过敏原诱导哮喘的鼠模型
2012/07/05
摘要
哮喘是一个常见疾病，具有一定的死亡率，全球有约3亿名哮喘患者。8%的美国人患有哮喘，而且患病率仍在上升。
与其他疾病一样，过敏性气道疾病的动物模型有助于了解哮喘的病理生理学，帮助发现潜在的治疗靶点和对可能的新治疗方法进行临床前研究。目前，已经在诸多物种中建立了过敏性气道疾病的模型，其中在鼠类建立的动物模型尤为关注，因为该模型建立费用较低、方便，而且对这些动物的免疫系统也比较了解；一些转基因动物的出现丰富了这些动物模型。
本文描述过敏性气道疾病的2种鼠类模型，其中均采用卵清白蛋白作为抗原诱导。通过腹腔注射致敏后，其中一个模型通过雾化吸入进行抗原激发，另一个模型则通过气管内给药。这两个模型具有互补的优势，每个都模拟了人体哮喘的主要特征。急性哮喘的主要特征包括气道对刺激物（乙酰甲胆碱）的反应性增加（又称之为气道高反应性，AHR）和嗜酸性粒细胞性气道炎症。这些表现在上述2种鼠类过敏原激发的模型中尤为明显。我们同时介绍了检测这些指标和评价了实验操作影响的方法。特别是对检测气道高反应性的有创和无创方法及评价气道和肺炎症细胞浸润的方法进行了介绍。通过支气管肺泡灌洗液收集气道炎症细胞，对肺进行组织病理学检查，评价炎症标志物。这些技术是研究哮喘的有用手段。
（苏楠 审校）
J Vis Exp. 2012 May 14;(63). pii: 3771. doi: 10.3791/3771.
J Vis Exp. 2012 May 14;(63). pii: 3771. doi: 10.3791/3771.
Source
Department of Medicine, Division of Pulmonary, Allergy and Critical Care Medicine, Emory University and Atlanta VA Medical Center.
Abstract
Asthma is a major cause of morbidity and mortality, affecting some 300 million people throughout the world. (1) More than 8% of the US population has asthma, with the prevalence increasing.(2) As with other diseases, animal models of allergic airway disease greatly facilitate understanding of the underlying pathophysiology, help identify potential therapeutic targets, and allow preclinical testing of possible new therapies. Models of allergic airway disease have been developed in several animal species, but murine models are particularly attractive due to the low cost, ready availability, and well-characterized immune systems of these animals.(3) Availability of a variety of transgenic strains further increases the attractiveness of these models.(4) Here we describe two murine models of allergic airway disease, both employing ovalbumin as the antigen. Following initial sensitization by intraperitoneal injection, one model delivers the antigen challenge by nebulization, the other by intratracheal delivery. These two models offer complementary advantages, with each mimicking the major features of human asthma.(5) The major features of acute asthma include an exaggerated airway response to stimuli such as methacholine (airway hyperresponsiveness; AHR) and eosinophil-rich airway inflammation. These are also prominent effects of allergen challenge in our murine models,(5,6) and we describe techniques for measuring them and thus evaluating the effects of experimental manipulation. Specifically, we describe both invasive(7) and non-invasive(8) techniques for measuring airway hyperresponsiveness as well as methods for assessing infiltration of inflammatory cells into the airways and the lung. Airway inflammatory cells are collected by bronchoalveolar lavage while lung histopathology is used to assess markers of inflammation throughout the organ. These techniques provide powerful tools for studying asthma in ways that would not be possible in humans.
J Vis Exp. 2012 May 14;(63). pii: 3771. doi: 10.3791/3771.
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住处距离主干道的远近与儿童哮喘控制特征相关
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过敏性哮喘患者支气管肺泡灌洗液外切酶体与细胞因子和白三烯的产生
