Liu Jian-Xiang, Liu Fu-Rong, Yang Xin-Jie, Wang Yu-Zhi, Chen Dan-Jiao, Xie Qiang-Min, Zeng Ling-Hui
School of Medicine, Zhejiang University City College, Hangzhou 310015, China.
School of Medicine, Zhejiang University City College, Hangzhou 310015, China; College of Pharmaceutical Science, Zhejiang University, Hangzhou 310058, China.
Zhejiang Da Xue Xue Bao Yi Xue Ban. 2015 Jan;44(1):37-42. doi: 10.3785/j.issn.1008-9292.2015.01.006.
To investigate the effect of licorice flavonoid (LF) on kainic acid (KA)-induced seizure in mice and its mechanism.
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.
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).
LF has no significant anti-seizure effect. However, it can decrease epileptogenesis through inhibition of neurogenesis and mossy fiber sprouting.
探讨甘草黄酮(LF)对 kainic 酸(KA)诱导的小鼠癫痫发作的影响及其机制。
成年雄性 ICR 小鼠注射 25 mg/kg KA 诱导颞叶癫痫发作。在癫痫发作诱导前 7 天(预处理)或癫痫发作诱导后 24 小时(后处理)给予 LF 处理 7 天。观察并比较 LF 处理组和溶剂对照组小鼠的急性癫痫发作潜伏期、发作阶段和持续时间。从第 2 天开始,对癫痫持续状态的小鼠进行视频监测,观察其自发性癫痫发作情况,每天监测 10 小时,持续 6 周。分别进行 BrdU 免疫组化分析和 Timm 染色,以检测神经发生和苔藓纤维发芽情况。
LF 处理组和溶剂对照组小鼠在急性癫痫发作潜伏期、发作阶段和持续时间方面未观察到显著差异。KA 诱导的急性癫痫发作导致小鼠出现自发性癫痫发作,且癫痫发作频率随时间增加。LF 预处理和后处理均降低了建模后第 3 周的癫痫发作频率[(0.58±0.15)/天,(0.38±0.38)/天对(1.23±0.23)/天,P<0.05]。此外,KA 诱导的癫痫发作导致强烈的神经发生和苔藓纤维发芽,但在 KA 注射前后给予 LF 处理均显著抑制了神经发生(15.6±2.6,17.1±3.1 对 28.9±3.5,P<0.05)和苔藓纤维发芽(1.33±0.31,1.56±0.42 对 3.0±0.37,P<0.05)。
LF 无显著的抗癫痫发作作用。然而,它可以通过抑制神经发生和苔藓纤维发芽来减少癫痫发生。