博来霉素联合猪胰弹性蛋白酶诱导的小鼠肺纤维化合并肺气肿模型的建立

doi:10.16352/j.issn.1001-6325.2026.06.0800

基础医学与临床 ›› 2026, Vol. 46 ›› Issue (6): 800-806.doi: 10.16352/j.issn.1001-6325.2026.06.0800

博来霉素联合猪胰弹性蛋白酶诱导的小鼠肺纤维化合并肺气肿模型的建立

高艺丹^1,2#, 郭丽娜^2#, 王爽^1,2, 张红², 宋婉璐², 胡宇飞^2*, 杨沛然^1,2*

1.内蒙古医科大学基础医学院,内蒙古呼和浩特 010110;
2.中国医学科学院北京协和医学院基础医学研究所呼吸和共病全国重点实验室,北京 100005

收稿日期:2026-03-21 修回日期:2026-04-10 出版日期:2026-06-05 发布日期:2026-05-27
通讯作者: ^*peiran.yang@foxmail.com;hyf20@ibms.pumc.edu.cn
基金资助:
中国医学科学院中央级公益性科研院所基本科研业务费专项资金(2021-RC310-016)

Establishment of a mouse model of combined pulmonary fibrosis and emphysema induced by bleomycin and porcine pancreatic elastase

GAO Yidan^1,2#, GUO Lina^2#, WANG Shuang^1,2, ZHANG Hong², SONG Wanlu², HU Yufei^2*, YANG Peiran^1,2*

1. School of Basic Medical Sciences, Inner Mongolia Medical University, Hohhot 010110;
2. State Key Laboratory of Respiratory and Comorbidity, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100005,China

Received:2026-03-21 Revised:2026-04-10 Online:2026-06-05 Published:2026-05-27
Contact: ^*peiran.yang@foxmail.com;hyf20@ibms.pumc.edu.cn

摘要/Abstract

摘要： 目的建立一种以博来霉素(BLM)联合猪胰弹性蛋白酶(PPE)经气管滴入诱导的小鼠肺纤维化合并肺气肿(CPFE)模型。方法将雄性C57BL/6小鼠随机分为对照组和模型组。模型组小鼠接受气管滴入BLM(2.5 mg/kg)和PPE (1.5 U/100 g) 混悬液。对照组滴入磷酸盐缓冲液(PBS)。4周后进行肺功能检测,采用苏木精-伊红染色观察肺组织病理形态学变化,检测肺泡平均线性截距(MLI),采用马松三色染色法染色评估纤维化程度并测定气道上皮下胶原沉积厚度(SEc/Pbm),同时检测肺组织羟脯氨酸含量。结果与对照组相比,模型组的功能残气量(FRC)增加, FEV₅₀(第50 ms的用力呼气量)/FVC降低,最大呼气中段流量(MMEF)降低,动态肺顺应性(Cdyn)有降低趋势,吸气量(IC)基本不变,弦顺应性(Cchord)基本不变。组织学显示,模型组小鼠肺组织部分区域肺泡间隔增大,肺泡壁断裂,气管和部分肺组织伴有明显胶原沉积,此外MLI、SEc/Pbm及羟脯氨酸含量均显著增加。结论采用BLM联合PPE经气管滴入,可在4周内于C57BL/6小鼠成功建立兼具肺气肿样损伤和纤维化改变的CPFE模型,为后续CPFE发生发展的机制研究及干预策略评价提供实验基础。

关键词: 肺纤维化合并肺气肿, 小鼠模型, 肺纤维化, 肺气肿

Abstract: Objective To establish a mouse model of combined pulmonary fibrosis and emphysema (CPFE) induced by intratracheal instillation of bleomycin (BLM) combined with porcine pancreatic elastase (PPE). Methods Male C57BL/6 mice were randomly divided into a control group and an experimental group. Mice in the experimental group received intratracheal instillation of a suspension of BLM (2.5 mg/kg) and PPE (1.5 U/100 g). The control group received instillation of phosphate-buffered saline (PBS). After four weeks, lung function was assessed. Histopathological changes in lung tissue were observed using hematoxylin-eosin staining, and the mean linear intercept (MLI) was measured. Fibrosis severity was evaluated using Masson′s trichrome staining, and the subepithelial collagen deposition thickness (SEc/Pbm) in the airways was determined. Additionally, hydroxypro-line content in lung tissue was measured. Results Compared with the control group, the experimental group showed an increase in functional residual capacity (FRC), a decrease in FEV₅₀ (forced expiratory volume at 50 ms)/FVC and maximum mid-expiratory flow (MMEF), a trend toward decreased dynamic pulmonary compliance (Cdyn), no significant change in inspiratory capacity (IC), and no significant change in chord compliance (Cchord). Histologically, the experimental group exhibited enlarged alveolar septa and alveolar wall disruption in some lung regions, along with significant collagen deposition in the airways and parts of the lung parenchyma. Furthermore, MLI, SEc/Pbm, and hydroxyproline content were all significantly increased. Conclusions Intratracheal instillation of BLM combined with PPE successfully establishes a CPFE model in C57BL/6 mice within four weeks, characterized by both emphysema-like damage and fibrotic changes. This model provides an experimental basis for future research on the mechanisms underlying the development and progression of CPFE and for evaluating intervention strategies.

Key words: combined pulmonary fibrosis and emphysema, mouse model, pulmonary fibrosis, emphysema

中图分类号:

R563

高艺丹, 郭丽娜, 王爽, 张红, 宋婉璐, 胡宇飞, 杨沛然. 博来霉素联合猪胰弹性蛋白酶诱导的小鼠肺纤维化合并肺气肿模型的建立[J]. 基础医学与临床, 2026, 46(6): 800-806.

GAO Yidan. Establishment of a mouse model of combined pulmonary fibrosis and emphysema induced by bleomycin and porcine pancreatic elastase[J]. Basic & Clinical Medicine, 2026, 46(6): 800-806.

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博来霉素联合猪胰弹性蛋白酶诱导的小鼠肺纤维化合并肺气肿模型的建立

Establishment of a mouse model of combined pulmonary fibrosis and emphysema induced by bleomycin and porcine pancreatic elastase

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