局解手术学杂志2026，Vol.35Issue(5)：401-407,7.DOI:10.11659/jjssx.06E025055
ECHS1改善脓毒症肺血管内皮屏障功能障碍的机制研究
Mechanism of ECHS1 in ameliorating sepsis-induced pulmonary vascular endothelial barrier dysfunction
摘要
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-knock-down 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
脓毒症/大鼠/血管内皮屏障功能/巴豆酰化/短链烯酰辅酶A水合酶1Key words
sepsis/rats/vascular endothelial barrier function/lysine crotonylation/short-chain enoyl-CoA hydratase 1分类
医药卫生引用本文复制引用
杨瑞博,谭磊,刘程曦,王燕..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(5):401-407,7.基金项目
国家自然科学基金(82300561) （82300561）
重庆市科卫联合青年项目(2025QNXM038) （2025QNXM038）
陆军军医大学科技创新能力提升专项项目(2023XLC11) （2023XLC11）
