PM2.5对哮喘发病影响及其机制研究

The incidence of asthma in China has an obvious increasing trend in recent 20 years. The effect of air pollution especially PM2.5 on the incidence of asthma has been focused by public. The epidemiologic studies show that the exposure to PM2.5 is significantly associated to exacerbations of asthma. However, the exactly relationship between PM2.5 and the formation of asthma remains unclear. We will collect PM2.5 from Beijing urban area to explore the effect of PM2.5 on the formation of asthma by an animal model. By now, the effect of PM2.5 on immune system and the mechanisms of PM2.5 promoting formation of asthma need further study. It has been reported that the regulatory T cells and thymic stromal lymphopoietin play an important role in asthma. By now, there aren’t further studies about the effect of PM2.5 on the regulatory T cells and thymic stromal lymphopoietin. We will research about the effect of PM2.5 on the balance of Th1/Th2 and the expression of Toll-like receptor, the effect on the quantity and function of the regulatory T cells and the effect on the expression of thymic stromal lymphopoietin. We will explore the possible immune mechanisms that PM2.5 promotes the formation of asthma. We will provide laboratory data to prevent asthma and set reasonable control measures on air pollution.

近20年，中国哮喘的发病率呈现明显上升趋势。大气污染特别是PM2.5对哮喘发病的影响成为公众关注的热点。流行病学调查显示PM2.5的暴露与哮喘加重有明显相关性，但与哮喘发病的关系尚不明确。本课题将采集北京城区PM2.5，通过动物模型检验PM2.5对哮喘发病的影响。目前关于PM2.5对免疫系统影响及与哮喘发病关系方面还有待更深入的研究。近年来发现调节性T细胞和胸腺基质淋巴细胞生成素在哮喘发病中发挥重要作用。但国内外尚无针对PM2.5对二者影响的深入研究。本课题将通过研究PM2.5对Th1/Th2平衡及Toll样受体表达的影响，对调节性T细胞的数量及功能的影响以及对胸腺基质淋巴细胞生成素表达的影响，探讨PM2.5引发哮喘发病的免疫学机制。为积极预防哮喘发病，制定合理的大气污染防治措施提供实验依据。

流行病学数据显示近20年来我国哮喘的发病率呈明显上升趋势。已有研究显示PM2.5暴露与哮喘加重有明显相关性。据此我们提出科学问题：PM2.5暴露是否会增加哮喘发病的风险以及其作用机制是什么。本课题通过小鼠构建了PM2.5暴露的动物模型，实验发现PM2.5在小鼠致敏后暴露可以加重哮喘的气道炎症，在小鼠致敏前PM2.5联合OVA刺激可以引发轻度气道炎症反应。动物实验提示PM2.5暴露可能促进哮喘的发病。本课题进一步探索研究了PM2.5诱发哮喘的机制。实验结果显示PM2.5联合OVA刺激可以使肺组织中IL-4 mRNA水平升高，IFN-γ/IL-4比例下降，提示PM2.5暴露可诱发Th1/Th2失衡。PM2.5联合OVA刺激可导致小鼠胸腺中Treg细胞比例减少，使肺组织中Th17/Treg比例下降，提示PM2.5暴露可影响Treg细胞及Th17/Treg平衡。PM2.5暴露可以使气道上皮细胞来源细胞因子IL-33的表达水平升高，并促进上皮凋亡，提示PM2.5可通过引起气道上皮损伤及刺激细胞因子释放促进哮喘发病。综上所述，本课题发现PM2.5暴露可促进哮喘发病，其机制与诱发Th1/Th2失衡、Th17/Tre失衡、影响气道上皮细胞等方面有关。