南方医科大学学报2024，Vol.44Issue(3)：515-522,8.DOI:10.12122/j.issn.1673-4254.2024.03.13
柴胡皂甙a减轻戊四氮诱发的皮质酮抑郁模型小鼠的急性癫痫发作:基于小胶质细胞介导的炎症反应
Saikosaponin a alleviates pentylenetetrazol-induced acute epileptic seizures in mouse models of depression by suppressing microglia activation-mediated inflammation
摘要
Abstract
Objective To explore the inhibitory effect of saikosonin a(SSa)on pentylenetetrazol-induced acute epilepsy seizures in a mouse model of depression and explore the mechanism mediating this effect.Methods Male C57BL/6J mouse models of depression was established by oral administration of corticosterone via drinking water for 3 weeks,and acute epileptic seizures were induced by intraperitoneal injection of a single dose of pentylenetetrazole.The effect of intraperitoneal injection of SSa prior to the treatment on depressive symptoms and epileptic seizures were assessed using behavioral tests,epileptic seizure grading and hippocampal morphology observation.ELISA was used to detect blood corticosterone levels of the mice,and RT-qPCR was performed to detect the pro-and anti-inflammatory factors.Microglia activation in the mice was observed using immunofluorescence staining.Results The mouse model of corticosterone-induced depression showed body weight loss and obvious depressive behaviors with significantly increased serum corticosterone level(all P<0.05).Compared with those with pentylenetetrazole-induced epilepsy alone,the epileptic mice with comorbid depression showed significantly shorter latency of epileptic seizures,increased number,grade and duration of of seizures,reduced Nissl bodies in hippocampal CA1 and CA3 neurons,increased number of Iba1-positive cells,and significantly enhanced hippocampal expressions of IL-1β,IL-10,TNF-α and IFN-γ.Pretreatment of the epileptic mice with SSa significantly prolonged the latency of epileptic seizures,reduced the number,duration,and severity of seizures,increased the number of Nissl bodies,decreased the number of Iba1-positive cells,and reduced the expression levels of IL-1β,IL-10,TNF-α,and IFN-γ in the hippocampus(P<0.05).Conclusion Depressive state aggravates epileptic seizures,increases microglia activation,and elevates inflammation levels.SSA treatment can alleviate acute epileptic seizures in mouse models of depression possibly by suppressing microglia activation-mediated inflammation.关键词
柴胡皂苷a/癫痫/动物模型/共病抑郁Key words
saikosaponin a/epilepsy/animal model/comorbid depression引用本文复制引用
熊一凡,梁小珊,梁晓涛,李伟鹏,钱益啸,谢炜..柴胡皂甙a减轻戊四氮诱发的皮质酮抑郁模型小鼠的急性癫痫发作:基于小胶质细胞介导的炎症反应[J].南方医科大学学报,2024,44(3):515-522,8.基金项目
国家自然科学基金(82374193,82074265),广东省自然科学基金(2020A1515010324,2021A1515011505),广东省中医药重点学科(脑病科)建设项目(20220105)Supported by National Natural Science Foundation of China(82374193,82074265). （82374193,82074265）
