空气颗粒物暴露致肺部和骨关节炎性反应的作用机理

项目名称： 空气颗粒物暴露致肺部和骨关节炎性反应的作用机理

项目编号： No.91543124

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： 刘亚军

作者单位： 北京积水潭医院

项目金额： 78万元

中文摘要： 空气颗粒物暴露致呼吸和心血管等系统健康危害已有诸多研究，然而其诱发其它组织器官损伤(如远端骨关节）的研究却较少，对机制的探究几乎为零。我们初步的流行病学调查显示：颗粒物暴露与骨关节炎症发生之间存在一定的相关性；实验研究表明，碳纳米颗粒物暴露可诱发小鼠肺部、骨关节及系统性炎症反应。然而，目前仍有诸多亟待解决的科学问题：⑴空气颗粒物暴露与肺部炎症及骨关节疾病发生或恶化的相关性？⑵空气颗粒物继发或加剧骨关节炎性反应的作用途径：是直接还是间接效应（如通过呼吸系统炎性反应继发）？其主要信号通路是什么？针对这些问题，本项目一方面将扩大样本量开展流行病学调查，明确颗粒物与肺部炎症反应和骨关节疾病的相关性。另一方面，制备黑碳样品及其与重金属或有机污染物复合体，通过建立动物暴露模型阐明颗粒物的组织分布和诱发肺部与骨关节炎性反应的毒性特征，进一步通过细胞研究揭示其导致肺部和骨关节炎性反应的作用途径和分子机制。

中文关键词： 环境毒理；空气颗粒物；黑碳；肺部炎症；骨性关节炎

英文摘要： Most studies have focused on the direct health effects upon air particulate matter exposure, such as respiratory and cardiovascular diseases. However, little attention has been paid to other organs including bone joints, with little insight into the corresponding mechanisms. Our previous study recognized a correlation between the exposure of air pollution and the occurrence of bone joint inflammation in patients. Meanwhile, animal experiments also indicated that carbon materials can induce local (including lung and bone joints) and systematic inflammation. Together, previous studies suggested that inflammation in bone joints may be greatly attributed to air particulate matter exposure. However, many questions remain unanswered thus far. First, is there an association between air particulate matter exposure and bone joint diseases? Second, what’s the underlying mechanism responsible for bone joint diseases under air pollution? To be specific, is the damage to bone joints directly or indirectly linked to exposure of air pollution? In other words, what is the contribution of lung inflammation to joint diseases under air pollution? To address these questions, on one hand, we will conduct in-depth epidemiological study by enlarging our sample size to confirm the relationship between air particulate matter exposure and the occurrence of lung inflammation and bone joint diseases. On the other hand, black carbon particles and the complexes of black carbon with heavy metals or organic pollutants will be made. Thereafter, their tissue distribution and toxicological features related to inflammation in lung and bone joints will be thoroughly investigated. Furthermore, great efforts will be made to illustrate the underlying molecular mechanisms for lung and joint inflammation upon exposure to black carbon particles and black carbon complexes.

英文关键词： Environmental toxicology;Air particulate matter;Black carbon;Lung inflammation;Osteoarthritis