NLRP3/ASC/Caspase-1信号通路在大气细颗粒物促发动脉粥样硬化中的作用机制

项目名称： NLRP3/ASC/Caspase-1信号通路在大气细颗粒物促发动脉粥样硬化中的作用机制

项目编号： No.91543119

项目类型： 重大研究计划

立项/批准年度： 2016

项目学科： 化学工业

项目作者： 赵金镯

作者单位： 复旦大学

项目金额： 75万元

中文摘要： 大气细颗粒物（fine particle，PM2.5）及其组分对心肺系统的影响受到广泛的关注，其中PM2.5对动脉粥样硬化（atherosclerosis，AS）发生发展的影响多年来在流行病学研究中得到了广泛地论证，但其生物学机制尚不清楚。大气PM2.5复杂的来源及组成成分特征在城市空气污染中尤为重要。本项目主要关注不同天气状态下及不同来源区域PM2.5的浓度及组成成分。同时，以ApoE-/-小鼠建立AS动物模型，采用PM2.5吸入暴露装置使小鼠长期暴露于PM2.5，观察PM2.5对AS发展的影响，结合体外细胞实验，围绕免疫反应和炎症反应，探索NLRP3炎症小体信号通路（NLRP3/ASC/caspase-1/IL-1β，IL-18）调节机制在PM2.5及其组成成分促发AS发展中的作用。本研究可能为保护人群健康及探寻与PM2.5相关的AS预防和干预靶点提供科学依据。

中文关键词： 细颗粒物；动脉粥样硬化；NLRP3炎症小体；作用机制

英文摘要： The effects of fine particle (PM2.5) on cardiopulmonary system have been widely concerned in recent years. It has been fully certified the effects of PM2.5 on atherosclerosis in epidemiological studies. However, the biological mechanism is not clear yet. The complicated sources and components of ambient PM2.5 are very important in air pollution in big city. The current study mainly focuses on the concentration and components of PM2.5 in different wheather conditions and different areas. Meanwhile, the Apoe-/- mice are used to establish the atherosclerosis model. The “Air Pollution Exposure System” is used to give the mice concentrated PM2.5 exposure to observe the effects of PM2.5 on the development of atherosclerosis. Combining the animal experiment with the vitro experiment, the study focuses on the immune and inflammatory response to explore regulatory mechanism of NLRP3-related signaling pathway (NLRP3/ASC/caspase-1/IL-1β, IL-18) in PM2.5-induced atherosclerosis. This project will provide scientific basis for protecting people’s health and finding the preventive and intervention target for PM2.5-induced atherosclerosis.

英文关键词： fine particles;atherosclerosis;NLRP3 inflammasome;mechanism