ECHS1改善脓毒症肺血管内皮屏障功能障碍的机制研究OA

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.