IL-17A功能抑制对小鼠氧化应激模型中性粒细胞炎症及气道高反应性的影响

Influence of interleukin-17A inhibition on airway neutrophils and hyperresponsiveness in an oxidative stress mouse model

目的 探讨IL-17A功能抑制对臭氧（O3）所致小鼠氧化应激模型中性粒细胞炎症及气道高反应性（AHR）的影响.方法 32只C57/BL6小鼠随机分成4组：空气暴露＋PBS干预组,空气暴露＋IL-17A单克隆抗体（IL-17mAb）干预组,O3暴露＋PBS干预组,O3暴露＋IL-17mAb干预组,检测AHR,对BALF行细胞计数、肺组织HE染色观察气道炎症病理改变并检测炎症细胞浸润程度及肺气肿分数,酶联免疫吸附（ELISA）法测定BALF中肿瘤坏死因子α（TNF-α）,IL-8和IL-17A水平.结果 IL-17mAb干预的O3暴露组较PBS组能降低AHR、BALF中炎症细胞总数、中性粒细胞数、IL-8和IL-17A水平,差异均有统计学意义.结论 O3所致氧化应激可引起中性粒细胞炎症及AHR.IL-17A功能抑制可通过减少炎症细胞数量及浸润程度,抑制相关细胞因子如IL-8、IL-17A等过度表达,改善由于氧化应激导致的气道炎症反应及AHR.

Objective To explore the effects of interleukin-17A inhibition on airway neutrophils and hyperresponsivenessin an oxidative stress model .Methods The C57/BL6 mice were randomly divided into four groups：air-exposed＋ PBS-treated model ,air-exposed＋ IL-17mAb-treated model ,ozone-exposed＋PBS-treated model ,ozone-exposed ＋ IL-17mAb-treated model .Mice were studied 24 hours after final exposure , monitoring bronchial responsiveness , airway inflammatory cells , lung histology , levels of neutrophil-related chemokine and proinflammatory cytokines in bronchoalveolar lavage fluid （ BALF） , airway inflammatory cells infiltration density and emphysema scores .Results IL-17mAb reduced total inflammatory cells , especially neutrophils , and airway inflammatory cells infiltration density . It also decreased levels of IL-8 and IL-17A in BALF ,mitigated airway hyperresponsiveness ,when compared with the administration of a control PBS .Conclusions IL-17mAb may inhibit oxidative stress-induced airway neutrophils and hyperresponsiveness .