Efficacy of different doses of methylprednisolone on AECOPD mice induced by influenza A virus infection

XUE Lei; GUI Rui; ZENG Qiang; LI Wu; LIANG Cheng; ZHOU Weijia; DAI Xiaotian; DENG Guohong; XIONG Wei

doi:10.16016/j.2097-0927.202503041

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Efficacy of different doses of methylprednisolone on AECOPD mice induced by influenza A virus infection

Basic Medicine | 更新时间：2025-05-26

- Efficacy of different doses of methylprednisolone on AECOPD mice induced by influenza A virus infection
- Journal of Army Medical University Vol. 47, Issue 10, Pages: 1081-1091(2025)
- 作者机构：
  
  1.陆军军医大学（第三军医大学）第一附属医院：，老年医学与特勤医学科，重庆
  2.陆军军医大学（第三军医大学）第一附属医院：，感染科，重庆
  3.陆军军医大学（第三军医大学）第一附属医院：，呼吸与危重症科，重庆
  4.渝粤病理科学研究中心，重庆
- 作者简介：
  
  XIONG Wei， E-mail： xiongwei@tmmu.edu.cn；
- 基金信息：
  
  the National Key Research and Development Program(2018YFC2000301)
- DOI：10.16016/j.2097-0927.202503041
  CLC：
- Received：11 March 2025，
  
  Revised：07 April 2025，
  
  Published：30 May 2025
- 稿件说明：
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‍薛　磊，桂　锐，曾　强，等.不同剂量甲泼尼龙对甲型流感病毒感染诱导的AECOPD小鼠的疗效观察［J］.陆军军医大学学报，2025，47（10）：1081-1091.DOI：10.16016/j.2097-0927.202503041.

XUE L，GUI R，ZENG Q，et al.Efficacy of different doses of methylprednisolone on AECOPD mice induced by influenza A virus infection［J］.J Army Med Univ，2025，47（10）：1081-1091.DOI：10.16016/j.2097-0927.202503041.
‍薛　磊，桂　锐，曾　强，等.不同剂量甲泼尼龙对甲型流感病毒感染诱导的AECOPD小鼠的疗效观察［J］.陆军军医大学学报，2025，47（10）：1081-1091.DOI：10.16016/j.2097-0927.202503041. DOI：

XUE L，GUI R，ZENG Q，et al.Efficacy of different doses of methylprednisolone on AECOPD mice induced by influenza A virus infection［J］.J Army Med Univ，2025，47（10）：1081-1091.DOI：10.16016/j.2097-0927.202503041. DOI：

摘要

目的

探讨不同剂量甲泼尼龙（methylprednisolone， MP）对甲型流感病毒（influenza A virus，IAV）感染诱发慢性阻塞性肺疾病急性加重期（Acute exacerbation of chronic obstructive pulmonary disease，AECOPD）小鼠的治疗效应。

方法

通过LPS联合烟熏12周建立COPD小鼠模型，经鼻滴注IAV（40 μL）诱导AECOPD，建模成功后按照随机数字表法分5组（

=15）：低剂量甲泼尼龙组、中剂量甲泼尼龙组、高剂量甲泼尼龙组、奥司他韦组、空白组，观察10天内各组小鼠的体质量以及生存时间，于第1、3、5天使用WBP检测小鼠肺功能、ELISA法检测BALF炎症因子、空斑实验检测BALF病毒滴度、血平板检测BALF菌落形成单位。进行免疫荧光：①肺组织免疫荧光：将模型小鼠按照随机数字表法分3组（

=4）：将小鼠分为LPS 1天组、LPS 3天组、LPS+MP组，均予以LPS雾化1次，LPS+MP组在LPS雾化后予以MP灌胃1次，第1天取LPS 1天组肺组织，第3天取LPS 3天组和LPS+MP组肺组织，进行肺组织免疫荧光染色；②细胞免疫荧光：取小鼠骨髓中性粒细胞，分为空白组、LPS组、LPS+MP组、MP组，干预4 h后收集样本进行细胞免疫荧光检测。

结果

①中剂量甲泼尼龙组提高生存率、促进体质量恢复及改善肺功能效果最显著，相较于其余各组有明显差异（

0.05）。②中剂量甲泼尼龙组降低IL-6和中性粒细胞胞外捕获网（neutrophil extracellular traps，NETs）水平更显著（

0.05），高剂量甲泼尼龙

组治疗第5天出现炎症因子及NETs升高。③中剂量甲泼尼龙组的肺损伤评分下降较其余组均有显著差异（

0.05）。④高剂量甲泼尼龙组治疗第5天出现细菌大量增殖以及病毒清除延迟。

结论

中剂量甲泼尼龙对IAV诱导的 AECOPD 治疗效果最好，同时不会延迟病毒清除或增加病毒感染后细菌感染的风险。

Abstract

‍Objective‍　‍To investigate the efficacy of varying doses of methylprednisolone (MP) on mice with acute exacerbations of chronic obstructive pulmonary disease (AECOPD) induced with influenza A virus (IAV). Methods‍　‍Mouse model of COPD was established using LPS combined with smoking for 12 weeks

and then these COPD mice were treated with administration of 40 μL IAV

via

nasal drip to establish a AECOPD model. A total of 15 AECOPD mice were randomly divided into low-

medium- and high-dose MP groups

oseltamivir group and blank group. The body weight and survival time were monitored within 10 d after IAV infection. On days 1

and 5 post-treatment

lung function was assessed using whole-body plethysmography (WBP)

inflammatory factors in bronchoalveolar lavage fluid (BALF) were quantified with ELISA

viral titers in BALF were determined using plaque assays

and colony-forming units were evaluated with blood agar plates. Immunofluorescence analysis: ①Pulmonary immunofluorescence assay: Mice were randomly categorized into (

=4): LPS 1-day group

LPS 3-day group

and LPS+MP treatment group. All groups received an initial dose of LPS

via

atomization; subsequently

the LPS+MP treatment group received a single gavage dose of MP. Lung tissues were harvested from the 1-day LPS group on 1 d post-treatment

and from the 3-day LPS and LPS+MP groups on 3 d for immunofluorescence staining. ②Cellular immunofluorescence assay: Mouse bone marrow neutrophils were classified into blank control (no intervention)

LPS stimulation (LPS group)

MP intervention with LPS stimulation (LPS+MP group)

and MP intervention alone (MP group). The above cells were collected in 4 h after corresponding interventions for su

bsequent cellular immunofluorescence analysis. Results‍　‍①The medium-dose MP group demonstrated the most significant improvement in survival rate

weight recovery

and lung function when compared to other groups (

0.05). ② Treatment of medium-dose MP obviously reduced the levels of IL-6 and neutrophil extracellular traps (NETs) (

0.05)

while

elevated inflammatory factors and NETs were observed in the high-dose MP group on day 5 post-treatment. ③ Notable decline in the lung injury score was found in the medium-dose MP group than the other groups (

0.05). ④The high-dose MP group exhibited substantial bacterial proliferation and delayed viral clearance since day 5 after treatment. Conclusion‍　‍Medium-dose MP shows best efficacy in treatment of IAV-induced AECOPD

and the dose neither delays viral clearance nor increases the risk of bacterial infection following viral infection.

关键词

Keywords

references

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