Mechanism of ECHS1 in ameliorating sepsis-induced pulmonary vascular endothelial barrier dysfunction

YANG Rui-bo; TAN Lei; LIU Cheng-xi; WANG Yan

doi:10.11659/jjssx.06E025055

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Mechanism of ECHS1 in ameliorating sepsis-induced pulmonary vascular endothelial barrier dysfunction

Basic Research | 更新时间：2026-05-25

- Mechanism of ECHS1 in ameliorating sepsis-induced pulmonary vascular endothelial barrier dysfunction
- JOURNAL OF REGIONAL ANATOMY AND OPERATIVE SURGERY Vol. 35, Issue 5, Pages: 401-406(2026)
- 作者机构：
  
  1.南华大学附属第二医院麻醉科，湖南衡阳 421000
  2.陆军特色医学中心麻醉科，重庆 400042
- 作者简介：
- 基金信息：
- DOI：10.11659/jjssx.06E025055
  CLC： R563;R631
- Received：12 June 2025，
  
  Published：25 May 2026
- 稿件说明：
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杨瑞博,谭磊,刘程曦等.ECHS1改善脓毒症肺血管内皮屏障功能障碍的机制研究[J].局解手术学杂志,2026,35(05):401-406.

YANG Rui-bo,TAN Lei,LIU Cheng-xi,et al.Mechanism of ECHS1 in ameliorating sepsis-induced pulmonary vascular endothelial barrier dysfunction[J].JOURNAL OF REGIONAL ANATOMY AND OPERATIVE SURGERY,2026,35(05):401-406.
杨瑞博,谭磊,刘程曦等.ECHS1改善脓毒症肺血管内皮屏障功能障碍的机制研究[J].局解手术学杂志,2026,35(05):401-406. DOI： 10.11659/jjssx.06E025055.

YANG Rui-bo,TAN Lei,LIU Cheng-xi,et al.Mechanism of ECHS1 in ameliorating sepsis-induced pulmonary vascular endothelial barrier dysfunction[J].JOURNAL OF REGIONAL ANATOMY AND OPERATIVE SURGERY,2026,35(05):401-406. DOI： 10.11659/jjssx.06E025055.

摘要

目的

探究短链烯酰辅酶A水合酶1（ECHS1）在脓毒症肺血管内皮屏障功能障碍中的作用及潜在机制。

方法

在动物水平将成年SD大鼠随机分为假手术（Sham）组、脓毒症（Sepsis）组和ECHS1敲低（AAV-shECHS1）组。Sham组大鼠仅开关腹，Sepsis组大鼠行盲肠结扎穿孔术构建脓毒症模型，AAV-shECHS1组大鼠于建模前4周经尾静脉注射ECHS1敲低腺相关病毒。Western blot检测ECHS1蛋白表达。在建模12 h后观察各组大鼠存活情况；取各组大鼠肺组织行HE染色，评估大鼠肺组织损伤；进行血管通透性测定。细胞水平培养原代肺静脉内皮细胞（VECs），通过脂多糖（LPS）刺激模拟脓毒症模型，利用腺病毒敲低ECHS1，测定VECs的电阻率、ECHS1表达及赖氨酸巴豆酰化（Kcr）修饰水平，经转录组学分析获得关键差异基因。

结果

脓毒症大鼠出现肺损伤及肺血管内皮屏障功能障碍，表现为肺组织结构破坏和肺VECs通透性增加；大鼠存活率显著下降，生存时间缩短，同时伴肺VECs的Kcr修饰水平显著降低，ECHS1表达显著升高。敲低ECHS1可有效上调脓毒症VECs的Kcr修饰水平，改善肺血管内皮屏障功能和肺损伤，显著提高大鼠存活率，延长生存时间。

结论

敲低ECHS1可上调VECs的Kcr水平，从而改善脓毒症大鼠血管内皮屏障功能。

Abstract

Objective

To investigate the role and underlying mechanism of short-chain enoyl-CoA hydratase 1 （ECHS1） in sepsis-induced pulmonary vascular endothelial barrier dysfunction.

Methods

Adult SD rats were randomly divided into the Sham group，Sepsis group，and ECHS1 knockdown （AAV-shECHS1） group. Rats in the Sham group underwent only laparotomy，while rats in the Sepsis group underwent cecal ligation and puncture to construct a sepsis model， and rats in the AAV-shECHS1 group were injected with ECHS1-knockdown adeno-associated virus via the tail vein 4 weeks before modeling. The expression of ECHS1 protein was detected by Western blot. The survival of rats in each group was observed 12 hours after modeling； the lung tissues of rats in each group were collected for HE staining to evaluate lung tissue injury， and vascular permeability was determined. Primary pulmonary vascular endothelial cells （VECs） were cultured and stimulated with lipopolysaccharide （LPS） to simulate the sepsis model， and ECHS1 was knocked down in cells using adenovirus. The electrical resistance of VECs， the expression of ECHS1， and the levels of lysine crotonylation （Kcr） were detected， and transcriptomic analysis was then performed to identify key differentially expressed genes.

Results

Septic rats developed lung injury and pulmonary vascular endothelial barrier dysfunction， characterized by destruction of lung tissue structure and increased permeability of pulmonary VECs； in addition， the survival rate of the rats was significantly decreased， along with shortened survival time. Meanwhile， the Kcr modification level in pulmonary VECs was significantly reduced， while the expression of ECHS1 was significantly increased. Knockdown of ECHS1 effectively upregulated the Kcr modification level in septic VECs， improved pulmonary vascular endothelial barrier function and lung injury， significantly increased the survival rate， and prolonged the survival time of septic rats.

Conclusion

Knockdown of ECHS1 upregulates Kcr levels in VECs， thereby improving vascular endothelial barrier function in septic rats.

关键词

Keywords

references

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