PM2.5和甲醛复合暴露致小鼠哮喘样病变分子机制的研究

PM2.5 and formaldehyde are two kinds of air pollutants with serious harmful effects to human health. PM2.5 exists in outdoor environment and formaldehyde exists in indoor environment, and their combined exposure is very serious. Epidemiological studies show that they both can induce and worsen allergic asthma, but currently we do not know whether they have synergistic effects of their combined exposure, and what are the molecular mechanisms of these synergistic toxicological effects. The project intends to carry out the research at three levels, namely: in vitro studies, in vivo animal studies and a panel study. The main objectives of this project are: to construct human asthma-like mouse models induced by PM 2.5 along or combined exposure with formaldehyde, and to explore the forming molecular mechanisms of their asthmatic mouse models. Our group has successfully pre-constructed animal models of allergic asthma induced by inhaled formaldehyde and intratracheal perfused nanomaterials (particulate matter), and has made some progress on the environmental pollutants induced allergic asthma mechanisms. Some of our research papers have been published in the International SCI Journals. We have not only accumulated some experience in the preparation of environmental pollutant-induced animal asthma models, but also obtained some breakthroughs in the basic scientific hypothesis and theory on this field. Therefore our group already has had the infrastructure and capacity for undertaking the project.

PM2.5和甲醛是两种严重危害人类健康的空气污染物，一种存在于室外，一种存在于室内，而且复合污染情况较为严重。流行病学表明它们都可以诱导和恶化过敏性哮喘，但是目前並不知道它们的复合污染是否具有协同作用，以及协同毒理作用的分子机制。本项目研究拟从三个层面展开研究，即：体外细胞水平的研究，动物体内整体水平的研究和人群定组研究。项目研究的目标是：构建PM2.5单独暴露和与甲醛复合暴露的人类哮喘小鼠模型，并利用所构建的动物模型探讨PM2.5单独暴露和与甲醛复合暴露诱导过敏性哮喘的分子机制。本研究组前期已成功制备了甲醛吸入和纳米材料（颗粒物）气管滴注诱导的过敏性哮喘动物模型，在环境污染物诱导过敏性哮喘的机制研究上也有一定的进展。多篇学术论文已经在国际SCI杂志上发表，不但在制备环境污染物诱导性哮喘动物模型方面积累了一定的经验，而且在科学假说和基础理论上也有一定的突破，故具备完成本项目的基础和能力。

本国家自然科学基金面上项目：PM2.5和甲醛复合暴露致小鼠哮喘样病变分子机制的研究（21577045），经过课题组4年的努力，圆满完成任务：(1)已经成功构建PM2.5和/或甲醛暴露诱导的型人类哮喘小鼠模型，所构建的哮喘动物模型被广泛引用；通过研究已经证实了我们的科学假说：PM2.5和甲醛的暴露可活化氧化应激通路,进一步活化TRPV1和TSLP通路,最后活化I型超敏反应通路，诱导哮喘发作；通过我们的研究首先发现有关的生物标志物包括：TRPV1和T-IgE。(2)发表学术论文24篇，其中英语SCI论文23篇，中文核心期刊论文1篇；第一标注本项目编号论文13篇，第二标注本项目编号论文11篇；(3)培养博士研究生5名，硕士研究生11名。(4)积极开展了国际学术交流：4名博士研究生出国联合培养总计5年，邀请国外教授来访 3人次。