近年来，在呼吸系统疾病的临床前研究中，如器官样和器官组织芯片模型方面已有突破性进展，但仍无法很好地揭示人类呼吸系统疾病。由于保留了肺结构和主要细胞类型，人类肺片模型是呼吸系统疾病研究的有前途的体外模型。人类肺片是手工制备的，从进行肺手术的肺癌患者的小块肺组织中获得。为评估这种模型在肺纤维化研究中的适用性，将肺片分别用CdCl2（30μM）、TGF-β1（1ng/ml）或CdCl2加TGF-β1处理3天，然后进行毒性评估、基因表达分析和组织病理学观察。CdCl2处理导致浓度依赖性的毒性表现，证实了MTT试验和组织病理学观察。与未处理组相比，CdCl2和TGF-β1显著诱导MMP2和MMP9基因表达，但不诱导MMP1。有趣的是，CdCl2加TGF-β1明显诱导MMP1的表达，但不影响MMP2、MMP7或MMP9。显微镜观察显示，所有组的肺片显示间质性肺纤维化的病理生成，但CdCl2加TGF-β1处理导致肺泡隔厚度更大和成纤维细胞病灶状的病理特征。肺片模型缺乏血液供应，炎症/免疫反应被认为很小。结果支持假说，特发性肺纤维化（IPF）是由组织损伤和异常修复介导的。诱导MMP1基因表达和成纤维细胞病灶的发生表明该模型可能代表IPF的早期阶段。©2023.作者。

In recent years, there have been breakthroughs in the preclinical research of respiratory diseases, such as organoids and organ tissue chip models, but they still cannot provide insight into human respiratory diseases well. Human lung slices model provides a promising in vitro model for the study of respiratory diseases because of its preservation of lung structure and major cell types.Human lung slices were manually prepared from small pieces of lung tissues obtained from lung cancer patients subjected to lung surgery. To evaluate the suitability of this model for lung fibrosis research, lung slices were treated with CdCl2 (30 μM), TGF-β1 (1 ng/ml) or CdCl2 plus TGF-β1 for 3 days followed by toxicity assessment, gene expression analysis and histopathological observations.CdCl2 treatment resulted in a concentration-dependent toxicity profile evidenced by MTT assay as well as histopathological observations. In comparison with the untreated group, CdCl2 and TGF-β1 significantly induces MMP2 and MMP9 gene expression but not MMP1. Interestingly, CdCl2 plus TGF-β1 significantly induces the expression of MMP1 but not MMP2, MMP7 or MMP9. Microscopic observations reveal the pathogenesis of interstitial lung fibrosis in the lung slices of all groups; however, CdCl2 plus TGF-β1 treatment leads to a greater alveolar septa thickness and the formation of fibroblast foci-like pathological features. The lung slice model is in short of blood supply and the inflammatory/immune-responses are considered minimal.The results are in favor of the hypothesis that idiopathic pulmonary fibrosis (IPF) is mediated by tissue damage and abnormal repair. Induction of MMP1 gene expression and fibroblast foci-like pathogenesis suggest that this model might represent an early stage of IPF.© 2023. The Author(s).