祛痰化瘀方剂调控巨噬细胞内氧化应激与促炎因子产生稳定易损斑块的机制

项目名称： 祛痰化瘀方剂调控巨噬细胞内氧化应激与促炎因子产生稳定易损斑块的机制

项目编号： No.81503504

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 高青

作者单位： 天津中医药大学

项目金额： 18万元

中文摘要： 炎症与氧化应激是动脉粥样硬化斑块易损的关键机制，斑块内巨噬细胞（Mф）是促炎因子与氧化应激的主要来源。近期研究发现氧化应激与促炎因子的产生受PKC/cPLA2/AA信号通路共同调控。花生四烯酸（AA）不仅是调控氧化应激关键酶--NADPH氧化酶活性的重要因素，其代谢产物又是炎性介质，可放大炎症反应，因此上述通路为重要的干预靶点。祛痰化瘀方可通过抑制炎症反应、抗氧化减缓动脉粥样硬化进程并稳定斑块，且前期工作显示祛痰化瘀方能下调Mф内AA的水平。据此我们提出假设：祛痰化瘀方可通过PKC/cPLA2/AA信号通路调控Mф氧化应激与促炎因子的产生达到稳定斑块的作用。本研究拟以祛痰化瘀方干预apoE-/- 小鼠动脉粥样硬化模型和Mф源性泡沫细胞模型，基于PKC/cPLA2/AA信号通路观察活性氧与促炎因子产生过程中相关物质的变化，揭示祛痰化瘀方稳定斑块作用的分子机制及具体靶点，为临床治疗另辟新径。

中文关键词： 易损斑块；巨噬细胞；氧化应激；炎症；祛痰化瘀方

英文摘要： Inflammation and oxidative stress are the crucial mechanism that involve in vulnerable plaques. Macrophages in plaques produce a large number of reactive oxygen species and proinflammatory factors. Recently research shows that the PKC/cPLA2/AA signaling pathway plays the key role in network control of oxidative stress and proinflammatory factor production. Arachidonic acid (AA) can induce the production of NADPH oxidase and, as an inflammatory medium, series of proinflammatory factor, thereby the mentioned pathway is an important intervention target. The reducing phlegm and removing dampness method can improve clinical symptoms in patients with atherosclerosis, inhibiting inflammatory reaction and stable plaques. Previous studies showed the reducing phlegm and removing dampness method can reduce AA production in macrophages. In this basis, we propose a hypothesis that the reducing phlegm and removing dampness method can regulate macrophage oxidative stress and proinflammatory factor production through the PKC/cPLA2/AA signaling pathways in order to achieve stable plaques. This research intends to use the reducing phlegm and removing dampness method intervention, on the basis of related animal and cell models, to analysis of the action mechanism of the reducing phlegm and removing dampness method in the process of reactive oxygen species and proinflammatory factor and the related material production from PKC/cPLA2/AA signaling pathways, in order to clarify the drug targets, provide new therapies for clinical treatment.

英文关键词： Vulnerable plaque;Macrophages;Oxidative Stress;Inflammation;Reducing phlegm and removing dampness method