Modeling asthma: Pitfalls, promises, and the road ahead.
Modeling asthma: Pitfalls, promises, and the road ahead.
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DOI：
10.1002/jlb.3mr1117-436r
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发表时间：
2018-07
影响因子：
5.5
通讯作者：
Druey KM
中科院分区：
文献类型：
--
作者：
Rosenberg HF;Druey KM
哮喘是一种慢性、异质性和反复发作的下气道炎症性疾病，其加重以气道炎症和支气管高反应性为特征。哮喘已经通过野生型和基因操纵的实验室小鼠（小家鼠）的疾病诱导进行了广泛的建模。抗原致敏和激发策略重现了人类哮喘气道炎症的许多重要特征，特别是Th2细胞因子的关键作用。最近的疾病诱导模型已经发展到包括生理性空气过敏原与长时间的呼吸挑战没有全身致敏；还有一些含有烟草、呼吸道病毒或细菌作为催熟剂。然而，肺大小、结构和生理反应的差异限制了在小鼠中测量的气道动力学可以与人类受试者进行比较的程度。其他啮齿类动物过敏气道模型，包括豚鼠（Cavia porcellus）可能被考虑用于肺功能研究。最后，家猫（猫科猫）和马（马）也会出现自发性阻塞性气道疾病，其临床和病理特征与人类哮喘相似。关于这些疾病的发病机制和治疗的信息是一个重要的资源。在这篇小型综述中，我们考虑了体内建模的原理以及用于研究人类哮喘的动物模型的具体特征。
Asthma is a chronic, heterogeneous and recurring inflammatory disease of the lower airways, with exacerbations that feature airway inflammation and bronchial hyperresponsiveness. Asthma has been modeled extensively via disease induction in both wild-type and genetically manipulated laboratory mice (Mus musculus). Antigen sensitization and challenge strategies have reproduced numerous important features of airway inflammation characteristic of human asthma, notably the critical roles of Th2 cytokines. Recent models of disease induction have advanced to include physiologic aeroallergens with prolonged respiratory challenge without systemic sensitization; others incorporate tobacco, respiratory viruses or bacteria as exacerbants. Nonetheless, differences in lung size, structure and physiologic responses limit the degree to which airway dynamics measured in mice can be compared to human subjects. Other rodent allergic airways models, including those featuring the guinea pig (Cavia porcellus) might be considered for lung function studies. Finally, domestic cats (Feline catus) and horses (Equus caballus) develop spontaneous obstructive airway disorders with clinical and pathologic features that parallel human asthma. Information on pathogenesis and treatment of these disorders is an important resource. In this mini-review we consider the principles of in vivo modeling together with specific features of animal models for the study of human asthma.