南方医科大学学报

南方医科大学学报 ›› 2024, Vol. 44 ›› Issue (3): 515-522.doi: 10.12122/j.issn.1673-4254.2024.03.13

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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

熊一凡，梁小珊，梁晓涛，李伟鹏，钱益啸，谢 炜   

  1. 南方医科大学中医药学院，广东 广州 510515；南方医科大学南方医院中医科，广东 广州 510515；广州市荔湾固生堂中医门诊部，广东 广州 510250
  • 出版日期:2024-03-20 发布日期:2024-04-03

Saikosaponin a alleviates pentylenetetrazol-induced acute epileptic seizures in mouse models of depression by suppressing microglia activation-mediated inflammation

XIONG Yifan, LIANG Xiaoshan, LIANG Xiaotao, LI Weipeng, QIAN Yixiao, XIE Wei   

  1. School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, China; Department of Traditional Chinese Medicine, Nanfang Hospital of Southern Medical University, Guangzhou 510515, China; Guangzhou Liwan Gushengtang Traditional Chinese Medicine Clinic, Guangzhou 510250, China
  • Online:2024-03-20 Published:2024-04-03

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摘要： 目的 探讨柴胡皂甙a（SSa）对皮质酮（CORT）抑郁模型基础上诱发小鼠急性癫痫的干预作用及机制。方法 选用雄性SPF C57BL/6J小鼠，使用皮质酮口服给药，制备CORT抑郁模型，之后予戊四氮诱发小鼠急性癫痫发作，并腹腔注射柴胡皂苷a进行干预。根据干预方式的不同将小鼠分成对照组、Epilepsy组、Epilepsy+SSa组、CORT+Epilepsy、CORT+Epilepsy+SSa组，6只/组。利用旷场实验、十字高架实验、强迫游泳实验、糖水偏好实验评估抑郁相关指标，通过ELISA实验检测血皮质酮含量；采用痫性发作分级、海马形态学评估癫痫发作程度；RT-qPCR检测炎症相关因子、免疫荧光实验观察小胶质细胞活化情况。结果 成功构建皮质酮诱导的小鼠抑郁模型，小鼠的体质量、糖水偏好率、旷场的总路程、中央格停留时间和路程、开放臂进入次数和开放臂停留时间百分比均降低（P<0.05），强迫游泳不动时间和血清CORT含量增加（P<0.05）；与Epilepsy组相比，CORT+Epilepsy组小鼠痫性发作潜伏期缩短，发作次数、发作等级以及发作持续时间都明显增加（P<0.05），海马CA1、CA3区神经元Nissl体表达减少，Iba1阳性细胞的数量增多，同时，海马中IL-1β、IL-10、TNF-α、IFN-γ的表达水平升高。SSa干预后，Epilepsy+SSa组和CORT+Epilepsy+SSa组的癫痫发作潜伏期均延长，发作次数、发作持续时间、发作级别均减少（P<0.05），海马CA1、CA3区神经元的Nissl小体数量均增加、Iba1阳性细胞的数量均有所减少，海马中IL-1β、IL-10、TNF-α、IFN-γ的表达水平均降低（P<0.05）。结论 抑郁状态加重了癫痫发作、小胶质细胞活化及炎症水平更高，而柴胡皂甙a可能通过调节小胶质细胞介导的炎症激活，减轻抑郁合并癫痫小鼠的发作。

关键词: 柴胡皂苷a；癫痫；动物模型；共病抑郁

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.

Key words: saikosaponin a; epilepsy; animal model; comorbid depression