存活数明显高于癫痫发作组（P〈0.01）。咪达唑仑10mg/kg组在EEG上仍可见高幅惊厥棘波出现,且动物24h存活数与阳性对照组比较无显著差异。Western blotting结果显示,SE发作后24h大鼠皮质和海马GABAA受体α1亚单位表达与阳性对照组比较显著降低（P〈0.01）,而咪达唑仑20mg/kg组其表达明显增加,与正常对照组及SE组比较均显著升高（P〈0.01）。结论咪达唑仑对TETs诱发的SE具有确切治疗作用,可用作临床的一线或二线用药,其抗惊厥作用可能与GABAA受体α1亚单位表达增加有关。

英文摘要：

Objective To observe the inhibitory effect of midazolam on status epilepticus （SE） induced by tetramine in rats and its influence on expression of GABAA receptor α1 subunit in cortex and hippocampus. Methods Sixty SD rats were randomly divided into 6 groups （10 each）., normal control group, positive control group, SE group, and midazolam 10, 20, 30mg/kg groups. SE was induced by tetramine （1.2mg/kg） in rat, and its typical epileptic waves and survival rate of rats served as observation indexes. The anti-epileptic effects of different dosages of midazolam （10, 20, 30mg/kg） injected intraperitoneally were observed. Diazepam was employed as the positive control drug. The effect of 20mg/kg midazolam on the expression of GABAA receptor α1 subunit in the cortex and hippocampas 24h after seizures was determined by Western blotting. Results 1.2mg/kg tetramine could readily induce SE, with EEG showing high-frequency and high-amplitude spike waves continuously. 20 and 30mg/kg midazolam alleviated the seizure effectively, with the frequency and amplitude of eclampsia waves degraded significantly 10min after midazolam administration. Eclampsia waves disappeared lh after midazolam administration without reappearance within 5 hours. The survival rates of midazolam 20 and 30mg/kg groups were obviously higher than that of SE group （P〈0. 01）. In rnidazolam 10mg/kg group, the high-frequency and high-amplitude eclampsia waves could still be observed, and the survival rate was similar to that of SE group （P〉0. 05）. The expression of GABAA receptor α2 subunit was significantly down regulated in cortex and hippocampus 24 hours after SE occurrence, and increased significantly in midazolam 20mg/kg group, and it was higher than that of normal control group and SE group （P〈0.01）. Conclusion Midazolam can efficiently inhibit the seizure of status epilepticus induced by tetramine, and may used as first or second line drug in clinical practice. The efficacy of midazolam may be attributable to the up-regul