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四周屋尘螨诱导的变应性气道炎症伴气道重塑模型。

A 4-Week Model of House Dust Mite (HDM) Induced Allergic Airways Inflammation with Airway Remodeling.

机构信息

Division of Respirology and Multi-Organ Transplant Programme, University Health Network, Faculty of Medicine, Toronto, Canada.

Division of Occupational and Environmental Health, Dalla Lana School of Public Health, University of Toronto, Toronto, Canada.

出版信息

Sci Rep. 2018 May 2;8(1):6925. doi: 10.1038/s41598-018-24574-x.

Abstract

Animal models of allergic airways inflammation are useful tools in studying the pathogenesis of asthma and potential therapeutic interventions. The different allergic airways inflammation models available to date employ varying doses, frequency, duration and types of allergen, which lead to the development of different features of asthma; showing varying degrees of airways inflammation and hyper-responsiveness (AHR) and airways remodeling. Models that also exhibit airway remodeling, a key feature of asthma, in addition to AHR and airway inflammation typically require 5-12 weeks to develop. In this report, we describe a 4-week mouse model of house dust mite (HDM)-induced allergic airways inflammation, and compare the phenotypic features of two different doses of HDM exposures (10 µg and 25 µg) for 5 days/week with a well-characterized 8-week chronic HDM model. We found that 4 weeks of intranasal HDM (25 µg in 35 µl saline; 5 days/week) resulted in AHR, airway inflammation and airway remodeling that were comparable to the 8-week model. We conclude that this new 4-week HDM model is another useful tool in studies of human asthma that offers advantages of shorter duration for development and decreased costs when compared to other models that require longer durations of exposure (5-12 weeks) to develop.

摘要

过敏性气道炎症的动物模型是研究哮喘发病机制和潜在治疗干预措施的有用工具。目前可用的不同过敏性气道炎症模型采用不同剂量、频率、持续时间和过敏原类型,导致哮喘的不同特征发展;表现出不同程度的气道炎症和高反应性(AHR)和气道重塑。除 AHR 和气道炎症外,还表现出气道重塑这一哮喘关键特征的模型通常需要 5-12 周才能发展。在本报告中,我们描述了一种为期 4 周的屋尘螨(HDM)诱导的过敏性气道炎症的小鼠模型,并比较了两种不同剂量的 HDM 暴露(10μg 和 25μg)每周 5 天与经过充分特征描述的 8 周慢性 HDM 模型的表型特征。我们发现,4 周的鼻腔内 HDM(25μg 在 35μl 盐水中;每周 5 天)导致 AHR、气道炎症和气道重塑,与 8 周模型相当。我们得出结论,与需要更长暴露时间(5-12 周)才能发展的其他模型相比,这种新的 4 周 HDM 模型是研究人类哮喘的另一种有用工具,其发展时间更短,成本更低。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2555/5932037/6dae2e9dad0f/41598_2018_24574_Fig1_HTML.jpg

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