A novel mouse model of idiopathic pulmonary fibrosis established by in situ lung injection of bleomycin

<title>Abstract</title> <p> <bold>Background</bold> Drug induction, mechanical stimulation and gene editing are common strategies for idiopathic pulmonary fibrosis (IPF) mouse models, with bleomycin (BLM) the most widely used inducer. Classic intratracheal BLM instillation suffers from difficult operation and inconsistent lesions. This study established a novel left-lung in situ BLM injection model and evaluated nintedanib efficacy to resolve these drawbacks. <bold>Methods</bold> Tracer distribution was compared between intratracheal and in situ injection. Animal survival, body weight and pathological indexes were measured for model comparison. We set sham, BLM model and nintedanib treatment groups. Histological staining and qRT-PCR detected lung injury; Student’s t-test was adopted for statistics ( <italic>p &lt; 0.05</italic> ). <bold>Results</bold> In situ injection achieved uniform left-lung agent distribution. It induced typical IPF phenotypes (weight loss, inflammation, collagen deposition) with easier operation and higher animal survival than intratracheal instillation. Nintedanib notably alleviated lung fibrotic lesions in this new model. <bold>Conclusions</bold> This in situ BLM injection method is simple to master after short training, stable and suitable for routine preclinical IPF modeling and antifibrotic drug screening. </p>