Vitamin E Exerts Neuroprotective Effects in Pentylenetetrazole Kindling Epilepsy via Suppression of Ferroptosis.
Vitamin E Exerts Neuroprotective Effects in Pentylenetetrazole Kindling Epilepsy via Suppression of Ferroptosis.
复制标题
维生素 E 通过抑制铁死亡对戊四唑引发的癫痫发挥神经保护作用。
DOI：
10.1007/s11064-021-03483-y
复制
发表时间：
2021
影响因子：
4.4
通讯作者：
Jianmin Li
中科院分区：
文献类型：
--
作者：
Xinfan Zhang;Shuhua Wu;Chong Guo;Ke Guo;Zhongbo Hu;Jiangtao Peng;Zhao Zhang;Jianmin Li
癫痫是最常见的慢性神经系统疾病之一。越来越多的证据表明，铁性下垂在癫痫的发生和发展中起着重要作用。维生素E是一种常见的脂溶抗氧化剂，可以调节铁性下垂。本研究旨在探讨维生素E对癫痫大鼠海马神经元铁下垂的影响。雄性SD大鼠64只，随机分为对照组、戊四氮(35 mg/kg)组、维生素E(200 mg/kg)+戊四氮组、铁抑素-1组(FeR-1；2.5Mol/kg)+戊四氮组，每隔一天给药15次，共29d。观察并记录动物的行为学表现(癫痫评分、潜伏期、30min内癫痫发作次数)和脑电变化。尼氏染色和电生理记录分别检测海马CA1区神经元损伤和兴奋性。用分光光度法检测大鼠海马铁、谷胱甘肽(GSH)和丙二醛(MDA)含量。免疫荧光染色检测脂氧合酶15(15-LOX)的表达。Western印迹法检测谷胱甘肽过氧化物酶4(Gpx4)和15-LOX蛋白水平。在PTZ点燃的癫痫模型中，维生素E治疗与癫痫分级、癫痫潜伏期和癫痫发作次数减少有关。维生素E处理还降低了15-LOX的表达，抑制了丙二醛和铁的积累，增加了Gpx4和GSH的表达。综上所述，维生素E可以通过抑制15-LOX的表达来减少神经元性铁下垂和癫痫发作。
Epilepsy is one of the most common chronic neurological diseases. There is increasing evidence for ferroptosis playing an important role in the occurrence and development of epilepsy. Vitamin E is a common fat-soluble antioxidant that can regulate ferroptosis. The aim of this study was to investigate the effects of vitamin E on ferroptosis of hippocampal neurons in epileptic rats. Sixty-four male Sprague-Dawley (SD) rats were randomly divided into control, pentylenetetrazol (PTZ; 35mg/kg), vitamin E (200mg/kg) + PTZ, and Ferrostatin-1 (Fer-1; 2.5μmol/kg) + PTZ groups, with drugs administered intraperitoneally 15 times every other day for 29days. The behavioral manifestations (epileptic score, latency, and number of seizures in 30min) and EEG changes were observed and recorded. Nissl staining and electrophysiological recording were used to assess neuronal damage and excitability in the hippocampal CA1 region, respectively. The levels of iron, glutathione (GSH), and malondialdehyde (MDA) in the hippocampus were assessed by spectrophotometry. Immunofluorescence staining was used to detect lipoxygenase 15 (15-LOX) expression. Western blot was used to determine glutathione peroxidase 4 (GPX4) and 15-LOX protein levels. Vitamin E treatment was associated with decreased epileptic grade, seizure latency, and number of seizures in the PTZ-kindled epileptic model. Vitamin E treatment also decreased 15-LOX expression, inhibited MDA and iron accumulation, and increased GPX4 and GSH expression. In conclusion, vitamin E can reduce neuronal ferroptosis and seizures by inhibiting 15-LOX expression.