Wang Jingyu, Zhu Fengqing, Liu Yuxuan, Luo Renru, Fan Zixuan, Dai Wanqin, Wei Shuquan, Lin Chuwen
Department of Pulmonary and Critical Care Medicine, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, China.
Department of Histology and Embryology, School of Medicine, Shenzhen Campus of Sun Yat-Sen University, Sun Yat-Sen University, Shenzhen, China.
Biochem Cell Biol. 2025 Jan 1;103:1-7. doi: 10.1139/bcb-2024-0221.
Idiopathic pulmonary fibrosis (IPF) is a progressive and irreversible lung disease with high mortality and limited treatment options. While single-dose bleomycin-induced models are commonly used to investigate the pathogenesis of IPF, they fail to adequately replicate the complex pathological features in human patients, thereby hindering comprehensive investigations. Previous studies utilizing repetitive bleomycin injections have demonstrated a closer resemblance to human IPF pathology; however, the time- and resource-intensive nature of this approach presents significant drawbacks. Here, we propose a novel methodology involving twice-repeated oropharyngeal administration of bleomycin in mice, which closely mirrors the pathological manifestations observed in IPF patients. This model exhibited the honeycomb-like cyst formation, fibroblastic foci, bronchiolization of alveolar epithelium, emergence of metaplastic alveolar KRT5 basal cells, and sustainability of these fibrotic phenotypes, thereby providing a robust model for IPF. Our findings establish a more efficient and translatable preclinical platform for investigating IPF pathogenesis and exploring potential therapeutic strategies.
特发性肺纤维化（IPF）是一种进行性且不可逆的肺部疾病，死亡率高且治疗选择有限。虽然单剂量博来霉素诱导的模型常用于研究IPF的发病机制，但它们无法充分复制人类患者的复杂病理特征，从而阻碍了全面的研究。先前利用重复注射博来霉素的研究表明，其与人类IPF病理学更为相似；然而，这种方法在时间和资源上的高消耗性存在显著缺点。在此，我们提出一种新方法，即对小鼠进行两次重复的博来霉素经口咽给药，这与IPF患者中观察到的病理表现极为相似。该模型表现出蜂窝状囊肿形成、成纤维细胞灶、肺泡上皮细支气管化生、化生的肺泡KRT5基底细胞出现以及这些纤维化表型的持续性，从而为IPF提供了一个可靠的模型。我们的研究结果建立了一个更高效且可转化的临床前平台，用于研究IPF发病机制和探索潜在治疗策略。
