Long non-coding RNA H19 alleviates hippocampal damage in convulsive status epilepticus rats through the nuclear factor-kappaB signaling pathway

Previous studies have demonstrated that inflammation plays a critical role in hippocampcal damage and cognitive dysfunction induced by convulsive status epilepticus (CSE). Emerging evidence indicated that the long non-coding RNA (lncRNA) H19 acts as an important regulator of inflammation in various diseases. However, the role of H19 in CSE is still unkonwn. In the present study, pilocarpine-induced SE rat model was used to explore the role of H19 in hippocampal neuron damage in CSE. Our results indicated that the increased level of H19 is positively correlated with the expression of inflammatory cytokines (TNF-α and IL-1β) in hippocampus of SE rats. Moreover, knockdown of H19 could inhibit the activation of microglia and suppress the expression of inflammatory cytokines via nuclear factor-kappaB (NF-κB) signaling pathway. It was further revealed that downregulation of H19 could alleviate hippocampal neuron damage induced by CSE. These findings indicated that H19 modulates inflammatory response and hippocampal damage through the NF-κB signaling pathway in the CSE rats, which provides a promising target to alleviate hippocampcal damage of CSE.既往研究已证实，炎症在惊厥性癫痫持续状态（convulsive status epilepticus, CSE）诱导的海马损伤及认知功能障碍中发挥关键作用。越来越多的证据表明，长链非编码RNA（long non-coding RNA, lncRNA）H19可作为多种疾病中炎症反应的重要调控因子。然而，H19在CSE中的作用仍未明确。本研究采用毛果芸香碱诱导的癫痫持续状态大鼠模型，探究H19在CSE所致海马神经元损伤中的作用。结果显示，H19表达上调与癫痫持续状态大鼠海马组织内炎症因子（肿瘤坏死因子-α，TNF-α；白细胞介素-1β，IL-1β）的表达呈正相关。此外，敲低H19可通过核因子κB（nuclear factor-kappaB, NF-κB）信号通路抑制小胶质细胞活化，并下调炎症因子的表达。进一步研究发现，H19下调可减轻CSE诱导的海马神经元损伤。上述结果表明，在CSE大鼠中，H19通过NF-κB信号通路调控炎症反应与海马损伤，为缓解CSE所致的海马损伤提供了极具前景的治疗靶点。