Mechanism of HMOX1 Alleviating Sepsis-Induced Acute Lung Injury by Blocking the NF-κB/STAT3 Signaling Pathway

ZHANG Hongmei; QIAN Kejian

doi:10.13919/j.issn.2095-6274.ZHJY202505054

Abstract：Objective To investigate the mechanism of heme oxygenase-1(HMOX1)in sepsis-induced acute lung injury(SIALI)by regulating the NF-κB/STAT3 signaling pathway.Methods An animal model of ALI was established using cecal ligation and puncture(CLP),and an in vitro model was constructed by stimulating hu-man pulmonary artery endothelial cells(HPAECs)with lipopolysaccharide(LPS).HMOX1 expression was detect-ed by quantitative real-time PCR(qRT-PCR).Protein expression was measured by Western blotting.Pathological changes in lung tissue were analyzed by hematoxylin-eosin(HE)and Masson staining.The expression of Ki-67 and HMOX1 was detected by immunohistochemistry.Inflammatory cytokine levels were measured by enzyme-linked immunosorbent assay(ELISA).Cell apoptosis was assessed by TUNEL assay.Results HMOX1 was highly ex-pressed in the serum of ALI patients,lung tissues of model rats,and LPS-stimulated HPAECs.Overexpression of HMOX1 significantly ameliorated lung tissue injury,reduced inflammatory cytokine levels and the apoptosis rate,and inhibited the phosphorylation-mediated activation of the NF-κB/STAT3 signaling pathway.Conversely,the NF-κB inhibitor BAY 11-7082 partially reversed the protective effects of HMOX1.Conclusion HMOX1 effectively ameliorates ALI by blocking the activation of the NF-κB/STAT3 signaling pathway.This study provides experimen-tal evidence for targeting HMOX1 as a potential therapeutic strategy for SIALI.