白介素17抗体减轻吸烟所致慢性阻塞性肺疾病模型小鼠的气道炎症

摘要

目的 研究白介素17(interhukin-17,IL-17)抗体在吸烟所致慢性阻塞性肺疾病(chronic obstructive pulmonary disease,COPD)模型小鼠气道炎症中的作用.方法 C67/BL6雄性小鼠随机分为COPD组(8只)、COPD+IL-17抗体干预组(简称COPD+干预组,8只)和正常对照组(10只).对支气管肺泡灌洗液(BALF)进行细胞计数、染色和分类;用酶联免疫吸附试验检测小鼠肺组织匀浆IL-17水平,观察各组小鼠气道病理改变.结果 COPD组与COPD+干预组相比肺功能差异无统计学意义.COPD组、COPD+干预组小鼠与正常对照组相比BALF细胞总数显著增高[分别为(19.64±1.89)×104/ml,(15.47±2.99)×104/ml和(5.13±1.00)×104/ml,P＜0.01];COPD+干预组较COPD组细胞总数下降(P＜0.01);中性粒细胞比例[分别为(8.58+6.77)%,(22.98±8.46)%]及绝对值[(1.28±0.96)×104/ml,(4.53±1.73)×104/ml]显著下降(P值均＜0.01).肺组织HE染色病理评分COPD+干预组(73.25±18.58)较cOPD组(106.13±36.27)炎症有所减轻(P＜0.05).COPD+干预组小鼠肺组织匀浆中IL-17含量(0.084±0.041)pg/mg pro与COPD组(0.221±0.081)pg/mg pro相比显著降低(P＜0.01).结论 吸烟所致COPD小鼠模型中IL-17参与了中性粒细胞引起的气道炎症,抑制IL-17的表达,可以减少气道内中性粒细胞的数量,减轻气道炎症.%Objective To investigate the significance of interleukin-17(IL-17)antibodies in cigarette smoke-induced chronic obstructive pulmonary disease(COPD)in mice.Methods Male C57/BL6 mice were randomly divided into COPD group(n=8),COPD+anti-IL-17 Ab group(n=8),and normal control group (n=10).The Rumher of cells in bronchoalveolar lavage fluid(BALF)was calculated and the concentrations of IL-17 in lung tissues was measured by enzyme-linked immunosorbent assay.Histoiogic analysis of the lungs was done in each group.Results The intra-airway pressure(IP),peak expiratory flow(PEF),and Ip slope in anti-IL-17 Ab group were insignificant compared with those of COPD group.The total cell count in BALF was significantly higher in COPD group than in normal control group(P＜0.01).Compared with COPD group.the total cell count in COPD+anti-IL-17 Ab group was decreased[(19.64±1.89)×104/ml and(15.47±2.99)×104/ml(P＜0.01)],neutrophils in BALF were obviously decreased,(22.98±8.46)%,(8.58±6.77)%(P＜0.01).The airway inflammation was alleviated in COPD+anti-IL-17 Ab group by histologic analysis.The concentration of IL-17 in lung tissue was significantly lower in COPD+anti-IL-17 Ab group [(0.084±0.041)pg/mg Pro] than in the COPD group[(0.221±0.081)pg/mg pro](P＜0.01).Conclusions IL-17 might play a role in airway neutrophilic inflammation in cigarette smoke-induced COPD in mice.Anti-IL-17 could decrease the Rumbet of neutrophils in the BALF and attenuate the neutrophilic airway inflammation.