Aun Marcelo Vivolo, Bonamichi-Santos Rafael, Arantes-Costa Fernanda Magalhães, Kalil Jorge, Giavina-Bianchi Pedro
Clinical Immunology and Allergy Division, Department of Internal Medicine, University of São Paulo School of Medicine, São Paulo, Brazil.
Laboratory of Experimental Therapeutics (LIM20), Department of Internal Medicine, University of Sao Paulo, Sao Paulo, Brazil.
J Asthma Allergy. 2017 Nov 7;10:293-301. doi: 10.2147/JAA.S121092. eCollection 2017.
Clinical studies in asthma are not able to clear up all aspects of disease pathophysiology. Animal models have been developed to better understand these mechanisms and to evaluate both safety and efficacy of therapies before starting clinical trials. Several species of animals have been used in experimental models of asthma, such as , rats, guinea pigs, cats, dogs, pigs, primates and equines. However, the most common species studied in the last two decades is mice, particularly BALB/c. Animal models of asthma try to mimic the pathophysiology of human disease. They classically include two phases: sensitization and challenge. Sensitization is traditionally performed by intraperitoneal and subcutaneous routes, but intranasal instillation of allergens has been increasingly used because human asthma is induced by inhalation of allergens. Challenges with allergens are performed through aerosol, intranasal or intratracheal instillation. However, few studies have compared different routes of sensitization and challenge. The causative allergen is another important issue in developing a good animal model. Despite being more traditional and leading to intense inflammation, ovalbumin has been replaced by aeroallergens, such as house dust mites, to use the allergens that cause human disease. Finally, researchers should define outcomes to be evaluated, such as serum-specific antibodies, airway hyperresponsiveness, inflammation and remodeling. The present review analyzes the animal models of asthma, assessing differences between species, allergens and routes of allergen administration.
哮喘的临床研究无法阐明疾病病理生理学的所有方面。已开发出动物模型，以更好地理解这些机制，并在开始临床试验之前评估治疗方法的安全性和有效性。哮喘实验模型中使用了几种动物，如大鼠、豚鼠、猫、狗、猪、灵长类动物和马。然而，在过去二十年中研究最多的动物是小鼠，尤其是BALB/c小鼠。哮喘动物模型试图模拟人类疾病的病理生理学。它们通常包括两个阶段：致敏和激发。传统上，致敏是通过腹腔和皮下途径进行的，但由于人类哮喘是由吸入过敏原引起的，鼻内滴注过敏原的方法越来越多地被使用。过敏原激发是通过气雾剂、鼻内或气管内滴注进行的。然而，很少有研究比较不同的致敏和激发途径。在开发良好的动物模型时，致病过敏原是另一个重要问题。尽管卵清蛋白更传统且会导致强烈炎症，但它已被气传过敏原（如屋尘螨）所取代，以便使用引发人类疾病的过敏原。最后，研究人员应确定要评估的结果，如血清特异性抗体、气道高反应性、炎症和重塑。本综述分析了哮喘动物模型，评估了不同物种、过敏原和过敏原给药途径之间的差异。
