The Therapeutic Effect of Oxidized 1-Palmitoyl-2-Arachidonoyl-sn-Glycero-3-Phosphorylcholine in Rodents With Acute Necrotizing Pancreatitis and Its Mechanism

Abstract

This study aims to investigate the therapeutic effect of oxidized 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine (OXPAPC) in rodents with acute necrotizing pancreatitis (ANP) and its mechanism. The ANP model was induced by cerulein challenged by lipopolysaccharide in mice and taurocholic acid in Sprague-Dawley rats. Both ANP models were treated with OXPAPC. Twenty animals of each group were separated to investigate mortality. Detection included serum levels of amylase and lactate dehydrogenase, histological changes of pancreas, activity of myeloperoxidase in pancreas, mRNA expression of inflammatory factors, expression of signal transduction factor proteins, and binding activity of transcriptional factors. After treatment with OXPAPC, survival rate was improved in the rat model. In both models, OXPAPC significantly decreased serum amylase and lactate dehydrogenase levels. Histologically, OXPAPC reduced the severity of pancreatic injury. There was a significant decline of myeloperoxidase activity. The mRNA levels of intrapancreatic inflammatory factors were depressed. Activated p38, C-jun N-terminal kinase 1, and inhibitor of kappa-B kinase beta proteins were down-regulated. Electrophoretic mobility shift assay showed that the binding activity of nuclear factor-kappaB and activator protein 1 to DNA was inhibited. The OXPAPC decreased the severity of experimental ANP in rodents. The protective effect of OXPAPC was mediated, at least in part, through blocking the lipopolysaccharide signal pathway.