Pharmaco-resistance is a challenging problem for treatment of status epilepticus (SE) in the clinic. P-glycoprotein (P-gp) is one of the most important multi-drug transporters that contribute to drug resistance of SE. Long noncoding RNAs (lncRNAs) have been increasingly recognized as versatile regulators of P-gp in tumors and epilepsy. However, the function of lncRNAs in drug resistance of SE remains largely unknown. In the present study, pilocarpine-induced rat model is used to explore the expression profiles of lncRNAs in the hippocampus of SE using RNA sequencing. Our results implied that the level of lncRNA H19 was significantly increased in the hippocampus of SE rats, which was positively correlated with the level of P-gp. While downregulation of H19 could inhibit the expression of P-gp and alleviate neural damage in the hippocampus of SE rats. Furthermore, it was revealed that H19 regulates P-gp expression through the nuclear factor-kappaB (NF-κB) signaling pathway by functioning as a competing endogenous RNA against microRNA-29a-3p. Overall, our study indicated that H19 regulates P-gp expression and neural damage induced by SE through the NF-κB signaling pathway, which provides a promising target to overcome drug resistance and alleviate brain damage for SE.

药物耐药性是临床治疗癫痫持续状态（SE）的一个具有挑战性的问题。P-糖蛋白 (P-gp) 是导致 SE 耐药的最重要的多药转运蛋白之一。长链非编码 RNA (lncRNA) 越来越多地被认为是肿瘤和癫痫中 P-gp 的多功能调节剂。然而，lncRNA 在 SE 耐药性中的作用在很大程度上仍然未知。在本研究中，毛果芸香碱诱导的大鼠模型用于通过 RNA 测序探索 SE 海马中 lncRNA 的表达谱。我们的结果表明，SE 大鼠海马中 lncRNA H19 水平显着升高，与 P-gp 水平呈正相关。而下调H19可抑制P-gp的表达，减轻SE大鼠海马神经损伤。此外，据透露，H19 通过核因子-kappaB (NF-κB) 信号通路调节 P-gp 表达，作为与 microRNA-29a-3p 竞争的内源性 RNA。总的来说，我们的研究表明 H19 通过 NF-κB 信号通路调节 SE 诱导的 P-gp 表达和神经损伤，这为克服耐药性和减轻 SE 的脑损伤提供了一个有希望的目标。