The Protective Effect of Aucubin from Eucommia ulmoides Against Status Epilepticus by Inducing Autophagy and Inhibiting Necroptosis
The Protective Effect of Aucubin from Eucommia ulmoides Against Status Epilepticus by Inducing Autophagy and Inhibiting Necroptosis
复制标题
杜仲桃叶珊瑚苷诱导自噬和抑制坏死性凋亡对癫痫持续状态的保护作用
DOI：
10.1142/s0192415x17500331
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发表时间：
2017-01-01
影响因子：
5.7
通讯作者：
Hu, Kai
中科院分区：
文献类型：
--
作者：
Wang, Jin;Li, Ying;Hu, Kai
杜仲叶是一种具有抗氧化应激能力和神经保护作用的著名中药。桃叶珊瑚甙是杜仲的主要化学成分。本研究旨在通过建立锂-匹罗卡品诱发的癫痫持续状态（SE）大鼠模型，探讨桃叶珊瑚甙对海马神经元的抗癫痫作用。在注射锂-匹鲁卡品之前，通过管饲法施用桃叶珊瑚苷（分别以5 mg/kg和10 mg/kg的低剂量和高剂量）两周。在SE诱导后4、24和72 h处死大鼠。桃叶珊瑚苷低、高剂量组均能显著减少SE后DG、门、CA 1、CA 3区死亡神经元数（p <0.05），增加存活神经元数（p < 0.05）。同时，其显著抑制海马中的坏死性凋亡蛋白（MLKL和RIP-1）（p < 0.05或p < 0.01），并增强海马中的自噬蛋白（Beclin-1和LC 3BII/LC 3BI）的流行（p < 0.05或p < 0.01）。总之，桃叶珊瑚苷似乎可以改善锂-匹罗卡品诱导的海马SE中的损伤，减少凋亡神经元的数量，并通过诱导自噬和抑制坏死性凋亡来增加存活神经元的数量。这些发现为进一步研究桃叶珊瑚甙对癫痫相关神经元损害的治疗作用提供了重要依据。
Eucommia ulmoides Oliv. is a famous traditional Chinese medicine which exhibits anti-oxidative stress ability and neuro-protective effects. Aucubin is the predominant component of Eucommia ulmoides Oliv. Our present study is intended to investigate aucubin's potential protective effects on neurons against epilepsy in the hippocampus by establishing the lithium-pilocarpine induced status epilepticus (SE) rat model in vivo. Aucubin (at a low dose and a high dose of 5 mg/kg and 10 mg/kg, respectively) was administered through gavage for two weeks before lithium-pilocarpine injection. Rats were sacrificed at 4, 24 and 72 h after SE induction. Pretreatment with both low-dose and high-dose aucubin significantly reduced the number of death neurons (p < 0.05) and increased the number of surviving neurons (p < 0.05) in DG, Hilus, CA1 and CA3 hippocampal regions post SE. Meanwhile, it significantly inhibited necroptosis proteins (MLKL and RIP-1) (p < 0.05 or p < 0.01) and enhanced autophagy protein (Beclin-1 and LC3BII/LC3BI) prevalence in the hippocampus (p < 0.05 or p < 0.01). In conclusion, aucubin appeared to ameliorate damages in lithium-pilocarpine induced SE in hippocampus, reduce the number of apoptotic neurons, and increased the number of survival neurons by inducing autophagy and inhibiting necroptosis. These original findings might provide an important basis for the further investigation of the therapeutic role of aucubin in treatment or prevention of epilepsy-related neuronal damages.