Although many advances have been made in the pathogenesis of epilepsy recently, the pathological mechanisms of epilepsy are still largely unknown. Exploring the pathological mechanisms and developing novel therapeutic strategies for epilepsy are urgently needed. A SD rat model of epilepsy was established with lithium chloride-pilocarpine. Astrocytes were isolated, cultured from 8 to 12 week rats and identified by flow cytometry and immunofluorescence. Immunohistochemical staining was used for MEF2C and NF-κB in paraffin-embedded sections. RT-qPCR and western blot were used to analyze gene expression. ELISA was used to analyze the concentration of IL-6, TNF-α and Cox-2. Cells were transfected with pcDNA-MEFC2, sh-MEFC2, pcDNA-UCA1, sh-UCA1, miR-203 mimic or miR-203 inhibitor. Cell viability was assessed by MTT assay. Dual luciferase assay was used to determine the direct interaction of lncRNA UCA1/miR-203 and miR-203/MEF2C. MEF2C was down-regulated and inhibited NF-κB expression and the secretion of IL-6 and TNF-α in epilepsy. LncRNA UCA1 was also down-regulated in epilepsy. LncRNA UCA1 over-expression increased the expression of MEF2C and its knock-down decreased MEF2C expression. Luciferase activity showed lncRNA UCA1 directly targeted miR-203 and miR-203 directly targeted MEF2C. MiR-203 suppressed the expression of MEF2C, and promoted NF-κB, phosphorylated IκB/IKK and inflammatory effectors, which was reversed by MEF2C knock-down. Moreover, lncRNA UCA1 could increase the expression of MEF2C to inhibit NF-κB, phosphorylated IκB/IKK and inflammatory effectors, which was also reversed by miR-203 mimic transfection. LncRNA UCA1 inhibited the inflammation via regulating miR-203 mediated regulation of MEF2C/NF-κB signaling in epilepsy. Our investigation elucidated novel pathological mechanisms and provided potential therapeutic targets for epilepsy.

中文翻译：

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LncRNA UCA1通过调节miR-203介导的癫痫MEF2C /NF-κB信号通路的调节来抑制炎症。

尽管最近在癫痫的发病机理方面已经取得了许多进展，但是癫痫的病理机制仍是很大程度上未知的。迫切需要探索癫痫的病理机制和开发新的治疗策略。用氯化锂-毛果芸香碱建立癫痫的SD大鼠模型。分离星形胶质细胞，在8至12周的大鼠中培养，并通过流式细胞术和免疫荧光鉴定。免疫组织化学染色用于石蜡包埋切片中的MEF2C和NF-κB。用RT-qPCR和western blot分析基因表达。ELISA用于分析IL-6，TNF-α和Cox-2的浓度。用pcDNA-MEFC2，sh-MEFC2，pcDNA-UCA1，sh-UCA1，miR-203模拟物或miR-203抑制剂转染细胞。通过MTT测定评估细胞活力。使用双重荧光素酶测定法来确定lncRNA UCA1 / miR-203和miR-203 / MEF2C的直接相互作用。MEF2C被下调并抑制了癫痫中NF-κB的表达以及IL-6和TNF-α的分泌。LncRNA UCA1在癫痫中也被下调。LncRNA UCA1过表达增加了MEF2C的表达，其敲低降低了MEF2C的表达。萤光素酶活性显示lncRNA UCA1直接靶向miR-203和miR-203直接靶向MEF2C。MiR-203抑制了MEF2C的表达，并促进了NF-κB，磷酸化的IκB/ IKK和炎性效应因子，而MEF2C的抑制作用则逆转了这一现象。此外，lncRNA UCA1可以增加MEF2C的表达，从而抑制NF-κB，磷酸化的IκB/ IKK和炎症效应，而miR-203模拟转染也可以逆转这种现象。LncRNA UCA1通过调节miR-203介导的癫痫MEF2C /NF-κB信号传导的调节来抑制炎症。我们的研究阐明了新型的病理机制，并为癫痫症提供了潜在的治疗靶标。