香烟烟雾暴露诱导慢性阻塞性肺疾病小鼠模型的构建及多维度病理评估

doi:10.12300/j.issn.1674-5817.2025.076

实验动物与比较医学 ›› 2026, Vol. 46 ›› Issue (1): 11-19.DOI: 10.12300/j.issn.1674-5817.2025.076

香烟烟雾暴露诱导慢性阻塞性肺疾病小鼠模型的构建及多维度病理评估

何家祺(), 周园园, 聂永强, 王朝霞, 徐汪节()()

上海交通大学实验动物中心, 上海 200240

收稿日期:2025-05-20 修回日期:2025-08-20 出版日期:2026-02-25 发布日期:2026-02-14
作者简介:何家祺（1998—），男，硕士研究生，研究方向：实验动物模型建立与评估。E-mail：122080910005@sjtu.edu.cn。ORCID：0009-0009-6266-2994
XU Wangjie (ORCID: 0009-0007-2049-5169), E-mail:hover_xwj@sjtu.edu.cn
徐汪节，博士，上海交通大学副研究员，毕业于上海交通大学，康奈尔大学访问学者。现任上海交通大学实验动物中心副主任，硕士生导师，兼职教育部学位与研究生教育发展中心教育评估专家、科技部评审专家，中医药慢病防治与教育会常务委员等。迄今为止，主持或参与国家863计划、国家自然科学基金、科技部重点研发项目子课题等项目13项，在FEBS J、PNAS、Int J Biochem Cell Biol等国际期刊发表SCI论文40余篇，并申请专利5项（获批2项）。曾获中国科协科研仪器优秀案例、上海市教学成果奖（二等奖）、上海市分析测试会科学技术奖等各类奖项8项，以及中国分析测试学会卓越工程师、《实验动物与比较医学》杂志优秀青年编委等荣誉称号7项。（1977—），男，博士，副研究员，研究方向：环境因素与生殖发育，实验动物模型研究。E-mail：hover_xwj@sjtu.edu.cn。ORCID：0009-0007-2049-5169
基金资助:
2023年度上海交通大学决策咨询立项课题-实验技术专项“基于自研烟雾暴露设备研制慢性阻塞性肺疾病小动物模型”(JCZXSJA2023-02);国家重点研发计划“SPF及无菌动物繁育与应用技术体系建立”(2024YFD1800404);细胞工程及抗体药物教育部工程研究中心创新研发课题“NMIBC ADC药物的体内药效学及毒副作用研究”(24X010201938-005)

Establishment and Multidimensional Pathological Evaluations of a Cigarette Smoke Exposure-Induced Chronic Obstructive Pulmonary Disease Mouse Model

HE Jiaqi(), ZHOU Yuanyuan, NIE Yongqiang, WANG Zhaoxia, XU Wangjie()()

Laboratory Animal Center of Shanghai Jiao Tong University, Shanghai 200240, China

Received:2025-05-20 Revised:2025-08-20 Published:2026-02-25 Online:2026-02-14

摘要/Abstract

摘要：

目的基于自研设备“多通道小动物长时连续烟雾暴露的自动控制系统”，采用新型香烟烟雾连续暴露方法，建立稳定可靠的慢性阻塞性肺疾病（chronic obstructive pulmonary disease，COPD）小鼠模型，并进行表型评估分析，为研究COPD发病机制及防治策略提供动物实验基础。方法 20只6周龄雄性C57BL/6J小鼠被随机分成对照组和模型组，每组10只。模型组小鼠每日进行6 h连续烟雾暴露（6支香烟/d，持续12周），对照组小鼠无干预。小鼠每隔2周进行一次体重监测；造模结束后，对小鼠进行小动物CT（micro-CT）活体成像；小鼠安乐死后，用ELISA法检测小鼠血清与支气管肺泡灌洗液中炎症因子白细胞介素-6（interleukin-6，IL-6）和肿瘤坏死因子-α（tumor necrosis factor-α，TNF-α）的水平；对肺组织进行HE染色和Masson染色检测，观察肺组织形态和炎症细胞含量的变化，计算小鼠肺泡平均截距（mean linear intercept，MLI），以综合评估小鼠模型的COPD临床特征。结果从第4周开始，与对照组相比，模型组小鼠体重显著降低（P<0.01）。ELISA检测结果显示，与对照组相比，模型组小鼠血清和支气管肺泡灌洗液中的IL-6质量浓度分别增高了27.2%和140.0%，差异均具有统计学意义（P<0.01）；与对照组相比，模型组小鼠血清和支气管肺泡灌洗液中的TNF-α浓度分别增高了16.7%（P<0.01）和19.3%（P<0.05）。HE染色结果显示，与对照组相比，模型组小鼠肺泡壁变薄，肺泡出现不同程度扩张，部分肺泡间隔断裂，融合成肺大泡，肺泡数量减少，支气管管壁变厚，管腔变窄，周围有炎症细胞浸润，MLI显著增大（P<0.01）。Masson染色结果显示，模型组小鼠出现胶原沉积及支气管重塑。Micro-CT结果显示，模型组小鼠出现局部高密度影，呈现出慢性支气管炎的典型特征。结论自研装置可实现长期连续烟雾暴露，构建的COPD小鼠模型病理特征与临床症状高度吻合，可为COPD研究提供高效可靠的工具。

