Intestinal Mucus Layer Mediates Intestinal Damage During Acute Necrotizing Pancreatitis In Rats

Background and Objective:Lots of studies have shown that acute necrotizing pancreatitis(ANP)can lead to increased intestinal permeability and intestinal endotoxemia in the early stage.These involve the occurrence of intestinal barrier dysfunction.The mechanisms of increased intestinal permeability have yet to be fully elucidated.The intestinal mucus layer is secreted by goblet cells,the most important component is Mucin-2(MUC2).It can isolate pathogens from intestinal epithelial cells and maintain the normal function of the intestinal barrier.However,the role of intestinal mucus layer in the intestinal barrier of ANP has not been reported so far.The aim of the present study was to investigate the changes of intestinal mucus layer in rats with ANP and the injury of intestine and pancreas after intestinal mucus depletion by pilocarpine in ANP.Methods:Rats with ANP were established by retrograde injection of 3.5% sodium taurocholate into biliopancreatic duct.A model of mucus-depleting was established by intraperitoneal injection of pilocarpine(160mg/kg).Pancreatic injury was evaluated by serum amylase level and histopathological score.Intestinal barrier injury was determined by measuring serum D-lactate level and histopathology.The dynamic changes of intestinal MUC2,inflammatory cytokines TNF-a,IL-1β and IFN-γ mRNA were detected by real-time PCR.The changes of colonic mucus layer and goblet cells were observed by Periodic Acid Schiff / Alcian Blue staining(PAS/AB).Results:Compared with the normal sham-operated(SO)group,the ANP group of rats had more severe histopathological injuries in pancreas and distal colon,increased intestinal permeability and up-regulated TNF-a,IL-1β and IFN-γ mRNAs in the distal colonic tissue(p<0.05).At the same time,intestinal mucus layer was thinner,mucus-containing goblet cells and MUC2 mRNA expression significantly decreased.MUC2 mRNA expression was negatively correlated with the intestinal permeability and expression of inflammatory cytokines mRNAs in the ANP group by Spearman correlation coefficient.Compared with the ANP group,intestinal mucus deficiency,goblet cell depletion,intestinal pathology and inflammatory reaction were significantly increased in the pilocarpine+ANP group.At the same time,pancreatic pathology was aggravated and serum amylase was significantly increased.Conclusion:Increased intestinal permeability and intestine damage were observed in ANP with destroyed intestinal mucus layer and decreased MUC2 expression.Decreased intestinal mucus secretion may be involved in intestinal barrier injury during ANP.