寒冷气候对PM2.5致呼吸道损害效应的影响及其相关分子背景

Cold air often leads to the frequently-occurring or exacerbation of respiratory diseases. The concentrations of PM2.5 in the atmospheric haze also showed a clear correlation with respiratory tract damage. The impact and molecular mechanism of cold climate and stimulation of PM2.5 play important roles to respiratory tract damage in cold regions of northern China where they are just high-incidence areas of PM2.5 air pollution. The purpose of this research is to observe the change characterization of exosyndrome of airway mucus cilia system and biochemical activities of airway epithelial cell in cold climate,and detect the secondary effects of PM2.5 invade airway under cold temperature. These results will be helpful to reveal the role and relationship between cold air and concentration of PM2.5 to respiratory tract damage. To achieve the goal we will establish a rat model of cold injury and cell stressed model.Firstly, we detect drift state of mucin phenotype 5AC/5B that shows the self purification capacity of airway. secondly, we examine the expression, localization and transportion of cold inducible RNA-binding protein (CIRP) in vivo and vitro. Thirdly, we detect the co-localization of CIRP and stress granules in active cells as well as interaction.Finally, we measure the concentrations of inflammatory factors, mucin and other indexes under stimulation of PM2.5 compared with normal temperature.Thus, the identification of CIRP-mediated infiltration of inflammatory mediators induced by cold temperature and PM2.5 might help to interpret mechanism of respiratory tract damage.these results will probably provide new intervention targets to respiratory tract damage caused by cold temperature and stimulation of PM2.5.

寒冷气候常导致呼吸道疾病的多发或病情加重，而大气PM2.5浓度也呈现出与呼吸道损害明确相关的规律，考虑到我国北方寒冷地区正是PM2.5污染高发区域，故两者效应的互动机制有着突出的重要性。本课题旨在研究寒冷气候下呼吸道黏液纤毛系统的表征和气道上皮细胞相关炎性反应的改变特点，及此背景下受到PM2.5侵袭所呈现的继发效应，揭示寒冷环境对PM2.5损害效应的影响及分子机制。实验通过寒冷环境下大鼠和培养细胞模型，观察反映气道自净能力的粘蛋白5AC/5B表型的飘移状态，以及细胞应对冷环境的重要调控因子冷诱导RNA结合蛋白（CIRP）的表达、胞内定位及位移情况，并对CIRP和应激颗粒的相互作用和胞内共定位行动态追踪。在此背景下进一步施加PM2.5刺激，与常温条件比对观察炎性因子产生、粘蛋白分泌等指标，以期阐明寒冷气候下PM2.5损害效应的特点及相关转录后调控机制，为防控PM2.5的危害提供新的干预靶点。

冷空气导致呼吸道疾病病情加重和病患增多，而大气PM2.5浓度也呈现出与呼吸道损害明确相关的规律，冷空气和PM2.5相互叠加对呼吸道疾病加重及多发有着突出的重要性。我国北方寒冷地区正是PM2.5污染高发区域，本课题通过构建低温环境下PM2.5染毒的离体培养气道上皮细胞和动物模型，观察PM2.5+冷刺激双重条件下，炎症反应形态学特点及炎症因子水平的改变特点，明确了寒冷气候可对PM2.5致呼吸道损害产生不可忽略的增效作用， 增效作用可能CIRP/eIF2α实现的，明确低温环境下气道黏液纤毛系统的功能改变特点及表层粘蛋白的飘移状态。同时课题组还基于转化应用预期的考虑，还延展研究探讨了传统植物药用成分苦味素及其受体对PM2.5诱导气道上皮细胞炎症的影响及干预机制，进一步得出结论，传统治咳喘的中药组分可引起支气管上皮细胞 T2R14 激活，抑制慢性炎症气道的炎症因子产生和释放，提示T2R14 可能参与苦味组份的抗炎过程，为慢性气道炎症性疾病的防治提供了新的理论启示。

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