Liu Tianju, De Los Santos Francina Gonzalez, Phan Sem H
Department of Pathology, University of Michigan Medical School, Ann Arbor, MI, USA.
Methods Mol Biol. 2017;1627:27-42. doi: 10.1007/978-1-4939-7113-8_2.
Interstitial lung disease (ILD) comprises a large number of chronic lung disease characterized by varying degrees of inflammation and fibrosis. Mostly they are idiopathic including idiopathic pulmonary fibrosis (IPF), which is a specific disorder characterized by progressive fibrosis leading commonly to end-stage lung disease, respiratory failure, and fatal outcome. IPF and many of these fibrotic ILDs lack effective therapy despite recent approval of two drugs to slow progression in certain IPF patients. Because there are no natural models for IPF, the use of animal models that reproduce key known features of the disease is warranted. Thus, different animal models have been developed to investigate key mechanisms underlying pathogenesis of pulmonary fibrosis and identify potential therapeutic targets for IPF. While no animal model can recapitulate all features of human disease, several are available to address select features of IPF and other fibrotic ILDs. Historically, among the first to be developed and used widely is the bleomycin model, which is the best-characterized and currently most extensively used animal model due to its ability to reproduce many aspects of IPF and other fibrotic ILDs, good reproducibility, and ease of induction. Studies using the bleomycin model have identified many of the cellular and molecular mechanisms now recognized as being important in pathogenesis of IPF and other fibrotic ILDs, as well as novel therapies for these diseases, including two recent drugs approved for treatment of IPF. This chapter will describe commonly used techniques for induction of the model by endotracheal administration of bleomycin through surgical and nonsurgical (transoral instillation).
间质性肺疾病（ILD）包括大量以不同程度炎症和纤维化为特征的慢性肺部疾病。其中大多数是特发性的，包括特发性肺纤维化（IPF），这是一种特定的疾病，其特征是进行性纤维化，通常导致终末期肺病、呼吸衰竭和致命结局。尽管最近有两种药物被批准用于减缓某些IPF患者的病情进展，但IPF和许多这些纤维化ILD仍缺乏有效的治疗方法。由于没有IPF的天然模型，因此有必要使用能够重现该疾病关键已知特征的动物模型。因此，已经开发出不同的动物模型来研究肺纤维化发病机制的关键机制，并确定IPF的潜在治疗靶点。虽然没有动物模型能够概括人类疾病的所有特征，但有几种模型可用于研究IPF和其他纤维化ILD的特定特征。历史上，最早开发并广泛使用的是博来霉素模型，由于它能够重现IPF和其他纤维化ILD的许多方面、良好的可重复性以及易于诱导，它是特征最明确且目前使用最广泛的动物模型。使用博来霉素模型的研究已经确定了许多现在被认为在IPF和其他纤维化ILD发病机制中很重要的细胞和分子机制，以及这些疾病的新疗法，包括最近批准用于治疗IPF的两种药物。本章将描述通过手术和非手术（经口滴注）经气管内给予博来霉素诱导该模型的常用技术。
