PM2.5对哮喘大鼠呼吸道黏膜上皮病理损伤及炎症的影响

Effects of PM2.5 on the pathological injury and inflammation of airway epithelium in asthmatic rats

目的探讨PM2.5对哮喘大鼠呼吸道黏膜上皮病理损伤和炎症的影响。方法124只SD大鼠随机分为对照组、哮喘组、哮喘大鼠+PM2.5小剂量组、哮喘大鼠+PM2.5大剂量组。HE染色观察气道黏膜、肺组织病理改变;qRT-PCR检测肺组织TOLL样受体2(TLR2)、β防御素2(RBD2)的mRNA水平;免疫组化检测肺组织TLR2、RBD2蛋白表达;ELISA试剂盒检测支气管肺泡灌洗液(BALF)中白细胞介素6(IL-6)、白细胞介素8(IL-8)及血清总免疫球蛋白E(IgE)含量。结果哮喘大鼠暴露于PM2.52周时,呼吸道黏膜上皮细胞纤毛减少,炎症反应加重;哮喘大鼠暴露于小剂量PM2.52周时TLR2及RBD2表达增加;哮喘大鼠暴露于小剂量PM2.52周时,BALF中IL-8含量明显增加,4周时IL-6含量明显增加,IL-8增高早于IL-6;暴露于小剂量PM2.5第4周时,哮喘大鼠血清IgE含量明显增高。结论PM2.5可加重呼吸道黏膜上皮损伤,其机制与PM2.5导致TLR2、RBD2表达增加,引起气道炎症反应有关。

Objective To investigate the effect of PM2.5 on the pathological changes and the inflammation in lung of asthmatic rats.Methods The rats were randomly divided into control group,asthmatic group,low dose PM2.5 group,and high dose PM2.5 group.Pathological changes of airway mucosa and lung were observed by HE staining.The mRNA levels of TLR2 and RBD2 of lung tissue were detected by qRT-PCR.The expressions of TLR2 and RBD2 were evaluated by immunohistochemistry.Levels of IL-6,IL-8 in bronchoalveolar lavage fluid(BALF)and IgE content in serum were detected with ELISA kits.Results The cilia of the airway epithelial cells in asthmatic rats were decreased and the inflammation was increased at 2 weeks after PM2.5 exposure.The expressions of TLR2 and RBD2 in asthmatic rats were significantly increased at 2 weeks after exposure at low dose of PM2.5.The level of IL-8 in BALF of asthmatic rats were significantly increased at 2 weeks after exposure at low dose of PM2.5,and the level of IL-6 increased at 4 weeks.And the time point of the IL-8 elevation was also earlier than that of IL-6.After 4-week low dose of PM2.5 exposure,level of IgE in serum was also significantly increased.Conclusion PM2.5 can aggravate respiratory mucosal epithelial injury,and the mechanism is related to the increased expression of TLR2 and RBD2 caused by PM2.5,which leads to airway inflammation.