天然小分子化合物Lawsone在多发性硬化症中的作用及机制探究

我们最新研究发现凤仙花叶子中提取的天然小分子化合物Lawsone可显著缓解多发性硬化症（Multiple sclerosis，MS）动物模型小鼠EAE临床症状，而且体外和体内均显著性抑制炎性CD4+T细胞比例。但目前对于Lawsone如何缓解小鼠EAE临床症状，以及降低炎性CD4+T细胞比例的机制尚不清楚。基于此，我们提出Lawsone通过调控靶基因功能抑制炎性CD4+T细胞比例进而缓解MS发病的工作假说。因此，本课题将研究以下三个科学问题:（1）明确Lawsone对EAE的治疗作用;（2）分析Lawsone缓解EAE发病的效应免疫细胞类型;（3）探究介导Lawsone发挥作用的分子机制。本项目将揭示天然小分子化合物Lawsone调控MS的免疫机理，为MS的基础研究和临床治疗提供新的治疗靶点和理论依据。

Recently, we found that natural compound Lawsone which presents in the leaves of the henna plant (Lawsonia inermis) was efficacious EAE，a widely used mouse model of MS and a remarkable lower percentage of inflammatory CD4+ T cell was observed in vitro and in vivo. So far, how Lawsone ameliorates MS pathogenesis and mechanisms for reducing inflammatory CD4+ T cell remain unclear. Therefore, we hypothesize that Lawsone could inhibit inflammatory CD4+ T cell percentage by regulating the function of target genes to alleviate the pathogenesis of MS. Taken together, the following three scientific issues will be studied: (1) Clarify the therapeutic effect of Lawsone on EAE; (2) Analyze the types of effector cells that alleviate EAE pathogenesis; (3) Explore the molecular mechanisms of Lawsone on specific immune effector cells. This study will provide new immune insights of the small-molecular compound Lawsone regulated immune pathogenesis of MS and suggest possible drug targets and clues for the basic research and clinical treatment of MS.