Antithrombin Ⅲ reduces sepsis⁃induced acute lung injury by reducing alveolar barrier permeability

LI Dongxu; SONG Zhenju; WANG Lu; YU Bing; DAI Qingqing

doi:10.14188/j.1671-8852.2024.0496

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Antithrombin Ⅲ reduces sepsis⁃induced acute lung injury by reducing alveolar barrier permeability

更新时间：2026-11-05

- Antithrombin Ⅲ reduces sepsis⁃induced acute lung injury by reducing alveolar barrier permeability
- Medical Journal of Wuhan University Vol. 46, Issue 2, Pages: 153-159(2025)
- 作者机构：
  
  1.复旦大学附属妇产科医院重症医学科上海 200082
  2.复旦大学附属中山医院急诊科/复旦大学应急救援与急危重症研究所上海 200032
  3.武汉大学人民医院重症医学科湖北武汉 430060
  4.中国人民解放军海军军医大学细胞生物学教研室上海 200433
- 作者简介：
- 基金信息：
- DOI：10.14188/j.1671-8852.2024.0496
  CLC： R56
- Received：10 September 2024，
  
  Published：25 February 2025
- 稿件说明：
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李东旭,宋振举,王璐等.抗凝血酶Ⅲ通过降低肺泡屏障通透性减轻脓毒症急性肺损伤[J].武汉大学学报（医学版）,2025,46(02):153-159.

LI Dongxu,SONG Zhenju,WANG Lu,et al.Antithrombin Ⅲ reduces sepsis⁃induced acute lung injury by reducing alveolar barrier permeability[J].Medical Journal of Wuhan University,2025,46(02):153-159.
李东旭,宋振举,王璐等.抗凝血酶Ⅲ通过降低肺泡屏障通透性减轻脓毒症急性肺损伤[J].武汉大学学报（医学版）,2025,46(02):153-159. DOI： 10.14188/j.1671-8852.2024.0496.

LI Dongxu,SONG Zhenju,WANG Lu,et al.Antithrombin Ⅲ reduces sepsis⁃induced acute lung injury by reducing alveolar barrier permeability[J].Medical Journal of Wuhan University,2025,46(02):153-159. DOI： 10.14188/j.1671-8852.2024.0496.

摘要

目的

探讨抗凝血酶Ⅲ(ATⅢ)对脓毒症急性肺损伤肺泡屏障的保护作用。

方法

将雄性C57BL/6J小鼠随机分成3组，①脓毒症组（LPS组）：将小鼠饥饿16 h后，腹腔注射20 mg/kg 脂多糖（LPS）；②脓毒症+ATⅢ组（LPS+ATⅢ组）：LPS注射2 h后，尾静脉注射750 IU/kg ATⅢ；③对照组（Control组）：参照LPS和ATⅢ的给药途径与时间分别注射等体积生理盐水。在ATⅢ给药24 h后收集血清、肺泡灌洗液以及肺组织等标本，采用HE染色结合肺损伤评分评价肺组织的形态结构与损伤程度；采用肺湿/干重比（W/D）、肺泡灌洗液（BALF）中的细胞数量与蛋白量以及FITC⁃Dextran渗透实验测量肺泡屏障通透性；采用免疫组织学染色检测肺组织细胞间紧密连接组成蛋白的表达量。

结果

LPS组的肺损伤评分、肺湿/干重比（W/D值）、肺泡屏障通透性均较Control组显著升高（

0.01），细胞间紧密连接的组成蛋白ZO⁃1、Occludin和Claudin3的表达水平均显著降低（

0.001）。而LPS+ATⅢ组的肺损伤评分、W/D值、肺泡屏障通透性较LPS组均降低（

0.05），ZO⁃1、Occludin和Claudin3表达水平升高（

0.01）。

结论

ATⅢ增加细胞间紧密连接组成蛋白的表达

进而降低肺泡屏障的通透性，从而减轻脓毒症急性肺损伤。

Abstract

Objective

To explore the protective effect of antithrombin Ⅲ (ATⅢ) on the alveolar barrier in acute lung injury induced by sepsis.

Methods

Male C57BL/6J mice were randomly divided into three groups

①sepsis group (LPS group): after fasting the mice for 16 hours

20 mg/kg lipopolysaccharide (LPS) was injected intraperitoneally; ②sepsis treated with ATⅢ group (LPS+ATⅢ group): 750 IU/kg ATⅢ was injected via the tail vein 2 hours after LPS injection; ③control group: equal volume of saline were injected according to the strategies of the administration of LPS and ATⅢ. The serum

bronchoalveolar lavage fluid (BALF)

and lung tissue samples were collected 24 hours after ATⅢ administration. HE staining combined with lung injury scoring was used to assess the morphological structure and degree of damage in lung tissues; the lung wet/dry weight ratio (W/D)

cell count and protein content in BALF

and FITC⁃Dextran permeability assay were employed to measure pulmonary barrier permeability; immunohistochemical staining was utilized to detect the expression levels of tight junction proteins in lung tissues.

Results

The lung injury score

lung W/D value and the permeability of the alveolar barrier in the LPS group were significantly increased as compared with those in the control group (

0.01); the expression levels of the components of tight junctions

ZO⁃1

occludin

and Claudin3 were significantly reduced (

0.001). However

the lung injury score

W/D value

and the permeability of the alveolar barrier in the LPS+ATⅢ group were lower than those in the LPS group (

0.05)

and the expression level of ZO⁃1

occludin

and Claudin3 was higher (

0.01).

Conclusion

ATⅢ reduces the permeability of the alveolar barrier by increasing the expression of tight junction proteins

thus alleviating acute lung injury induced by sepsis.

关键词

Keywords

references

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Related Institution

Dept. of Critical Care Medicine， The Obstetrics & Gynecology Hospital of Fudan University

Dept. of Emergency， Zhongshan Hospital Fudan University & Institute of Emergency Rescue and Critical Care， Fudan University

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Dept. of Cell Biology， Naval Medical University

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