关键词: 慢性阻塞性肺疾病, 香烟烟雾暴露, 小鼠模型, 自研设备, 连续暴露

Abstract:

Objective To establish a reliable chronic obstructive pulmonary disease (COPD) mouse model based on a self-developed multichannel automatic control system for long-term continuous cigarette smoke exposure in small animals using a novel continuous cigarette smoke exposure method, and to conduct phenotypic evaluation and analysis, thereby providing an animal experimental basis for investigating COPD pathogenesis and prevention strategies. Methods Twenty male C57BL/6J mice aged 6 weeks were randomly and equally divided into a control group and a model group. The model group (n=10) underwent 6 h of continuous cigarette smoke exposure daily (6 cigarettes per day for 12 consecutive weeks), while the control group (n=10) received no intervention. Body weight was monitored biweekly. Post-exposure, in vivo micro-CT imaging was performed. After euthanasia, serum and bronchoalveolar lavage fluid (BALF) levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were quantified by ELISA. Lung tissues underwent H&E and Masson's trichrome staining to observe changes in lung morphology and inflammatory cell infiltration, and the mean linear intercept (MLI) was calculated, thereby comprehensively evaluating the clinical features of COPD in the mouse model. Results Compared with the control group, the model group showed significantly reduced body weight (P<0.01) from the fourth week. Compared with the control group, IL-6 level in the serum and BALF of the model group increased by 27.2% and 140.0%, respectively (P<0.01). TNF-α level in the serum and bronchoalveolar lavage fluid of the model group increased by 16.7% (P<0.01) and 19.3% (P<0.05), respectively. Histopathological examination revealed alveolar wall thinning, septal rupture, emphysematous bullae formation, reduced alveolar count, bronchial wall thickening with lumen narrowing, and inflammatory cell infiltration. MLI was significantly elevated (P<0.01). Masson's staining confirmed collagen deposition and bronchial remodeling. Micro-CT demonstrated localized high-density shadows exhibiting typical features of chronic bronchitis. Conclusion The self-developed device enables long-term continuous smoke exposure, and the successfully established COPD mouse model exhibits pathological features highly consistent with clinical manifestations, offering an efficient and reliable tool for COPD research.

Key words: Chronic obstructive pulmonary disease, Cigarette smoke exposure, Mouse model, Self-developed device, Continuous exposure

中图分类号:

Q95-33

何家祺,周园园,聂永强,等. 香烟烟雾暴露诱导慢性阻塞性肺疾病小鼠模型的构建及多维度病理评估[J]. 实验动物与比较医学, 2026, 46(1): 11-19. DOI: 10.12300/j.issn.1674-5817.2025.076.

HE Jiaqi,ZHOU Yuanyuan,NIE Yongqiang,et al. Establishment and Multidimensional Pathological Evaluations of a Cigarette Smoke Exposure-Induced Chronic Obstructive Pulmonary Disease Mouse Model[J]. Laboratory Animal and Comparative Medicine, 2026, 46(1): 11-19. DOI: 10.12300/j.issn.1674-5817.2025.076.

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香烟烟雾暴露诱导慢性阻塞性肺疾病小鼠模型的构建及多维度病理评估

Establishment and Multidimensional Pathological Evaluations of a Cigarette Smoke Exposure-Induced Chronic Obstructive Pulmonary Disease Mouse Model

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