LncRNA CCAT1/miR-101a/GAT-1介导蒙医温针治疗失眠的作用及机制研究

失眠已成为严重的公共健康问题。课题组证实，蒙医温针治疗失眠疗效显著，但机制不详。我们研究显示，长链非编码RNA(lncRNA)结肠癌相关转录因子1(CCAT1)调节微小RNA-101a (miR-101a)表达，但具体调控机制尚不清楚。在预实验中，我们发现：蒙医温针调节失眠大鼠脑组织miR-101a表达；γ-氨基丁酸转运体-1(GAT-1)是miR-101a的靶基因。资料表明，GAT-1调节GABA能突触传递变化，进而激活GABAA受体通路。因此，我们推测“蒙医温针治疗影响失眠大鼠脑组织lncRNA CCAT1/miR-101a表达，并经GAT-1参与调节GABA及GABAA受体通路” 是蒙医温针调节睡眠的新机制。本项目拟分析蒙医温针对失眠大鼠的治疗作用，并从动物-细胞-分子层次探讨其经lncRNA CCAT1/miR-101a/GAT-1调节睡眠的分子机制。此研究将为失眠防治提供新思路。

Insomnia has become a serious public health problem. Our group has confirmed that Mongolian medical warm acupuncture has significant curative effect in treating insomnia in rats, but the underlying mechanisms remain poorly understood. Our research showed that long noncoding RNA (lncRNA) colon cancer associated transcript-1 (CCAT1) regulated the expression of miR-101a. However, the regulation mechanism remains largely unknown. In a preliminary experiment we further found that Mongolian medical warm acupuncture regulated the expression of miR-101a in the brain of model of insomnia in rats. Additionally, γ-aminobutyric acid transporter 1 (GAT-1) is one of the target genes of miR-101a. It has been reported that GAT-1 regulated GABAergic synaptic transmission. The previous study also found that GABAergic synaptic transmission activated GABAA receptor. Therefore, we suppose that Mongolian medical warm acupuncture influenced the level of lncRNA CCAT1/mir-101a axis in the brain of model of insomnia in rats, which were capable of activating GABAA receptor signaling through GAT-1 and GABA and contribute to sleep regulation. The aim of this study is to analyze the therapeutic effect of Mongolian medical warm acupuncture on insomnia in rats. Also, its possible mechanism will be investigated based on lncRNA CCAT1/miR-101a/GAT-1 axis at whole body, cellular and molecular levels. This work has the potential to bring new ideas for the successful prevention and treatment of insomnia.