HIF-1α Enhances Intestinal Injury and Inflammation in Severe Acute Pancreatitis Through NLRP3 Inflammasome Activation

BackgroundSevere Acute Pancreatitis (SAP) is associated with significant intestinal injury and inflammation. Hypoxia-Inducible Factor-1 alpha (HIF-1 alpha) and NLRP3 inflammasome have been implicated in this process, but their specific roles remain unclear.ObjectiveThis study aims to elucidate the roles of HIF-1 alpha and NLRP3 in the pathogenesis of SAP and their effects on intestinal injury, barrier function, and inflammatory responses.MethodsA SAP rat model was established, and histological changes were assessed via HE staining. Western blot was used to analyze HIF-1 alpha and NLRP3 expression in intestinal mucosa. The effects of HIF-1 alpha modulation were examined using the activator DMOG and inhibitor BAY87-2243. Immunohistochemistry, ELISA, and TUNEL staining were used to evaluate intestinal barrier function, permeability markers, and apoptosis.ResultsHIF-1 alpha and NLRP3 expression significantly increased in SAP rats, peaking at 72 h. HIF-1 alpha activation aggravated intestinal injury and barrier dysfunction, decreasing tight junction protein levels and increasing epithelial apoptosis. Enhanced intestinal permeability and elevated pro-inflammatory cytokines were also observed. Furthermore, HIF-1 alpha activation promoted NLRP3 inflammasome assembly, resulting in increased caspase-1 and IL-1 beta expression.ConclusionHIF-1 alpha exacerbates intestinal injury and inflammation in SAP, likely through NLRP3 inflammasome activation. Targeting HIF-1 alpha may offer a potential therapeutic approach for SAP-induced damage and inflammation.