中国实验动物学报2026，Vol.34Issue(8)：1106-1119,14.DOI:10.3969/j.issn.1005-4847.2026.08.002
低滴度流感病毒-金黄色葡萄球菌共感染模型建立及对肺泡气血屏障的影响
Establishment of a low-titer influenza virus-Staphylococcus aureus co-infection model and its effect on the alveolar air-blood barrier
摘要
Abstract
Objective Establish a mouse model of co-infection with low-titer influenza virus and Staphylococcus aureus(H1N1-S.aureus)to recapitulate the mixed infection commonly observed in clinical practice,and investigate the effects on the alveolar-blood barrier in mice.Methods After pathogenicity screening of influenza virus and Staphylococcus aureus at different titers,a low-titer influenza-S.aureus co-infection mouse model was established in male BALB/c mice by intranasal administration of influenza virus(0.1 TCID50,20 μL)on day 0 and Staphylococcus aureus(1× 106 CFU,20 μL)on day 3.Using this model,host tissue damage and changes in alveolar adhesion and tight junction proteins were compared.Starting at 24 h after co-infection,the treatment was administered orally for three consecutive days.Hematoxylin and eosin(HE)staining was used to evaluate lung histopathological damage.The relative expression level of the influenza virus M gene in lung tissue was detected using reverse transcription quantitative PCR(RT-qPCR).The bacterial load in mouse lung tissue was determined by the spread plate method.Additionally,the gene and protein expression levels of air-blood barrier adhesion proteins and tight junction proteins in lung tissue were examined.Results Co-infection with a low titer of influenza virus(0.10 TCID50)and S.aureus(1 × 106 CFU)led to severe symptoms.In the H1N1-S.aaureus group,the mice exhibited a significant decrease in body mass,a marked reduction in the thymus index(P＜0.05),and a significant increase in the lung index(P＜0.05).The relative expression level of the M gene was significantly higher compared with the H1N1 group(P＜0.05),and the bacterial load was significantly higher compared with the S.aureus group(P＜0.05).Relative to the co-infection control group,the H1N1-S.aaureus group showed significantly decreased expression levels of Cadherin 5,ZO1,Claudin-5,and Occludin genes in lung tissue(P＜0.05),along with markedly elevated expression levels of the inflammatory cytokines IL-6,IL-1β,TNF-α and IFN-γ in lung tissue.Intervention with Chaihuguizhi decoction effectively alleviated the body mass loss trend in H1 N 1-S.aaureus group,reduced the expression levels of pulmonary inflammatory cytokines,and ameliorated lung inflammation.Conclusions In this study,we established a mouse model reflecting the characteristics of common clinical co-infections,and the pathogenic microbial replication and inflammatory factor damage were significantly higher than those in the separate infection group,and the intervention of the Chinese herbal medicine compound Chaihuguizhi decoction was able to attenuate the pathologic damage in the co-infection model.关键词
甲型H1N1流感病毒/金黄色葡萄球菌/共感染/肺气血屏障/紧密连接蛋白/柴胡桂枝汤Key words
H1N1 influenza virus/Staphylococcus aureus/co-infection/pulmonary blood-air barrier/tight junction proteins/Chaihuguizhi decoction分类
生物科学引用本文复制引用
徐令泽,容蓉,杨勇,刘孝云,林佳坤,朱明涵,叶冬雪,刘美怡,周万辉,程世娟,杨佳..低滴度流感病毒-金黄色葡萄球菌共感染模型建立及对肺泡气血屏障的影响[J].中国实验动物学报,2026,34(8):1106-1119,14.基金项目
国家自然科学基金(82274397),山东省技术创新引导计划(YDZX2023044),济南市市校融合发展战略工程项目(JNSX2023054),国家中医药管理局高水平中医药重点学科建设项目(ZYYZDXK-2023119),山东中医药大学科学研究基金项目(KY2024Z04),大学生创新创业训练计划项目(2024028).Funded by National Natural Science Foundation of China(82274397),Shandong Provincial Technology Innovation Guidance Program(YDZX2023044),Jinan Municipal-University Integration Development Strategic Project(JNSX2023054),Project for Constructing High-Level Key Disciplines of Traditional Chinese Medicine by the National Administration of Traditional Chinese Medicine(ZYYZDXK-2023119),Scientific Research Fund Project of Shandong University of Traditional Chinese Medicine(KY2024Z04),College Students' Innovation and Entrepreneurship Training Program(2024028). （82274397）
