摘要Background:Previous studies have provided conflicting results regarding whether the serum ghrelin con-centration can reflect the severity of acute pancreatitis (AP).The present study examined the correlation between the serum ghrelin concentration and AP severity in animal models and investigated whether al-tered ghrelin expression in pancreatic acinar cells influences IKKβ/NF-κB signaling and pro-inflammatory cytokine production.Methods:Mild or severe AP was induced in rats by intraperitoneal injection of cerulein or retrograde cholangiopancreatic duct injection of sodium taurocholate,respectively.After successful model induction,serum ghrelin,tumor necrosis factor-α (TNF-α),and interleukin-6 (IL-6) concentrations were determined by enzyme-linked immunosorbent assay,and IKKβ/NF-κB activation was assessed by immunohistochem-istry.Subsequently,stable overexpression or knockdown of ghrelin in AR42J cells was achieved by lentivi-ral transfection.After transfected cells and control cells were treated with cerulein for 24 h,the TNF-α and IL-1β levels in the supernatants were determined by enzyme-linked immunosorbent assay,and the expression levels of p-p65,IKKβ,and p-IKKβ were detected by Western blotting.Results:In rat AP models,AP severity was correlated with increased IKKβ/NF-κB activation,pro-inflammatory cytokine production,and ghrelin secretion.The levels of pro-inflammatory cytokines TNF-α and IL-1β as well as IKKβ/NF-κB signaling activity were increased upon knockdown of ghrelin in the AP acinar cell model and decreased with ghrelin overexpression.Conclusions:Serum ghrelin is related to the severity of AP.Ghrelin may play a protective role in the pathogenesis of AP by inhibiting the pro-inflammatory cytokines and the activation of the IKKβ/NF-κB signaling pathway.