细颗粒物上的焦油成分对哮喘模型小鼠气道炎症的影响及其机制研究

Some reports suggest that short-term increase of the concentration of particulate matter less than or to equal 2.5 microns (PM2.5) may lead to the increase of hospital admissions for asthma. Airway inflammation is a major contributing factor to asthma. Our previous study has shown that the organic substances and chemicals adhering to PM2.5 may contribute to the aggravation of murine airway inflammation induced by OVA, however, it’s unclear which substance adhering to PM2.5 play a key role in the aggravation of murine airway inflammation. On the other hand, another study suggest that Tar adhering to Asian sand dust (ASD), contribute to the aggravation of murine airway inflammation induced by OVA. Therefore, in the present study, mice were intratracheally challenged with different levels of Tar, to investigate the effect of Tar adhering to PM2.5 on OVA-induced murine airway inflammation. And then, the suppressive effects of three MAPK specific inhibitors on murine airway inflammation caused by OVA and Tar were studied, the expressions of some proteins in this signal pathway were measured, to explore the meachanisms mediating the adverse health effect of PM2.5, and provide scientific data for the prevention and treatment of asthma.

环境中空气动力学直径小于或等于2.5微米的颗粒物（particulate matter less than or to equal 2.5 microns, PM2.5）浓度升高可导致哮喘发病增加，而气道炎症是其中主要促进因素。前期的研究显示PM2.5上附着的各种物质可加剧卵蛋白（ovalbumin, OVA）诱导的小鼠气道炎症，但到底是何种物质在其中发挥着关键的作用尚不清楚，而亚洲沙尘颗粒物上附着的焦油（Tar）加剧了OVA诱导的小鼠气道炎症。所以本研究拟以不同剂量、从PM2.5提取的Tar对OVA诱导的小鼠进行干预，观察对其气道炎症的影响；再以三种丝裂原活化蛋白激酶（mitogen-activated protein kinase, MAPK）的特异性抑制剂对该哮喘小鼠进行干预，观察其MAPK信号通路相关蛋白的表达，以求为阐明PM2.5的毒作用机制和防治哮喘提供科学资料。

中文摘要.环境中空气动力学直径小于或等于2.5微米的颗粒物（particulate matter less than or to equal 2.5 microns, PM2.5）浓度升高可导致哮喘发病增加，而气道炎症是其中主要促进因素。前期的研究显示PM2.5上附着的各种物质可加剧卵蛋白（ovalbumin, OVA）诱导的小鼠气道炎症，但到底是何种物质在其中发挥着关键的作用尚不清楚，而亚洲沙尘颗粒物上附着的焦油（Tar）加剧了OVA诱导的小鼠气道炎症。所以本研究拟以不同剂量、从PM2.5提取的Tar对OVA诱导的小鼠进行干预，观察对其气道炎症的影响；再以三种丝裂原活化蛋白激酶（mitogen-activated protein kinase, MAPK）的特异性抑制剂对该哮喘小鼠进行干预，观察其MAPK信号通路相关蛋白的表达，以求为阐明PM2.5的毒作用机制和防治哮喘提供科学资料。.我们的实验结果发现：（1）本地区冬季采暖季节，大气中PM2.5上附着的Tar含量，以及Tar中PAHs含量均较高。（2）PM2.5上附着的Tar可以通过升高炎症因子和抗原特异性抗体的水平，加剧OVA诱导的气道炎症。（3）细胞外调节蛋白激酶(extracellular regulated protein kinase, ERK) 的特异性抑制剂，PD98059减轻了OVA与Tar联合作用导致的小鼠气道炎症。这些结果表明Tar加剧OVA诱导的气道炎症的作用可能部分是由ERK信号通路介导的，这提示ERK的特异性抑制剂，如PD98059对PM2.5导致的哮喘加剧可能会有一定的防治作用。