长链非编码RNA XLOC_002473在实验性自身免疫性神经炎的作用机制研究

Long non-coding RNAs (lncRNAs) play a critical role in various physiological or pathological processes. The abnormal expression of lncRNA may lead to a various of human diseases. However, the effects of lncRNA on autoimmune disease of nervous system are still unknown. From microarray analysis, our previous study found that there were 273 up-regulated lncRNAs and 206 down-regulated lncRNAs in GBS patients compared with healthy controls. LncRNA XLOC_002473 was up-regulated four folds confirmed by RT-PCR. Moreover, we also found that the expression of lncRNA XLOC_002473 was up-regulated 5.6 folds in EAN rats. Using lncRNA XLOC_002473 inhibitor could decrease the severity of the clinical course. However, the mechanism of lncRNA XLOC_002473 on EAN rats remains unknown. The major aim: 1) explore the effects of lncRNA XLOC_002473 on EAN rats by assessment of histological and electrophysiological measures; 2) investigate its role in peripheral lymph nodes and spleen; 3) investigate the potential mechanisms of lncRNA XLOC_00247 in EAN rats. Our present study may provide basic information for using lncRNA XLOC_002473 for GBS diagnosis or target treatment in the future.

长链非编码RNA(lncRNA)参与细胞内多种生理病理过程，其表达或功能异常与许多人类疾病密切相关,但其对神经系统自身免疫性疾病的影响目前尚不明确。我们前期实验通过lncRNA芯片发现GBS患者外周血单核细胞中273个lncRNA表达上调、206个lncRNA表达下调，定量PCR证实lncRNA XLOC_002473表达上调了4倍。随后动物实验也证实该lncRNA在EAN大鼠中表达上调了5.6倍，而且lncRNA XLOC_002473抑制剂改善了EAN大鼠的临床症状，但其对EAN大鼠炎症反应的调控机制尚未明确。主要预期目标：1）分析lncRNA XLOC_002473对EAN大鼠神经电生理、炎症反应及周围神经脱髓鞘的影响；2）阐明其对外周免疫炎症反应的调节作用；3）揭示其对EAN大鼠炎症反应的调控机制。此研究将为lncRNA XLOC_002473作为GBS诊断、治疗的靶点奠定依据。