Effects of ozone repeated short exposures on the airway/lung inflammation, airway hyperresponsiveness and mucus production in a mouse model of ovalbumin-induced asthma
Effects of ozone repeated short exposures on the airway/lung inflammation, airway hyperresponsiveness and mucus production in a mouse model of ovalbumin-induced asthma
复制标题
臭氧反复短时间暴露对卵清蛋白诱发哮喘小鼠模型气道/肺部炎症、气道高反应性和粘液产生的影响
DOI：
10.1016/j.biopha.2018.02.079
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发表时间：
2018-05-01
影响因子：
7.5
通讯作者：
Zhou, Xin
中科院分区：
文献类型：
--
作者：
Bao, Wuping;Zhang, Yingying;Zhou, Xin
目的：本研究旨在探讨臭氧反复短时间暴露对卵清蛋白（OVA）致敏/激发哮喘小鼠模型气道/肺炎症、气道高反应性（AHR）和气道高分泌的影响。臭氧暴露（3 ppm，3小时）在雾化OVA激发后1小时给予（隔日1次，共4次）。进行乙酰甲胆碱（MCH）支气管激发试验、支气管肺泡灌洗液（BALF）细胞涂片刘氏染色、肺组织苏木素-伊红（HE）染色和高碘酸-希夫（PAS）染色。白细胞介素（IL）;检测小鼠肺组织中IL-4、IL-13、IL-1 β和IL-18蛋白（ELISA）和mRNA表达水平（RT-qPCR），支气管肺泡灌洗液（BALF）中8-羟基脱氧鸟苷（8-OHdG，ELISA）、丙二醛（MDA，硫代巴比妥酸法）、还原型谷胱甘肽（GSH，分光光度法）和肺组织中GSH 1 mRNA相对表达水平（RT-qPCR）。反复臭氧暴露下调了接受OVA致敏和激发的小鼠对MCH的AHR，但并非所有与哮喘相关的参数都降低，因为明显的粘液高分泌诱导了气道炎症轻微增加，特别是在小气道周围。臭氧联合染毒可逆转OVA致敏/激发引起的小鼠肺组织IL-4和IL-13水平的升高。相反，BALF中IL-1 β的水平仍然高于阴性对照组。结论：AHR并不能准确反映哮喘小鼠哮喘的严重程度。反复短时间臭氧暴露增加粘液分泌过多，可能是通过增加氧化应激和免疫失调。
Objective: The purpose of this study is to explore the influence of ozone repeated short exposures on airway/lung inflammation, airway hyperresponsiveness (AHR) and airway hypersecretion in ovalbumin (OVA) sensitized/challenged asthmatic mouse model.Methods: OVA sensitization was performing by intraperitoneal injection. Ozone exposures (3ppm for 3hours) were given one hour after aerosolized OVA challenges (once every other day, 4 times totally). Methacholine (MCH) bronchial provocation tests, Liu's staining of BALF cell smears, hematoxylin-eosin (HE) staining and Periodic Acid-Schiff (PAS) staining of lung tissue were performed. Interleukins (ILs; IL-4, IL-13, IL-1 beta, and IL-18) protein (ELISA) and mRNA expression levels (RT-qPCR) in murine lung, 8-hydroxy-2'-deoxyguanosine (8-OHdG, ELISA), malondialdehyde (MDA, thiobarbituric acid assay), reduced glutathione (GSH, spectrophotometric method) in bronchoalveolar lavage fluid (BALF), and GSH1 mRNA relative expression levels (RT-qPCR) in lung tissue were analyzed.Result: Repeated ozone exposures down-regulated the AHR to MCH in mice undergoing OVA sensitization and challenge, however not all parameters associated with asthma were decreased since obvious mucus hypersecretion was induced and airway inflammation increased slightly, especially around small airways. Following ozone co-exposure, the increase of IL-4 and IL-13 levels in murine lung caused by OVA sensitization/challenge were reversed. Instead, levels of IL-1 beta in BALF remained, higher than negative control group. Ozone repeated short exposures also induced significant increase of 8-OHdG in BALF in OVA sensitized and challenged mice.Conclusion: For asthmatic mice undergoing ozone exposures, AHR is not an accurate indicator of the severity of asthma. Repeated short ozone exposures increase mucus hypersecretion, possibly via an increase in oxidative stress and immune dysregulation.