孕期二氧化氮（NO2）吸入暴露诱导子代支气管哮喘易感性变化及其分子机制

项目名称： 孕期二氧化氮（NO2）吸入暴露诱导子代支气管哮喘易感性变化及其分子机制

项目编号： No.21477070

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 化学工业

项目作者： 李广科

作者单位： 山西大学

项目金额： 86万元

中文摘要： 二氧化氮(NO2)吸入暴露可增加人群支气管哮喘患病风险。而近期研究提示，生命早期特别是孕期接触污染物可能是哮喘发病率增加的一个重要原因。目前对NO2呼吸系统毒性特征和健康效应的研究主要集中在儿童或成年本体，忽略了母体尤其是孕期暴露对子代哮喘易感性的影响。为此，本项目拟开展以下工作：（1）研究孕期NO2暴露对胚胎生存率、胎儿出生后生长和肺功能发育的影响。（2）在解析内暴露机制的基础上，明确母体孕期暴露对子鼠气道炎症和气道高反应性的影响；进而通过对子鼠分别进行过敏原激发和过敏原致敏+激发（哮喘模型）处理，结合芯片筛查阐明子代哮喘易感性增加的效应及发病机理。（3）分析孕期NO2暴露对子代气管和肺Th1/Th2分化失衡标志因子表达的影响，结合特异性阻断技术确定Th2优势应答及在此过程中JAK/STAT6 信号调控机制。旨在为建立NO2污染危险度评价指标、揭示人体暴露健康效应提供科学依据和技术支持。

中文关键词： 孕期暴露；二氧化氮（NO2）；子代；支气管哮喘易感性；分子机制

英文摘要： Nitrogen dioxide (NO2) inhalation exposure increases the morbidity and mortality risk of bronchial asthma. Recent studies imply that exposure to environmental pollutants during early life, especially pregnancy, is responsible for the dramatic increase in asthma incidence. However, existing evidenve for the toxic characteristics of respiratory system and its health effects from NO2 exposure mainly focused on child and/or adult, rarely touching whether maternal pregnancy exposure affect the asthma susceptibility in the offsprings. For this reason, in the present study (1) we will confirm the effects of maternal exposure to NO2 during pregnancy on the ratio of embryonic survival, the growth of fetus after birth and lung function development. (2) we will probe the internal exposure mechanisms, and determine the airway inflammation and airway hyperresponsiveness of offsprings after maternal exposure during the pregnancy; furthermore,using affymetrix genome arrays, we will clarify the increased susceptibility of asthma and its pathogenesis by treating the fetus with allergen provacation and traditional asthma model,respectively.(3) we will analyze the differentiation factors expression of Th1/Th2 imbalance on the trachea and lung in offsprings after exposure to NO2 during pregnancy, and detect JAK/STAT6 signal mechanism in Th2-type responses by applying specific interfering techniques. This work is undertaken to provide a scientific basis and technical support for setting up risk assessment indicators, and revealing the human health effects resulting from NO2 exposure in atmospheric polluting area.

英文关键词： Pregnant exposure;Nitrogen dioxide (NO2);Offspring;Bronchial asthma susceptibility;Molecular mechanism