甘草黄酮对红藻氨酸致痫小鼠的抗癫痫作用研究  

Effect of licorice flavonoids on kainic acid-induced seizure in mice

作　　者：刘健翔[1] 刘福荣[1,2] 杨鑫杰 王昱植 陈丹娇 谢强敏[2] 曾玲晖[1] 

机构地区：[1]浙江大学城市学院医学院,浙江杭州310015 [2]浙江大学药学院,浙江杭州310058

出　　处：《浙江大学学报（医学版）》2015年第1期37-42,共6页Journal of Zhejiang University(Medical Sciences)

基　　金：杭州市科技发展计划(20100333T24);浙江省科技厅实验动物平台(2013C37026)

摘　　要：目的：明确甘草黄酮对红藻氨酸致痫小鼠在急性痫性发作期和自发性癫痫发作期的作用，并从神经元再生和苔藓纤维发芽探讨其可能机制。方法：雄性成年ICR小鼠经腹腔内单次注射红藻氨酸25 mg／kg诱导急性痫性发作，在红藻氨酸致痫前7 d（预防性给药）或致痫后24 h始（治疗性给药）给予小鼠甘草黄酮混合物灌胃（每天1次，连续7 d）。观察急性痫性发作的潜伏期、发作程度及持续时间；模型小鼠第2天起采用录像监控自发性癫痫的发作，一共6周；BrdU免疫组织化学和Timm染色分别检测神经元再生和苔藓纤维发芽。结果：预防性甘草黄酮低中高剂量给药对模型小鼠急性痫性发作的潜伏期、发作程度和发作持续时间均无明显影响；而甘草黄酮预防性用药和治疗性用药从造模后第三周起均能减少模型小鼠自发性癫痫发作频率[（0．58±0．15）次／d 和（0．38±0．38）次／d 与（1．23±0．23）次／d， P＜0．05）]。同时，甘草黄酮预防性和治疗性用药均能减少模型小鼠脑组织神经元再生（15．6±2．6和17．1±3．1与28．9±3．5， P＜0．05）和苔藓纤维发芽（1．33±0．31和1．56±0．42与3．0±0．37， P＜0．05）。结论：甘草黄酮对癫痫急性发作无影响，但对自发性癫痫形成具有一定防治作用，该作用可能与减少神经元再生和苔藓纤维发芽有关。Objective：To investigate the effect of licorice flavonoid （ LF） on kainic acid （ KA）-induced seizure in mice and its mechanism .Methods：Male adult ICR mice were injected with 25 mg/kg KA to induce temporal lobe seizure .LF was administrated 7 d before seizure induction （ pre-treatment ） or 24 h after seizure induction （ post-treatment） for 7 d.Acute seizure latency , seizure stage and duration were observed and compared between LF-and vehicle-treated mice. From d2 on, mice with status epilepticus were video-monitored for spontaneous seizures , 10 h/d for 6 w. Immunohistochemical analysis of BrdU and Timm staining was conducted to detect the neurogenesis and mossy fiber sprouting , respectively .Results：No significant difference was observed in acute seizure latency , seizure stage and duration between LF-and vehicle-treated mice . KA-induced acute seizure resulted in spontaneous seizure in mice, and the seizure frequency was increased with time .Pre-and post-treatment with LF decreased seizure frequency from w3 after modeling [（0.58 ±0.15）/d, （0.38 ± 0.38）/d vs （1.23 ±0.23）/d, P〈0.05].Furthermore, KA-induced seizure resulted in robust neurogenesis and mossy fiber sprouting , while treatment with LF both pre-and post-KA injection significantly inhibited neurogenesis （15.6 ±2.6, 17.1 ±3.1 vs 28.9 ±3.5, P〈0.05） and mossy fiber sprouting （1.33 ±0.31, 1.56 ±0.42 vs 3.0 ± 0.37, P〈0.05）.Conclusion：LF has no significant anti-seizure effect.However, it can decrease epileptogenesis through inhibition of neurogenesis and mossy fiber sprouting .

关 键 词：红藻氨酸/毒性 癫痫/药物疗法 甘草黄酮/药理学 神经元/细胞学 神经再生 苔藓纤维 海马/病理学 疾病模型 动物 

分 类 号：R742.1[医药卫生—神经病学与精神病学]