脂多糖通过CCR5促进炎症细胞迁移加剧小鼠急性肺损伤

张睿昱; 雷雨溪; 刘智; 赵东赤

doi:10.14188/j.1671-8852.2025.0033

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脂多糖通过CCR5促进炎症细胞迁移加剧小鼠急性肺损伤

基础医学研究 | 更新时间：2026-11-06

- 脂多糖通过CCR5促进炎症细胞迁移加剧小鼠急性肺损伤
- Lipopolysaccharide exacerbates acute lung injury in mice by promoting the migration of inflammatory cells via the CCR5 pathway
- 武汉大学学报（医学版） 2025年46卷第12期页码：1552-1558
- 作者机构：
  
  武汉大学中南医院儿科湖北武汉 430071
- 作者简介：
  
  张睿昱，男，1994—，医学硕士生，主要从事新生儿疾病及儿童呼吸道病毒与免疫研究，E⁃mail: 252764398@qq.com
  赵东赤，男，1964—，主任医师，教授，主要从事儿童呼吸道病毒感染与免疫研究，E⁃mail: zhao_wh2004@hotmail.com
- 基金信息：
- DOI：10.14188/j.1671-8852.2025.0033
  中图分类号： R725.6
- 收稿：2025-01-08，
  
  纸质出版：2025-12-25
- 稿件说明：
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张睿昱,雷雨溪,刘智等.脂多糖通过CCR5促进炎症细胞迁移加剧小鼠急性肺损伤[J].武汉大学学报（医学版）,2025,46(12):1552-1558.

ZHANG Ruiyu,LEI Yuxi,LIU Zhi,et al.Lipopolysaccharide exacerbates acute lung injury in mice by promoting the migration of inflammatory cells via the CCR5 pathway[J].Medical Journal of Wuhan University,2025,46(12):1552-1558.
张睿昱,雷雨溪,刘智等.脂多糖通过CCR5促进炎症细胞迁移加剧小鼠急性肺损伤[J].武汉大学学报（医学版）,2025,46(12):1552-1558. DOI： 10.14188/j.1671-8852.2025.0033.

ZHANG Ruiyu,LEI Yuxi,LIU Zhi,et al.Lipopolysaccharide exacerbates acute lung injury in mice by promoting the migration of inflammatory cells via the CCR5 pathway[J].Medical Journal of Wuhan University,2025,46(12):1552-1558. DOI： 10.14188/j.1671-8852.2025.0033.

摘要

目的

探讨趋化因子受体5（CCR5）在脂多糖（LPS）诱导小鼠急性肺损伤中的作用机制。

方法

从GEO数据库下载基因集，用R软件分析CCR5及相应配体的差异表达水平。采用气管滴注LPS制备急性肺损伤小鼠模型。24 h后取材，HE染色观察肺组织病理形态并评分，计算肺组织湿重干重比；瑞氏⁃吉姆萨染色观察各组小鼠肺泡灌洗液（BALF）中炎症细胞数量，qRT⁃PCR与Western Blot法检测肺组织中CCR5 mRNA与蛋白质表达水平。构建细胞炎症模型，Western Blot法检测CCR5蛋白表达情况，体外进行划痕实验用以观察巨噬细胞的迁移能力。

结果

转录组分析(GSE18341数据集

=16)显示

LPS诱导的急性肺损伤模型中

幼年(21 d)及成年(16周)小鼠肺组织CCR5及其配体表达均显著上调(

0.05)

提示CCR5信号通路在肺损伤发病机制中的关键作用。在动物模型中，与对照组相比，LPS可引起小鼠肺损伤，肺湿/干重比明显升高，BALF中炎性细胞数目增加，肺组织中CCR5 mRNA及蛋白表达增加(

0.05)；与LPS组相比，马拉维若（Maraviroc）可缓解LPS诱导的小鼠肺组织损伤，降低肺湿/干重比，BALF中炎性细胞数量减少。体外抑制巨噬细胞CCR5可降低LPS诱导的巨噬细胞迁移。

结论

CCR5参与LPS诱导的小鼠急性肺损伤，CCR5抑制剂马拉维若可以抑制肺泡巨噬细胞迁移，减轻急性肺损伤。

Abstract

Objective

To investigate the role of CCR5 in acute lung injury (ALI) induced by lipopolysaccharide (LPS) in mice.

Methods

Gene sets were obtained from the GEO database

and the differential expression of CCR5 and its ligands was analyzed using R software. An acute lung injury model was created in mice through tracheal instillation of LPS. Afte

r 24 hours

samples were collected for HE staining to assess the pathological changes in lung tissue and to score them. The wet/dry weight ratio of lung tissue was calculated

and Wright⁃Giemsa staining was used to evaluate the number of inflammatory cells in the bronchoalveolar lavage fluid (BALF) from each group of mice. The qRT‑PCR and Western blot techniques were employed to measure the expression levels of CCR5 mRNA and protein in lung tissue. A cellular inflammation model was also developed

and Western Blot was used to assess CCR5 protein expression. Additionally

a scratch assay was performed

in vitro

to evaluate the migration ability of macrophages.

Results

Bioinformatic analysis of the GSE18341 dataset (

=16) revealed significant upregulation of CCR5 and its cognate ligands in lung tissues from both juvenile (21⁃day⁃old) and adult (16⁃week⁃old) mice following LPS⁃induced acute lung injury (

0.05). These findings demonstrated a critical role for CCR5 signaling in the pathogenesis of pulmonary injury. In our animal models

comparative analysis showed LPS exposure resulted in lung injury in mice

significantly increasing the wet/dry weight ratio and the number of inflammatory cells in BALF

along with elevated CCR5 mRNA and protein levels in lung tissue (

0.05). Treatment with Maraviroc reduced LPS⁃induced lung damage

lowered the wet/dry weight ratio

and decreased inflammatory cell counts in BALF compared with the LPS group.

In vitro

inhibiting CCR5 in macrophages diminished their migration in response to LPS.

Conclusion

CCR5 is implicated in LPS⁃induced acute lung injury in mice

and the CCR5 inhibitor Maraviroc can reduce the migration of alveolar macrophages

thereby mitigating acute lung injury.

关键词

Keywords

references

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