| Objective:1、establish a mouse model of severe acute pancreatitis, observe the change of thecourse of pancreatitis in mice.2、to observe the effect of lipoxin A4in mice with severe acute pancreatitis and lunginjury, renal injury, and to explore its mechanism.Methods：1、 By retrograde pancreatic duct injection of low concentration of bile salt inducedby severe acute pancreatitis model in mice, the mice were divided into two groups,SAP group and sham operation group, SAP group mice retrograde pancreatic ductinjection of2%sodium taurocholate50microliter, and the operation group micereceived laparotomy only turning tube, after12h,24h,48h the mouse were killedto evaluate the severity of acute pancreatitis.2、30male ICR mice, weighing about20-25g, were randomly divided into SAPgroup, control group and LXA4treatment group, with10mouse in each group,Severe acute pancreatitis were induced by by retrograde pancreatic duct injectionof2%sodium taurocholate solution, Sham operation group was turning theintestine.The mouse of LXA4treatment group tail vein injection of LXA40.1mg/kg after operation, Sham operation group and SAP group were injectedwith normal saline.24hours after the operation the mice were killed to collectblood samples, and pancreas, kidney, lung and other tissues, serum TNF-α andIL-10were detected by ELISA, Detected the serum creatinine, urea nitrogen level,observed the mice pancreas, lung, kidney pathological changes and scored,colorimetric detection of pancreas, kidney, lung MPO activity, MDA content in lung tissue was detected by TBA, determination of lung and pancreatic wet to dryweight ratio，the expression of NF-κ B p65in nuclear、I κ B α in cytoplasmic ofpancreas、renal and lung tissue were evaluated by Western Blot.3、 Result：1、SAP mice serum amylase, pancreatic tissue pathological score, pancreatic tissuewater content were significantly higher than those in the sham operationgroup(P<0.05), SAP group were24h and48hours of pancreatic tissue pathologicalscore, pancreatic tissue water content was significantly higher than that of12h(P<0.05), but between24h and48h group had no significant difference(P>0.05).2、SAP mice serum TNF-α、IL-10、 CR、 BUN，pancreas、 lung and kidney tissueMPO activity, the expression of NF-κ B p65, the content of MDA of lung and lungwet to dry weight ratio were higher than the sham operation group(P<0.05), theexpression of pancreas, lung and kidney tissues of I κ B α is lower than that of thesham operation group(P<0.05), and histopathological examination showed that thepancreas、 lung and kidney has different degrees of injury, pathological scores werehigher than those in the sham operation group. In LXA4treatment group, serum TNF-α、CR、BUN, pancreas、lung and kidney tissue MPO activity, the expression of NF-κ B p65, the content of MDA of lung and lung wet to dry weight ratio compared withthe SAP group decreased(P<0.05), serum IL-10and tissue I κ B α expression rise, andpathology revealed pancreatic、lung and kidney tissue damage reduction light,pathological score also declined(P<0.05).Conclusion：1、Success by retrograde pancreatic duct injection of2%sodium taurocholate toestablish the mouse model of severe acute pancreatitis, and24hours after operationpancreatitis pathological damage was most.2、LXA4has a protective effecting on mice with severe acute pancreatitis andassociated lung injury, renal injury, and its mechanism might be through down-regulation of express of NF-κ B, regulation of pro and anti-inflammatorybalance to complete... |
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