摘要
目的比较两种致敏途径诱导的过敏性气道炎症小鼠模型的免疫炎症差异,为使用过敏性气道炎症小鼠模型的研究提供参考。方法建立卵清蛋白经腹腔致敏和经皮肤致敏诱导的过敏性气道炎症小鼠模型,通过ELISA分析小鼠血清中的总IgE和OVA特异性IgE。支气管肺泡灌洗液细胞行瑞士-吉姆萨染色以评估嗜酸性气道炎症。对肺组织进行苏木素伊红染色和高碘酸希夫染色以评估其组织病理学变化,肺免疫细胞进行mRNA测序和数据分析。结果经腹腔致敏和经皮致敏诱导的过敏性气道炎症小鼠模型均表现出肺组织嗜酸性粒细胞浸润、支气管上皮杯状细胞增生、Th2型细胞因子表达上调的炎症反应。但腹腔致敏模型系统免疫更强,经皮致敏模型局部免疫更强。哮喘相关通路如JAK-STAT信号通路在两个模型中均上调而Hippo通路仅在经皮致敏模型中下调。经皮致敏模型与金属蛋白酶、肥大细胞和嗜碱性粒细胞的关系更密切。结论过敏原经腹腔和经皮肤致敏途径不同,诱导产生的过敏性气道炎症小鼠模型的免疫学表型和分子机制存在差异。
Objective To compare the differences in airway immune inflammation between two sensitizationpathway-induced allergic airway inflammation mouse models and to provide a reference for the study of allergic asthma murine models.Methods Murine models of allergic airway inflammation were established by intraperitoneal or epicutaneous sensitization with ovalbumin.Total IgE and OVA-specific IgE levels in mouse serum were analyzed by ELISA.Bronchoalveolar lavage fluid cells were stained with Wright-Giemsa stain to assess eosinophilic airway inflammation.Hematoxylin and eosin and periodic acid-Schiff staining were performed on lung tissue to assess histopathological changes,and lung immune cells were subjected to mRNA sequencing and data analysis.Results Both intraperitoneal and epicutaneous sensitization-induced allergic airway inflammation mouse models exhibited inflammatory responses,with eosinophil infiltration of lung tissue,bronchial epithelial club cell hyperplasia,and upregulation of Th2-Type cytokine expression.However,systemic immunity was stronger in the intraperitoneal sensitization model,and local immunity was stronger in the epicutaneous sensitization model.Asthma-related pathways,such as the JAK-STAT signaling pathway,were upregulated in both models,whereas the Hippo pathway was downregulated only in the epicutaneous sensitization model.The epicutaneous sensitization model was more closely associated with the increase of metalloproteinases,mast cells,and basophils.Conclusions The different pathways of allergen intraperitoneal and epicutaneous sensitization induce different immunological phenotypes and molecular mechanisms of airway inflammation in mouse models of allergic airway inflammation.
作者
汤敏丹
李旭
张考苑
杨婷
卓凡
唐思怡
窦侠
陈小帆
TANG Mindan;LI Xu;ZHANG Kaoyuan;YANG Ting;ZHUO Fan;TANG Siyi;DOU Xia;CHEN Xiaofan(Shenzhen Peking University-the Hong Kong University of Science and Technology Medical Center,Shenzhen 518036,China;Department of Dermatology,Peking University Shenzhen Hospital,Shenzhen 518036)
出处
《中国比较医学杂志》
CAS
北大核心
2023年第4期11-19,共9页
Chinese Journal of Comparative Medicine
基金
国家自然科学基金面上项目(81972930)
深圳市科技计划基础研究面上项目(JCYJ20190809101015502)。
关键词
过敏性气道炎症
小鼠模型
致敏途径
转录组
免疫表型
allergic immune inflammation
murine model
sensitization
transcriptome
immunophenotype
