NLRP3炎症小体在大气细颗粒物促发2型糖尿病中的作用机制

大气细颗粒物（PM2.5）对除心、肺系统疾病之外的2型糖尿病（Type 2 diabetes mellitus, T2DM）的影响近年来受到广泛的关注，但其生物学机制尚不清楚。同时，大气PM2.5复杂的来源及组成成分特征在城市空气污染及健康危害中的作用也有待进一步阐明。本项目采用固定群组研究观察大气个体PM2.5暴露水平及其组成成分与T2DM发展的关系，建立暴露-效应模型，同时以KKAy小鼠建立T2DM动物模型，采用PM2.5动态吸入暴露装置观察PM2.5长期暴露对T2DM发展的影响。研究结合人群流行病学和动物实验研究，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T2DM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T2DM预防和干预靶点提供科学依据。

The effects of fine particle (PM2.5) on extra-cardiopulmonary diseases such as type 2 diabetes mellitus (T2DM) have been widely concerned in recent years. However, the biological mechanism is unclear yet. The effects of complicated sources and components of ambient PM2.5 on health need to be elucidated. The current study uses panel study to obsever the association between PM2.5 and its consitituents and the development of T2DM, and establish the exposure-response model. Meanwhile, the KKay mice are used to establish the T2DM 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 T2DM. Combining the epidemiological study with animal experiment, the project focuses on the immune and inflammatory response to explore the regulatory mechanism of NLRP3-related signaling pathway (NLRP3/ASC/caspase-1/IL-1β, IL-18) in PM2.5-induced T2DM. This project will provide scientific basis for protecting people’s health and finding the preventive and intervention target for PM2.5-induced T2DM.