毛蕊异黄酮激活Egr-1信号途径促Treg极化治疗多发性硬化症的作用机制研究

多发性硬化症（MS）是一种免疫介导的中枢神经系统炎症性脱髓鞘疾病，目前仍无药可根治。我们前期发现Egr-1通过直接结合Foxp3启动子区域并促进其表达，促CD4+T细胞向Treg极化，继而抑制神经炎症反应，在MS/EAE发病进程中发挥重要作用，可作为治疗MS药物的有效靶点；而预实验结果表明毛蕊异黄酮（CAL）能显著激活Egr-1转录活性，促Treg细胞极化，缓解MS模型小鼠EAE的疾病进程。综上，我们提出假说：CAL通过激活Egr-1信号途径，促CD4+T细胞向Treg极化，继而抑制神经炎症反应，治疗MS/EAE。我们将在CD4+T细胞条件性敲除Egr-1小鼠、ERE-EGFP转基因小鼠、原代培养的CD4+T细胞和小胶质细胞系中，采用神经免疫学、细胞生物学和分子生物学等技术手段验证此假说，为临床治疗MS的新药研发提供新的思路，为传统中药黄芪及其活性成分成分应用于临床奠定理论基础。

Multiple sclerosis (MS) is a demyelinating autoimmune disease that occurs in the central nervous system (CNS), and there is still no medicine to cure. We found that Egr-1 could directly bind to the Foxp3 promoter region and accelerate its expression to induce the differentiation of CD4+ T cells into Treg subtype , which inhibits neuroinflammatory response and plays an important role in the pathogenesis of MS. Therefore, the Egr-1 signaling pathway could be used as an effective target for MS treatment, drug research and development. Our preliminary data have shown that calycosin (CAL) significantly activated Egr-1 signaling pathway to prompt the polarization of Treg cells and suppressed neuroinflammatory response, thereby reduced the nerve damage of MS/EAE. So, we put forward the hypothesis: CAL promotes the polarization of CD4+ T cells to Treg subtype by activating the Egr-1 signaling pathway, which can suppress neuroinflammatory response and be used to treat MS. Neuroimmunological, molecular biology and other related technologies will be used to confirm the hypothesis, which may provide a novel idea for the development of new drugs for clinical treatment of MS, and form a theoretical foundation for the clinical application of traditional chinese medicine Astragalus and its active ingredients.