AIM:To investigate the effects of perfluorooctanoic acid(PFOA)exposure on the changes of asth-matic mouse airway inflammation,inflammatory mediators interleukin-4(IL-4)and interferon-γ(IFN-γ)in serum, and glucocorticoid receptor(GR)expression in the lung tissue.METHODS:BALB/c mice(n=30)were randomly divided into 5 groups:normal control(C)group,asthma(A)group,asthma+low-dose PFOA(AP10)group,asthma+mode-rate-dose PFOA(AP50)group and asthma+high-dose PFOA(AP100)group.Asthma model and PFOA exposure model of mice were established according to the grouping.The animals were sacrificed and their lungs were collected for HE stai-ning,transmission electron microscopy,Western blot and immunohistochemical staining.ELISA was applied to detect the levels of IL-4 and IFN-γin the serum.RESULTS: HE staining of the lungs showed that the asthmatic mice, compared with the normal control mice,had obvious mucus secretion around the airways and infiltration of inflammatory cells around airways and blood vessels,and the effects were much more marked in AP groups.Ultrastructural alteration of the lung tis-sues in the asthmatic mice were indicated by transmission electron microscopy.Compared with C group, the results of ELISA in A group and AP groups proved that IL-4 in the serum was increased and IFN-γwas decreased significantly(P<0.05).Compare with A group,IL-4 was significantly increased and IFN-γwas decreased in AP100 group(P<0.05), and no difference of those between AP 10 group and AP50 group was found.The results of Western blot indicated that GR protein expression in the asthmatic mice were decreased compare with the normal mice(P<0.05), and no difference of that among A group and AP groups was observed.Immunohistochemical staining manifested that GR protein was mainly lo-cated in the cytoplasm of bronchial columnar epithelial cells,airway smooth muscle cells and vascular smooth muscle cells. CONCLUSION:Acute airway PFOA exposure in asthmatic mice dose-dependently exacebates lung inflammation by indu-cing Th2 type immune responses, promotes infiltration of inflammatory cells and mucus secretion around the airways and blood vessels,and destroys the ultrastructure of the lung tissues.%目的:研究全氟辛酸(PFOA)对哮喘小鼠气道炎症、外周血炎症介质白细胞介素4(IL-4)和干扰素γ(IFN-γ)以及肺组织糖皮质激素受体(GR)表达的影响及其可能机制.方法:30只BALB/c小鼠随机分为正常对照(C)组、哮喘模型(A)组、哮喘+PFOA低剂量(AP10)组、哮喘+PFOA中剂量(AP50)组和哮喘+PFOA高剂量(AP100)组,根据不同分组分别制作哮喘模型及PFOA暴露模型.留取肺组织标本后进行HE染色,透射电镜标本制作,ELISA法检测外周血IL-4及IFN-γ水平,并以Western blot及免疫组织化学染色法检测肺组织GR的蛋白表达.结果:肺组织病理切片HE染色结果显示,与正常小鼠相比,哮喘小鼠气道及血管周围可见明显的炎症细胞浸润及黏液分泌,AP各组表现更为明显.透射电镜结果显示,哮喘小鼠肺组织超微结构破坏明显.ELISA检测血清炎症因子结果表明,与C组相比,A组及AP各组外周血炎症因子IL-4升高,IFN-γ明显降低(P<0.05);与A组相比,AP10组及AP50组无明显差异,而AP100组外周血炎症因子IL-4升高,IFN-γ明显降低(P<0.05).Western blot结果显示哮喘小鼠肺组织GR表达较正常小鼠降低(P<0.05),而A组与AP各组之间无显著差异.免疫组化结果提示GR蛋白主要表达于小鼠肺组织支气管柱状上皮细胞、气道平滑肌细胞及血管平滑肌细胞胞浆.结论:哮喘小鼠气道PFOA急性暴露可通过诱导Th2型免疫反应加剧肺部炎症,促进气道及血管周围的炎症细胞浸润并破坏肺组织超微结构,且与剂量相关.
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