不同内型哮喘小鼠模型中的小气道功能研究及其机制初探  

Characteristics and mechanisms of smallairway function in different asthma mice models

作　　者：薛艺抒 傅强[1] 包婺平 郝慧娟 张旻[1] XUE Yi-shu;FU Qiang;BAO Wu-ping;HAO Hui-juan;ZHANG Min(Department of Respiratory and Critical Care Medicine,the Shanghai First People's Hospital Affiliated to Shanghai Jiaotong University,Shanghai 200080,China)

机构地区：[1]上海交通大学附属第一人民医院呼吸与危重症医学科,上海200080

出　　处：《临床肺科杂志》2022年第3期351-357,共7页Journal of Clinical Pulmonary Medicine

基　　金：国家自然科学基金(No.81873402)。

摘　　要：目的探讨不同内型哮喘小鼠模型中,小气道功能是否存在异常及其相关机制。方法卵清蛋白(OVA)致敏、激发建立T2型哮喘模型,OVA联合臭氧暴露(OVA+ozone)建立非T2型哮喘模型。模拟强迫振荡系统检测小鼠小气道功能,激发试验检测气道反应性。酶联免疫吸附试验法检测支气管肺泡灌洗液(BALF)中的细胞因子;苏木精-伊红染色法对肺切片进行病理分析,免疫组织化学方法检测肺组织中的α-平滑肌肌动蛋白。结果T2型和非T2型哮喘模型中均存在大、小气道功能障碍,显著的气道炎症、气道高反应性以及气道重塑,并有BALF中炎性细胞因子升高。OVA+ozone组呈现更显著的中性粒细胞浸润。小气道功能代表性指标,平均呼气中期流量和用力呼气50%肺活量与BALF中炎性细胞因子水平、气道反应性、气道平滑肌增生均表现出较好的相关性。结论T2型和非T2型的哮喘小鼠模型中均存在小气道功能障碍。小气道功能可能受到气道炎症、气道反应性以及气道重塑的共同影响,参与哮喘的发生发展。Objective To explore whether there are abnormalities in small airway function in different types of asthma mouse models and the underlying mechanisms.Methods Ovalbumin(OVA)was sensitized and stimulated to establish a T2 asthma model,and OVA combined with ozone exposure(OVA+ozone)to establish a non-T2 asthma model.The small-airway function was measured by the EMMS FM system,and airway responsiveness can be measured by the bronchial provocation test.Enzyme-linked immunosorbent assay(ELISA)was used to detect cytokines in bronchoalveolar lavage fluid(BALF);hematoxylin-eosin staining was used for the pathological analysis of lung slices,and immunohistochemical method was used to detectα-smooth muscle actin in lung tissue.Results Both T2 and non-T2 asthma models have large and small airway dysfunction,severe airway inflammation,airway hyperresponsiveness,and airway remodeling,and there is an increase in inflammatory cytokines in BALF.The OVA+ozone group showed more significant neutrophil infiltration.The representative indicators of small airway function,mean mid-expiratory flow(MMEF),and forced expiratory flow at 50%of FVC(FEF50)showed a good correlation with the levels of inflammatory cytokines,airway responsiveness,and airway smooth muscle hyperplasia in BALF.Conclusion There are small airway dysfunctions in both T2 and non-T2 asthma mouse models.Small airway function may be affected by airway inflammation,airway responsiveness,and airway remodeling,and participate in the occurrence and development of asthma.

关 键 词：小气道功能 气道炎症 哮喘 气道高反应性 

分 类 号：R562.25[医药卫生—呼吸系统] R-332[医药卫生—内科学]