基于ceRNA调控网络研究青蒿素调节Cuprizone小鼠小胶质细胞极化的分子机制

目前治疗多发性硬化症最有效的方法是抑制过度免疫反应促进髓鞘再生。从植物中寻找免疫调节药物是当前的研究热点。在Cuprizone脱髓鞘模型中，M1型小胶质细胞明显增加而M2型细胞因子浓度降低，小胶质细胞中lncRNA Gm4117的表达下调，而miR-764-3p和miR-297b-5p的表达上调。青蒿素处理两周后，脱髓鞘得到缓解并且上述基因改变出现明显逆转。预实验发现，小胶质细胞中miR-764-3p和miR-297b-5p分别靶向STAT3和STAT6，且lncRNA Gm4117存在miR-764-3p和miR-297b-5p的结合位点。本项目拟研究青蒿素是否通过ceRNA来促进STAT3/6的表达，从而使小胶质细胞向M2型极化并最终促进髓鞘再生修复。本研究将探索青蒿素在多发性硬化症中的应用及其药理学机制，具有重要的理论意义和临床价值。

Inhibiting excessive immune response is one of the most effective treatments for multiple sclerosis (MS). In the Cuprizone-induced demyelination model, the number of M1 microglia increased, while the concentration of M2 cytokines decreased. The expression of lncRNA Gm4117 in microglia was down-regulated while the expression of miR-764-3p and miR-297b-5p was upregulated. Two weeks of artemisinin treatment significantly reversed the myelin loss. Our preliminary results revealed that miR-764-3p and miR-297b-5p might target STAT3 and STAT6 in microglia, respectively. We also found potential binding sites of miR-764-3p and miR-297b-5p in lncRNA Gm4117. We aim to investigate whether artemisinin promotes microglia M2-type polarization through increasing STAT3/6 by ceRNA. It may shed light on pathological mechanism of MS and the application of artemisinin in clinical practice.