Center for Medical Research, Medical University of Graz, 8010 Graz, Austria.
Research Center Pharmaceutical Engineering GmbH, 8010 Graz, Austria.
Int J Mol Sci. 2024 Mar 1;25(5):2903. doi: 10.3390/ijms25052903.
The respiratory barrier, a thin epithelial barrier that separates the interior of the human body from the environment, is easily damaged by toxicants, and chronic respiratory diseases are common. It also allows the permeation of drugs for topical treatment. Animal experimentation is used to train medical technicians, evaluate toxicants, and develop inhaled formulations. Species differences in the architecture of the respiratory tract explain why some species are better at predicting human toxicity than others. Some species are useful as disease models. This review describes the anatomical differences between the human and mammalian lungs and lists the characteristics of currently used mammalian models for the most relevant chronic respiratory diseases (asthma, chronic obstructive pulmonary disease, cystic fibrosis, pulmonary hypertension, pulmonary fibrosis, and tuberculosis). The generation of animal models is not easy because they do not develop these diseases spontaneously. Mouse models are common, but other species are more appropriate for some diseases. Zebrafish and fruit flies can help study immunological aspects. It is expected that combinations of in silico, in vitro, and in vivo (mammalian and invertebrate) models will be used in the future for drug development.
呼吸屏障是一层薄薄的上皮屏障,将人体内部与环境隔开,容易受到毒物的损害,慢性呼吸道疾病也很常见。它还允许药物渗透进行局部治疗。动物实验用于培训医疗技术人员、评估毒物和开发吸入制剂。呼吸道结构的物种差异解释了为什么有些物种比其他物种更能预测人类的毒性。有些物种可用作疾病模型。本文描述了人和哺乳动物肺的解剖学差异,并列出了目前用于最相关的慢性呼吸道疾病(哮喘、慢性阻塞性肺疾病、囊性纤维化、肺动脉高压、肺纤维化和肺结核)的常用哺乳动物模型的特征。由于这些动物不会自发地患上这些疾病,因此动物模型的生成并不容易。小鼠模型很常见,但其他物种更适合某些疾病。斑马鱼和果蝇可以帮助研究免疫学方面。预计未来药物开发将结合使用计算机模拟、体外和体内(哺乳动物和无脊椎动物)模型。