实验动物与比较医学 ›› 2025, Vol. 45 ›› Issue (2): 167-175.DOI: 10.12300/j.issn.1674-5817.2024.120

• 人类疾病动物模型 • 上一篇    下一篇

常见哮喘动物模型的建立方法与评价研究进展

罗世雄1, 张赛2, 陈慧2()   

  1. 1.天津中医药大学, 天津 300193
    2.天津中医药大学第二附属医院, 天津 300250
  • 收稿日期:2024-08-21 修回日期:2025-01-25 出版日期:2025-04-25 发布日期:2025-04-25
  • 通讯作者: 陈 慧(1973—),女,博士,主任医师,硕士研究生导师,研究方向:中西医结合儿科临床和基础研究。E-mail: erkechenhui@sohu.com。ORCID: 0009-0003-2757-8486
  • 作者简介:罗世雄(1998—),女,硕士研究生,研究方向:中医儿科常见疾病。E-mail:574761907@qq.com
  • 基金资助:
    天津市教委科研计划项目“基于EGFR/MPAK信号通路研究小青龙汤抑制哮喘气道黏液高分泌的效应及作用机制”(2022KJ177)

Research Progress in Establishment and Evaluation of Common Asthma Animal Models

LUO Shixiong1, ZHANG Sai2, CHEN Hui2()   

  1. 1.Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China
    2.The Second Affiliated Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin 300250, China
  • Received:2024-08-21 Revised:2025-01-25 Published:2025-04-25 Online:2025-04-25
  • Contact: CHEN Hui (ORCID:0009-0003-2757-8486), E-mail: erkechenhui@sohu.com

摘要:

支气管哮喘(简称哮喘)是一种以气道炎症、气道高反应性和气道重塑为特征的常见的慢性呼吸系统疾病,其发病机制复杂且具有异质性,涉及遗传、免疫、环境等多种因素。目前针对哮喘的治疗手段相对有限,深入探究哮喘的发病机制、探寻有效的治疗方法以及开发新型药物已成为当务之急。因此,哮喘动物模型的建立至关重要。然而,至今仍没有一种理想的哮喘动物模型能够全面、准确地复刻人类哮喘发生与发展的所有特征。本文对近5年来哮喘动物模型建立方法的研究进展进行了系统梳理,详细综述了常见实验动物(如小鼠、大鼠、豚鼠)、常见致敏剂(包括卵清蛋白、屋尘螨、脂多糖、甲苯二异氰酸酯),以及用常见实验动物及致敏剂建立哮喘动物模型的方法,并对这些模型的优缺点和适用范围进行了客观评价。本文总结了哮喘模型的评价指标,涉及行为学、肺功能、病理学、免疫学、药效学等多个方面。难治性哮喘动物模型的建立方式虽尚未完善,但通过相关文献检索,总结了难治性哮喘动物模型造模的几种思路,旨在为相关研究提供有价值的参考。根据现有的科学技术,笔者推测未来哮喘动物模型的研究将更加聚焦于临床相关性、技术创新以及多学科融合。具体而言,未来哮喘动物模型将通过多重致敏原联合诱导并应用基因编辑等新技术,提升模型的临床相关性,实现模型的多样化与个性化,并使用生物成像、传感技术动态监测哮喘气道炎症及气道重塑等相关反应,甚至可利用芯片技术寻找动物模型替代方法,最终致力于开发出更能模拟人类哮喘复杂性和异质性的多因素复合模型。

关键词: 哮喘, 动物模型, 评价指标, 致敏剂

Abstract:

Bronchial asthma (hereinafter referred to as asthma) is a common chronic respiratory disease characterized by airway inflammation, airway hyperresponsiveness, and airway remodeling. Its pathogenesis is highly complex and heterogeneous, involving multiple factors such as genetics, immunity, and environmental exposure. Currently, therapeutic options for asthma remain relatively limited, making it an urgent priority to explore its underlying mechanisms, identify effective treatment strategies, and develop new drugs. In this context, the establishment of animal models for asthma plays an irreplaceable and crucial role. However, to date, no single ideal animal model has been able to fully and accurately replicate all the features of the onset and progression of human asthma. This study systematically reviews the research progress over the past five years in the establishment methods of asthma animal models. It provides a detailed overview of commonly used experimental animals (such as mice, rats, and guinea pigs), frequently used sensitizing agents (including ovalbumin, house dust mite, lipopolysaccharide, and toluene diisocyanate), and the methods for establishing asthma models using these animals and sensitizers. This study also presents an objective evaluation of the advantages, limitations, and applicability of each model. Evaluation criteria for asthma models are summarized across multiple dimensions, including behavioral assessments, pulmonary function, histopathology, immunological indicators, and pharmacodynamics. Although methods for establishing refractory asthma models remain underdeveloped, several strategies for modeling refractory asthma have been summarized through a review of relevant literature, aiming to provide useful references for related research. Based on current scientific and technological advancements, it is anticipated that future research on asthma animal models will focus more on clinical relevance, technological innovation, and multidisciplinary integration. Specifically, future models are expected to adopt multi-sensitizer induction protocols, apply cutting-edge tools such as gene editing, enhance clinical relevance and promote diversification and personalization of models. Furthermore, advanced technologies such as bioimaging and biosensing are anticipated to enable dynamic monitoring of airway inflammation and remodeling. Organ-on-a-chip platforms may also be explored as potential alternatives to traditional animal models. The ultimate goal is to develop multifactorial, composite models that better simulate the complexity and heterogeneity of human asthma.

Key words: Asthma, Animal model, Evaluation criteria, Sensitizing agents

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