Establishment Of The Rat Model Of Severe Acute Pancreatitis SIRS And The Change Of Phagocytotic Ability Of It's Peritoneal Macrophage

Background:Systemic inflammatory response syndrome(SIRS) is a new term which was proposed in the conference of ACCP and SCCM in aug,1991.Macrophage(MΦ) and polymorphonuclear neutrophil(PMN) are two main effector cells in the process of inflammation.Clearance of apoptotic neutrophils by macrophages is thought to play a crucial role in resolution of acute inflammation.If apoptotic neutriphils are not cleared promptly and efficiently by macrophages because of dysfunction of phagocytosis and go to rupture, they will release many cytotoxic contents and inflammatory mediators.Finally,the inflammation will be out of control. Hietaranta et al reported that early systemic complications of severe acute pancreatitis(SAP) were associated with the increasing frequency of SIRS.There are many reports about the relationship between SAP and SIRS both at home and abroad,but few of experimental studies about it are reported.There is no standard animal model of SIRS and it is still on the stage of exploration.Objectives:To establish the rat model of severe acute pancreatitis SIRS by detecting relative indexes of each SAP group according to Husen's diagnosis for animal SIRS and detect the change of phagocytotic ability of it's peritoneal macrophage(pMΦ) and observe the effects of medicine on it.Methods:60 healthy male Sprague-Dawley rats were selected from the experimental animal center of Dalian medical university,with weight from 180g to 220g.On the stage of establishment of the rat model of severe acute pancreatitis SIRS:30 rats were randomly divided into 3 groups(sham operation group,SAP 12 hours group,and SAP 24 hours group);On the stage of detecting the phagocytotic ability of pMΦ:30 rats were randomly divided into 3 groups(sham operation group, severe acute pancreatitis SIRS model group,and dexamethasone treatment group).The SAP model was induced by retrograde infusion of 1.5% sodium deoxycholate into biliopancreatic duct of rats. Then relative indexes(rectal temperature,WBC, PaCO₂,PaO₂,serum mediators of inflammation, plasm endotoxin,and pathological alteration of main organs) are detected according to Husen's diagnosis for animal SIRS and compared with sham operation group's to confirm which SAP group fit the criteria of SIRS.Then use it as the model of severe acute pancreatitis SIRS. pMΦs were collected from rats by peritoneal lavage method and PMNs were segregated from rats'blood by dextran gradient centrifugation method.The phagocytotic ability that macrophage of SIRS model group phagocytize apoptotic PMN was detected and compared with sham operation group and medicine group.Results:(1)Model confirmation:1)Rectal temperature:compared with sham operation group, rectal temperature of SAP 12h group decreased 0.5℃averagely.The difference is significant(P<0.05); rectal temperature of SAP 24h group increased 1.0±0.2℃averagely.The difference is very significant(P<0.01).2)WBC:compared with sham operation group,WBC of SAP 12h group increased markedly(P < 0.05);WBC of SAP 24h group increased very markedly(P<0.01) and exceed over 2 times for control.3) PaCO₂:compared with sham operation group, there is a significant decrease in SAP 12h group(P<0.01),and a significant increase in SAP 24h group(P<0.01);PaO₂: SAP 12h group has a significant increase(P<0.01),SAP 24h group has a significant decrease(P<0.01).4)TNF-α,IL-6 and endotoxin: compared with sham operation group,SAP 12h and SAP 24h groups all have a significant increase(P<0.01).5)organs pathology:SAP 12h group and SAP 24h group all have a significant inflammatory alteration in main organs(pancrea, liver, lung, kidney).(2)phagocytotic ability of pMΦ:1)compared with sham operation group,severe acute pancreatitis SIRS group have a significant decrease on phagocytosis rate and index(P<0.01).2)After treatment with dexamethasone, phagocytosis rate and index of pMΦhave a significant increase(P<0.01).Conclusion:(1)It is confirmed that relative indexes of the SAP model which was induced by retrograde infusion of 1.5% sodium deoxycholate into biliopancreatic duct of rats after 24 hours reach to the criteria of SIRS.Thus,the rat model of SAP can be recognized as a carrier of SIRS.(2)The decrease of phagocytotic ability of pMΦmaybe play a certain role in the process of promoting SIRS in the rat model of severe acute pancreatitis SIRS.(3)Dexamethasone can promote peritoneal macrophages of severe acute pancreatitis SIRS to phagocytize apoptotic neutrophils.