实验动物与比较医学2026，Vol.46Issue(4)：498-506,9.DOI:10.12300/j.issn.1674-5817.2025.169
免疫检查点抑制剂相关性肺炎小鼠模型的构建与评价
Construction and Evaluation of Mouse Models Simulating Immune Checkpoint Inhibitor-Associated Pneumonitis
摘要
Abstract
Objective To construct and evaluate a mouse model that simulates the pathological progression of immune checkpoint inhibitor-associated pneumonitis(CIP),in order to address the critical issue of the lack of standardized animal models in this research field.Methods Thirty-five SPF-grade 6-week-old male C57BL/6J mice were randomly assigned to a control group(n=5),a bleomycin(BLM)group(n=15),and a BLM+programmed death-1(PD-1)monoclonal antibody(BLM+PD-1)group(n=15).Corresponding drugs were administered via intraperitoneal injection for intervention.The general condition,body weight changes,survival rate,and pulmonary histopathological alterations were systematically monitored.Results Compared with the BLM group,the BLM+PD-1 group exhibited significantly more severe pulmonary fibrosis,characterized by progressive body weight loss and more severe deterioration of general conditions.Histopathological examination showed that pulmonary inflammation was alleviated 4 weeks post-modeling in the BLM group.In contrast,pulmonary lesions continued to worsen in the BLM+PD-1 group,with no evidence of resolution of inflammation 28 days post-modeling.Quantitative immunohistochemical analysis revealed that the positive expression rate of interleukin-17A(IL-17A)in lung tissues reached 34.28%in the BLM+PD-1 group 14 days post-modeling,which was markedly higher than that in the BLM group(24.02%,P<0.000 1).The positive expression rate of α-smooth muscle actin(α-SMA)was 12.40%in the BLM+PD-1 group 14 days post-modeling,nearly twice the level in the BLM group(5.87%).28 days post-modeling,the positive expression rate of α-SMA remained at 7.72%in the BLM+PD-1 group,while it declined to 3.38%in the BLM group.Conclusion The addition of a PD-1 inhibitor to bleomycin treatment accelerates the progression of pulmonary interstitial fibrosis and effectively recapitulates the pathological process of lung injury and fibrosis driven by aberrant immune activation during clinical immunotherapy.Accordingly,this study successfully establishes a dynamic CIP animal model recapitulating the progression from early inflammatory response to pulmonary fibrosis.This model addresses the critical shortage of animal models for this condition and offers an experimental platform for further mechanistic studies and the development of therapeutic strategies.关键词
免疫检查点抑制剂/免疫检查点抑制剂相关性肺炎/小鼠模型/博来霉素/肺纤维化Key words
Immune checkpoint inhibitors/Immune checkpoint inhibitor-associated pneumonitis/Mouse model/Bleomycin/Pulmonary fibrosis分类
医药卫生引用本文复制引用
龚志群,饶希午,张天弋,吴荣琛,叶明楠,蒋春曦,王苏美,朱燕娟,柴小姝..免疫检查点抑制剂相关性肺炎小鼠模型的构建与评价[J].实验动物与比较医学,2026,46(4):498-506,9.基金项目
国家自然科学基金"益肺散结丸调控DOT1L介导的H3K79甲基化抑制STAT3/CD15轴抗肺癌免疫逃逸的机制"(82305340) （82305340）
广东省中医院国自然培育专项"加味苇茎汤抑制ICAM1/LFA-1 介导的T细胞异常活化防治ICIs诱发免疫性相关肺炎的机制研究"(YN2024GZRPY039) （YN2024GZRPY039）
