Role of extracellular DNA in inflammatory injury of acute respiratory distress syndrome mice

Yao LU; Lingfeng WANG; Han ZHANG; Wenjun XIA; Guixiang SUN; Aiqing WEN

doi:10.16016/j.1000-5404.201712077

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Role of extracellular DNA in inflammatory injury of acute respiratory distress syndrome mice

Basic Medicine | 更新时间：2026-01-09

- Role of extracellular DNA in inflammatory injury of acute respiratory distress syndrome mice
- Journal of Third Military Medical University Vol. 40, Issue 13, Pages: 1166-1170(2018)
- 作者机构：
  
  400042 重庆，陆军军医大学(第三军医大学)第三附属医院(野战外科研究所)输血科
- 作者简介：
- 基金信息：
  
  the General Program of National Natural Science Foundation of China(81770195)
- DOI：10.16016/j.1000-5404.201712077
  CLC： R364.5;R392.3;R563.8
- Received：07 December 2017，
  
  Revised：2018-01-19，
  
  Published：15 July 2018
- 稿件说明：
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Yao LU, Lingfeng WANG, Han ZHANG, et al. Role of extracellular DNA in inflammatory injury of acute respiratory distress syndrome mice[J]. Journal of Third Military Medical University, 2018, 40(13): 1166-1170.
DOI：

Yao LU, Lingfeng WANG, Han ZHANG, et al. Role of extracellular DNA in inflammatory injury of acute respiratory distress syndrome mice[J]. Journal of Third Military Medical University, 2018, 40(13): 1166-1170. DOI： 10.16016/j.1000-5404.201712077.

摘要

目的

研究脂多糖(lipopolysaccharide

LPS)诱导急性呼吸窘迫综合征(acute respiratory distress syndrome，ARDS)小鼠胞外DNA的生成情况及其对肺部炎症损伤的作用。

方法

以LPS(6 mg/kg)经鼻气管滴注法建立ARDS模型。40只雄性C57BL/6小鼠按随机数字表法分为对照组、DNaseⅠ组、LPS组和LPS+DNaseⅠ组，每组10只。造模后24 h取肺组织行HE染色观察肺组织病理改变；取支气管肺泡灌洗液(bronchoalveolar lavage fluid

BALF)检测细胞数量，采用超敏荧光核酸染料检测其中双链DNA浓度；采用ELISA检测BALF中白介素-6(interleukin 6

IL-6)、肿瘤坏死因子α(tumor necrosis factor α

TNF-α)和髓过氧化物酶(myeloperoxidase

MPO)浓度。

结果

LPS组小鼠肺组织HE染色可见大量中性粒细胞浸润、肺泡结构破坏、肺泡出血及间质水肿，提示LPS诱导ARDS建模成功。LPS组BALF中细胞计数、MPO、IL-6、TNF-α和双链DNA浓度均分别显著高于对照组(

＜0.05)，LPS+DNaseⅠ组肺损伤评分和炎症指标均较LPS组显著降低(

＜0.05)。

结论

LPS诱导ARDS小鼠BALF中胞外DNA浓度升高，而DNaseⅠ能够降低ARDS小鼠BALF中DNA浓度，减轻肺部炎症损伤。

Abstract

Objective

To investigate the production of extracellular DNA and its role in inflammatory injury in lipopolysaccharide (LPS)-induced mouse model of acute respiratory distress syndrome (ARDS).

Methods

Forty male C57BL/6 mice were randomly divided into 4 groups

that is

control group

deoxyribonuclease Ⅰ (DNaseⅠ) group

LPS group and LPS+DNaseⅠ group

with 10 animals in each group. ARDS was induced by intranasal instillation of LPS (6 mg/kg). In 24 h later

lung lobes were collected and stained with HE for histopathological observation

and bronchoalveolar lavage fluid (BALF) were harvested for total cell count by hemocytometry and double-stranded DNA content by a reagent containing ultrasensitive fluorescent nucleic acid stain. The concentrations of IL-6

TNF-α and myeloperoxidase (MPO) were determined using ELISA.

Results

Histopathological analysis showed that LPS treatment resulted in massive infiltration of neutrophils

destruction of alveolar structure of lungs

alveolar hemorrhage and interstitial edema

suggesting the successful establishment of the model. The total cell counts and concentrations of MPO

IL-6

TNF-α and double-stranded DNA in the BALF were significantly higher in the LPS group than the control group (

0.05). DNaseⅠ treatment significantly reduced the lung injury score and inflammatory indicators when compared with the model group (

0.05).

Conclusion

BALF extracellular DNA level is increased in LPS-induced ARDS mice

and DNaseⅠ treatment can neutralize the DNA level in the BALF and thus attenuate lung injury and inflammation.

关键词

Keywords

references

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