AIM TO establish a non-traumatic,easy to induce andreproducible mouse model of severe acute pancreatitis(SAP)induced with caerulein and lipopolyasccharide(LPS).METHODS:Thirty-two healthy mature NIH female micewere selected and divided at random into four groups(eachof 8 mice),i.e.,the control group(NS group),the caeruleingroup(Cn group),the lipopolysaccharide group(LPS group),and the caerulein+LPS group(Cn+LPS group).Mice wereinjected intraperitoneally with caerulein only,or LPS only,and caerulein and LPS in combination.All the animals werethen killed by neck dislocation three hours after the lastintraperitoneal injection.The pancreas and exo-pancreaticorgans were then carefully removed for microscopicexamination.And the pancreatic acinus was further observedunder transmission electron microscope(TEM).Pancreaticweight,serum amylase,serum nitric oxide(NO)concentration,superoxide dismutase(SOD)andmalondialdehyde(MDA)concentration of the pancreas wereassayed respectively.RESULTS:(1)NS animals displayed normal pancreaticstructure both in the exocrine and endocrine.In the LPSgroup,the pancreas was slightly edematous,with theinfiltration of a few inflammatory cells and the necrosis ofthe adjacent fat tissues.All the animals of the Cn groupshowed distinct signs of a mild edematous pancreatitischaracterized by interstitial edema,infiltration of neutrophiland mononuclear cells,but without obvious parenchymanecrosis and hemorrhage.In contrast,the Cn+LPS groupshowed more diffuse focal areas of nonviable pancreaticand hemorrhage as well as systemic organ dysfunction.According to Schmidt’s criteria,the pancreatic histologic scoreshowed that there existed significant difference in the Cn+LPSgroup in the interstitial edema,inflammatory infiltration,parenchyma necrosis and parenchyma homorrhage incomparison with those of the Cn group,LPS group and NSgroup(P<0.01 or P<0.05).(2)The ultrasturcture of acinarcells was seriously damaged in the Cn+LPS group.Chromatinmargination of nuclei was present,the number and volumeof vacuoles greatly increased.Zymogen granules(ZGs)weregreatly decreased in number and endoplasmic reticulumexhibited whorls.The swollen mitochondria appeared,thecrista of which was decreased in number or disappeared.(3)Pancreatic weight and serum amylase levels in the Cn +LPS was significantly higher than those of the NS groupand the LPS group respectively(P<0.01 or P<0.05).However,the pancreatic wet weight and serum amylaseconcentration showed no significant difference between theCn+LPS group and the Cn group.(4)NO concentration inthe Cn+LPS group was significantly higher than that of NSgroup,LP5 group and Cn group(P<0.05 or P<0.01).5)TheSOD and MDA concentration of the pancreas in the Cn+LPSgroup were significantly higher than those of NS,LPS andCn groups(P<0.05 or P<0.01).CONCLUSION:The mouse model of severe acutepancreatitis could be induced with caerulein and LPS,whichcould be non-traumatic and easy to induce,reproduciblewith the same pathological characteristics as those of SAPin human,and could be used in the research on the mechanismof human SAP. AIM TO establish a non-traumatic, easy to induce andreproducible mouse model of severe acute pancreatitis (SAP) induced with caerulein and lipopolyasccharide (LPS) .METHODS: Thirty-two healthy mature NIH female micewere selected and divided at random into four groups (eachof 8 mice), ie, the control group (NS group), the caeruleingroup (Cn group), the lipopolysaccharide group (LPS group), and the caerulein + LPS group (Cn + LPS group) .Mice were injected intraperitoneally with caerulein only, or LPS only, and caerulein and LPS in combination. All the animals were killed by neck dislocation three hours after the last intraperitoneal injection. The pancreas and exo-pancreaticorgans were then carefully removed for microscopicexamination. And the pancreatic acinus was further observed under transmission electron microscope (TEM ) .Pancreaticweight, serum amylase, serum nitric oxide (NO) concentration, superoxide dismutase (SOD) andmalondialdehyde (MDA) concentration of the pancreas were all assayed respectively.RESULTS: (1) NS ani mals displayed normal pancreaticstructure both in the exocrine and endocrine.In the LPSgroup, the pancreas was slightly edematous, with theinfiltration of a few inflammatory cells and the necrosis ofthe adjacent fat tissues. All the animals of the Cn group show distinct signs of a mild edematous pancreatitis characterized by interstitial edema, infiltration of neutrophiland mononuclear cells, but without obvious parenchymanecrosis and hemorrhage. contrast, the Cn + LPS group shove more diffuse focal areas of nonviable pancreatic and hemorrhage as well as systemic dysfunction. According to Schmidt’s criteria, the pancreatic histologic score showed that there existed significant difference in the Cn + LPSgroup in the interstitial edema, inflammatory infiltration, parenchyma necrosis and parenchyma homorrhage incomparison with those of the Cn group, LPS group and NSgroup (P <0.01 or P <0.05). (2) The ultrasturcture of acinarcells was seriously damaged in the Cn + LPS group. Chromatin margination of nucleiwas present, the number and volume of vacuoles greatly increased. Zymmogen granules (ZGs) were genetically decreased in number and endoplasmic reticulumexhibited whorls. swollen mitochondria (3) Pancreatic weight and serum amylase levels in the Cn + LPS was significantly higher than those of the NS group and the LPS group respectively (P <0.01 or P <0.05) .Wever, the pancreatic wet weight and serum amylase concentration showed no significant difference between theCn + LPS group and the Cn group. (4) NO concentration inthe Cn + LPS group was significantly higher than that of NSgroup, LP5 group and Cn group (P <0.05 or P <0.01) .5) TheSOD and MDA concentration of the pancreas in the Cn + LPSgroup were significantly higher than those of NS, LPS and CN groups (P <0.05 or P <0.01). CONCLUSION: The mouse model of severe acute pancreatitis could be induced with caerulein and LPS, which can be non-traumatic and easy to induce, reproducible with the same pathological characteristics as those of SAPin human, and could be used in the research on the mechanism of human SAP.