Objective:To investigate the role of nuclear factor κB（NF-κB）in impairment of esophageal barrier function viagastroesophageal reflux（GER） and to provide theoretical guidance for treatment. Methods:Surgical models of duodenal and mixed re flux were developed in mice. Trans-epithelial electrical resistance（TEER）and intercellular space of esophageal mucosa were detected by mini-Ussing chamber and Toluidine Blue stain.Mouse esophageal epithelium was analyzed by gene micro-array. The expressions of NF-κB subunits（p50 and p65） and tight junction proteins（Cldn1 and Cldn4） were detected by immunohistochemistry. Cldn1 and Cldn4 were also quantified by qRT-PCR and Western blot. NF-κB target genes（IL-1β

IL-6 and IL-8）were detected by ELISA.Neutrophils

mast cells and eosinophils within mucosa were quantified. The duodenal and mixed reflux models were treated with an NF-κB inhibitor

Bay11-7085 [20 mg/（kg·d） i.p.] for 10 days. The TEER and cytokines（IL-1β

IL-6

IL-8） were measured.Results:Decrease of TEER and dilated intercellular space were observed in mucosa via reflux.Activation of NF-κB pathway was confirmed by gene set enrichment analysis and significance analysis of micro-arrays. Cldn1 and Cldn4 were down-regulated and mislocalized by qRT-PCR

Western blot and immunohistochemistry.Increase of neutrophils

mast cells and eosinophils within refluxed mucosa were observed. Treatment with Bay11-7085 counteracted the effect of reflux on TEER and cytokines. Conclusion:GER activates NF-κB pathway and attenuates esophageal barrier function in mice. Targeting NF-κB pathway is a potential way to strengthen esophageal barrier function.