摘要
癫痫是一种高发病率的慢性神经退行性疾病,影响所有年龄组。难治性癫痫(RE)发生在约30-40%的癫痫猝死(SUDEP)高危病例中。最近的研究表明,癫痫自发性发作可能与氧化应激和活性氧衍生物(ROS)产生的增加有关。ROS浓度增加导致脂质过氧化、蛋白质氧化、核遗传物质破坏、酶抑制和细胞死亡,其机制被称为“铁死亡”(Fts)。谷胱甘肽过氧化物酶4 (GPX4)失活可诱发Fts,而氧化应激与细胞内游离铁(Fe+2)浓度升高有关。Fts也是一种非凋亡性程序性细胞死亡机制,其中缺氧诱导因子1α (HIF-1α)依赖的缺氧应激样状态似乎随着铁和细胞毒性ROS在受影响细胞中的积累而发生。假设惊厥危象为缺氧应激,重复惊厥/缺氧应激可能是“癫痫性心脏”(EH)的有效诱导剂,其特征是自主神经功能改变和恶性或致命性心动过缓的高风险。我们之前报道了实验性复发性癫痫发作诱导与SUDEP相关的心肌细胞Fts。此外,最近在急性心肌梗死中发现了几个与Fts和缺氧相关的基因。最近研究的一个新主题表明,通过调节xCT反转运系统(SLC7A11)的表达或活性来抑制GPX4,可以控制细胞对铁凋亡引起的氧化应激的敏感性。此外,在缺氧时,应激转录因子ATF3的表达增加可以以hif -1α依赖的方式促进erastin诱导的Fts。我们认为,ROS清除剂、铁螯合剂、抗氧化剂和转氨酶抑制剂抑制Fts可能对癫痫有治疗作用,并通过保护心脏免受铁上睑衰竭而改善SUDEP的预后。
关键词: 难治性癫痫,SUDEP, p -糖蛋白,铁下垂,SLC7A11,癫痫性心脏。
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