抑制血管内皮炎症反应是防治动脉粥样硬化（AS）等心血管疾病的重要策略。前期发现天然来源卤酚类活性衍生物能显著抑制人脐静脉内皮细胞（HUVECs）炎症反应，其作用可能是通过丝裂原活化蛋白激酶（MAPK）信号通路来调节的，但具体机制还不清楚。本课题以高活性新化合物LM49为探针，应用化学生物学方法，探讨其对脂多糖（LPS）诱导的血管内皮炎症MAPK信号通路的调控作用；通过蛋白质组学研究LM49抑制血管内皮炎症反应前后蛋白质谱的改变，经图像分析后选取差异蛋白斑点进行MALDI-TOF-MS/MS 鉴定目标蛋白，寻找相关的新信号调节靶蛋白，利用RNA干扰/过表达方法进行反向验证，采用同源模建/分子对接（Docking）等计算机辅助技术识别生物靶点，从分子-细胞-整体动物三个层次综合分析探讨该类小分子对调控LPS诱导的血管内皮炎症MAPK信号通路的作用及机制，为其结构优化提供科学依据。

Inhibiting vascular endothelium inflammation is an effective strategy for the treatment of atherosclerosis (AS) and other associated cardiovascular diseases. Severl natural new halophenol derivatives prepared by our group showed strong inhibitory activities on the inflammation of human umbilical vein endothelial cells(HUVECs) and could regulate the action via mitogen activited protein kinase(MAPK) signal pathway. However,the action mechanism is unclear. In the present study, a strong active derivative LM49 is selected as a small molecule probe to investigate its regulatory mechanism on the LPS-induced MAPK signal pathway in vascular endothelium by chemical and cell biology methods. By the proteomics technique, the changed proteins can be founded after treatment with LM49 in the vascular endothelium inflammation. The differential proteins will be investigated through analyzing the protein profiles and identified by MALDI-TOF-MS/MS to find the related target proteins, which will be further verified by RNA interference/overexpression methods. The biological targets can also be recognized by a computer-assisted homology modeling/molecular docking technique. The regulatory mechanism of such small molecule compound as LM49 on the LPS-induced MAPK signal pathway will be compositely analyzed and investigated from molecule-cell-whole animal levels to provide the scientific basis for the further structural optimization of halophenol compounds.