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目的为阐明胸腺基质淋巴生成素受体(Thymic stromal lymphopoietin receptor,TSLPR)在超敏原引起的气道炎症应答中的作用,并在小鼠模型中探讨局部封闭TSLPR用以缓解哮喘的可能性。方法对TSLPR抗体或同型抗体预处理,且以鸡卵白蛋白(OVA)诱导的各组小鼠,分别行气道浸润细胞的分类和记数、H&E和PAS的肺组织染色分析;并以酶联免疫吸附测定法(ELISA)检测支气管肺泡灌洗液中炎性细胞因子;进一步分析OVA激发的小鼠树突状细胞(DCs)的迁移能力和成熟状态。结果在小鼠OVA致敏前施以抗TSLPR抗体可显著减少气道粘液的分泌、嗜酸性粒细胞和淋巴细胞浸润;同时引发IL-4、IL-5水平的明显下降。而作为其机制之一,TSLPR的中和作用可阻止超敏原诱导的DCs的成熟和迁移。结论封闭TSLPR介导的信号通路可缓解哮喘小鼠的气道炎症反应,有望成为一项新的防治气道变应性疾病策略。
Objective To elucidate the role of thymic stromal lymphopoietin receptor (TSLPR) in response to allergen-induced airway inflammation and to explore the possibility of local blockade of TSLPR in asthmatic mice in a mouse model. Methods TSLPR antibody or isotype antibody was pretreated, and the classification and counting of airway infiltrating cells, lung tissue staining of H & E and PAS in each group induced by chicken ovalbumin (OVA) were performed. Inflammatory cytokines in bronchoalveolar lavage fluid were detected by immunoadsorbent assay (ELISA). Migration capacity and maturation status of OVA-stimulated mouse dendritic cells (DCs) were further analyzed. Results Anti-TSLPR antibody administration before OVA sensitization in mice could significantly reduce airway mucus secretion, eosinophil and lymphocyte infiltration; at the same time, the levels of IL-4 and IL-5 were significantly decreased. As one of its mechanisms, the neutralization of TSLPR can prevent the maturation and migration of hypersensitive DCs. Conclusion Blocking the TSLPR-mediated signaling pathway can alleviate the airway inflammatory response in asthmatic mice and is expected to become a new strategy to prevent and treat airway allergic disease.