Objective To investigate the relationship between NF-κB activation,cytokines release and acute necrotizing pancreatitis in the rats,and to assess the effectiveness of pyrrolidine dithiocarbamate(PDTC),an inhibitor of NF-κB,on the experimental acute necrotizing pancreatitis Methods SD rats were randomly divided into three group:normal group(Z group),pancreatitis group(Y group),per-intervention group with PDTC,1 hour before modeling(A group),post-intervention group 1 hour after modeling(B group),and(C group) group-treated with PDTC 6 hours after modeling.Each group were randomly sub-divided into 6,12,24 h group repectively.Acute necrotizing pancreatitis rat model was produced by injecting taurocholate into the biliopancreatic duct.PDTC was injected intraperitoneally.Each group were sacrificed at 6,12 or 24 h after modeling.The activity of NF-κB in pancreas was examined by gel electrophoretic mobility shift assays(EMSA).The serum levels of IL-6,-8,-10 and TNF-α were measurred by enzyme linked immunosorbent assay(ELSA).The level of amylase was deteced by clinical biochemical auto machine.Results NF-κB binding activity was not detected in Z group.Compared with Z group,activity of NF-κB in liver,lung and pancreas was significantly higher at 6 to 24 h(P<0.001),meanwhile,serum IL-6,-8,-10 and TNFα of Y group increased sharply(P<0.001 vs Z group).PDTC inhibited the activity of NF-κB effectively.NFκB binding activity in group A was much more inhibited compared with group Y or B.Meanwhile the serum levels of IL-6,-8,-10 and TNF-α in group A were much lower than those in group Y.Moreover,NF-κB binding activity and serum levels of IL-6,-8,-10,TNF-α in C group were not inhitibed compared with group Y.Amylase elevated distinctly in the group Y.But there were no valuable changes occurred among group A,B,C and Y.There was a close relationship between NF-κB and those cytokines.The phlogistic changes in the pancreas could be observed in group Y.After intervention with PCTC,the pathological changes were significantly alleviated in group A.Conclusions There is an evident relation between NF-κB and acute necrotizing pancreatitis.In severe acute pancreatitis,NF-κB play a vital role in the course of acute necrotizing pancreatitis through controlling the expression of cytokines.Inhibiting NF-κB binding activity can depress those cytokines mentioned above.Early blockage of NF-κB may prevent multiple organ failure in acute necrotizing pancreatitis. |