The Relationships Of JNK/SAPK And NF-κB/IκB Signal Pathways And Lung Injury In Rats With Severe Acute Pancreatitis

Objective To investigate pathological changes,the relationship between p-JNK in JNK/SAPK signal pathways and p-IkBαin NF-rB/IkB signal pathways and severe acute pancreatitis-associated lung injury model in rats.To explore the therapeutic effect of PentoxifyllineMethods Male SD rats were divided into three groups randomly:the control group,the experimental group and the intervention group.In the control group,laparotomy were performed,duodenum and pancreas were flipped only.In the experimental group,acute necrotizing pancreatitis model was induced in rats by retrograde injection of 5%sodium taurocholate into biliopancreatic duct.In the intervention group,Pentoxifylline(50mg/kg) was injected into abdominal cavity of rats as soon as model were developed.At 2,6 and 12 hours after model were developed,The severity of pancreatitis and lung injury was determined by local pathological lesion(gross and histopathologic scoring).Serum amylase(AMY)levels,lung wet/dry ratio(W/D)were determined,too.S erum CINC,IL-6 were quantitated using ELISA kits.The protein levels of p-JNK and p-IkBαwere measured by Western Blot analysis.The effect of Pentoxifylline were observed at the same time.Results1.The lung wet/dry ratio increased at 2 hours after SAP model induction,but not higher than the control group(P＞0.05);and more at 6 and 12 hours than SAP2h(P＜0.05), higher than the control group(P＜0.05).2.Serum amylase levels increased at 2 hours after SAP model,induction,and more at 6 and 12 hours(P＜0.05);higher than the control group(P＜0.05).3.Serum CINC levels increased at 2 hours after SAP model induction,and more at 6 and 12 hours(P＜0.05);higher than the control group(P＜0.05).4.Serum IL-6 increased at 2 hours after SAP model induction,and more at 12 hours(P＜ 0.05);higher than the control group(P＜0.05).5.The expression of p-JNK in lung increased at 2 hours after SAP model induction; higher than the control group(P＜0.05).6.The expression of p-IkBαin lung increased at 2 hours after SAP model induction,and more at 12 hours(PΙ0.05);higher than the control group(P＜0.05).7.Intervention of Pentoxifylline decreased lung wet/dry ratio,Serum amylase and CINC; IL-6 in serum,p-JNK and p-IkBαin lung expression(P＜0.05);and more at 6 and 12 hours(P＜0.05).Conclusions1.Lung injury occurs at 2 hours after SAP model induction in rats,and is more severe at 6-and 12 hours.2.The expression of p-JNK in lung increased in severe acute pancreatitis-associated lung injury model in rats,and by promoting inflammatory genetic expression3.The expression of p-IkBαin lung increased obviously in severe acute pancreatitis-associated lung injury model in rats;The activity of NF-kB increased significantly that promoted inflammatory factor in excess,and it maybe cause cytokine network unbalance and cascade reaction,increase the severity of acute pancreatitis-associated lung injury.4.The intervention of Pentoxifylline may decrease pulmonary edema,CINC,IL-6 in serum,inflammatory and chemotatic factor expression,and improve Inflammatory reaction in lung,and attenuate the severity of acute pancreatitis-associated lung injury by inhibiting JNK/SAPK and NF-kB/IkB signal pathways.