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目的在大鼠最大电休克发作(MES)及戊四唑惊厥(MST)模型上,比较评价咪达唑仑与地西泮经鼻给药的抗惊厥作用。方法大鼠随机分为7组,分别为模型组、咪达唑仑鼻喷剂低、中、高剂量组和地西泮鼻喷剂低、中、高剂量组,每组10只。建立MES及MST模型,评价不同剂量咪达唑仑经鼻给药的抗惊厥作用,并与经典抗癫痫药物——地西泮比较,观察给药后72 h各组动物海马、皮质及杏仁核组织病理学变化。结果不同剂量咪达唑仑经鼻预防给药,均可剂量依赖性地对抗MES及MST;在等剂量给药条件下,其抗惊厥作用明显优于地西泮(P<0.05或P<0.01)。病理学结果显示,咪达唑仑与地西泮经鼻预防给药均可减轻癫痫所致海马、皮质及杏仁核神经元细胞的损伤,抑制小胶质细胞增多及炎性细胞浸润,细胞核固缩以及嗜神经现象减少。结论咪达唑仑经鼻给药,在经典癫痫模型上均具显著抗惊厥作用,并可显著抑制癫痫所致脑损伤。
Objective To compare the anticonvulsant effect of nasal administration of midazolam and diazepam on rats with maximal electroshock attack (MES) and pentylenetetrazole convulsion (MST) model. Methods The rats were randomly divided into 7 groups: model group, midazolam nasal spray low, medium and high dose group and diazepam nasal spray low, medium and high dose group, 10 rats in each group. MES and MST models were established to evaluate the anticonvulsant effect of nasal administration of midazolam in different doses. Compared with the classic antiepileptic drug diazepam, 72 h after administration, hippocampus, cortex and amygdala Histopathological changes. Results Midazolam administered at different dosages could antagonize MES and MST in a dose-dependent manner. Compared with diazepam (P <0.05 or P <0.01) ). Pathological results show that midazolam and diazepam nasal prophylaxis can reduce epilepsy-induced neuronal damage in the hippocampus, cortex and amygdala, inhibition of microglia and inflammatory cell infiltration, nuclear Reduction and reduction of neuropathic phenomena. Conclusion Nasal administration of midazolam has a significant anticonvulsant effect on the classic epilepsy model and can significantly inhibit brain injury induced by epilepsy.