Epilepsy is a common neurological disease. The dysregulated long noncoding RNAs (lncRNAs) are implicated in epileptogenesis. The aim of this research is to explore the role and mechanism of lncRNA zinc finger antisense 1 (ZFAS1) in status epilepticus (SE)-induced hippocampal neurons injury. SE mice model was established and primary hippocampal neurons were isolated. The expression levels of ZFAS1 and microRNA-421 (miR-421) were detected in hippocampus and hippocampal neurons via quantitative reverse transcription polymerase chain reaction. Hippocampal neurons viability, apoptosis and autophagy were analyzed via Cell Counting Kit-8, flow cytometry and western blot. The target relationship between ZFAS1 and miR-421 was analyzed via dual-luciferase reporter assay. The phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) pathway was blocked by LY294002 and related protein levels were detected via western blot. ZFAS1 expression was elevated in hippocampus and hippocampal neurons from SE mice. Knockdown of ZFAS1 increased SE hippocampal neurons viability and decreased apoptosis and autophagy. ZFAS1 could sponge miR-421. MiR-421 expression was declined in SE mice tissues and cells. Down-regulation of miR-421 abolished the suppressive effect of ZFAS1 knockdown on hippocampal neurons apoptosis and autophagy. Silencing of ZFAS1 induced activation of the PI3K/AKT pathway by up-regulating miR-421. Inhibition of the PI3K/AKT pathway reversed the effect of ZFAS1 knockdown on SE hippocampal neurons apoptosis and autophagy. Interference of ZFAS1 attenuated hippocampal neurons apoptosis and autophagy in SE by increasing miR-421 and activating the PI3K/AKT pathway, indicating a new mechanism for understanding the pathogenesis of SE.

癫痫病是一种常见的神经系统疾病。失调的长非编码RNA（lncRNA）参与癫痫发生。本研究的目的是探讨lncRNA锌指反义1（ZFAS1）在癫痫持续状态（SE）引起的海马神经元损伤中的作用和机制。建立SE小鼠模型并分离原代海马神经元。通过定量逆转录聚合酶链反应检测海马和海马神经元中ZFAS1和microRNA-421（miR-421）的表达水平。通过Cell Counting Kit-8，流式细胞仪和western blot分析海马神经元的活力，凋亡和自噬。ZFAS1和miR-421之间的靶标关系通过双荧光素酶报告基因分析进行了分析。LY294002阻断了磷酸肌醇3激酶（PI3K）/蛋白激酶B（AKT）通路，并通过蛋白质印迹检测了相关蛋白水平。在SE小鼠的海马和海马神经元中ZFAS1表达升高。敲低ZFAS1可增加SE海马神经元的活力，并减少细胞凋亡和自噬。ZFAS1可以海绵miR-421。在SE小鼠组织和细胞中，MiR-421表达下降。miR-421的下调消除了ZFAS1敲低对海马神经元凋亡和自噬的抑制作用。ZFAS1沉默可通过上调miR-421诱导PI3K / AKT途径的激活。PI3K / AKT途径的抑制逆转了ZFAS1敲低对SE海马神经元凋亡和自噬的影响。