Differences Of Pancreatic Injury And Regeneration In Acute Pancreatitis Of C57BL/6 And FVB/N Mouse Strain

ObjectivesOur objective of this study was to establish an experimental mouse AP model with cerulein treatment and to explore the susceptibility of mouse strains on the severity of pancreatic injury and the subsequent repair and regeneration.MethodsC57BL/6 and FVB/N mouse strains were used in this study,24 mice for each strain.Mice were randomly divided into four groups for each strain:the control group(CON),AP 1d,AP 3d and AP 7d group,6 mice for each group.AP was induced in WT C57BL/6 and FVB/N mice,via six hourly i.p.injections of cerulein dissolved in 0.9%saline(100?g/kg)administered on four consecutive days.Mice were sacrificed on indicated time points after last cerulein treatment,e.g.1,3 and 7 days,pancreas tissues were harvested for further analysis.H&E staining was performed to observe pancreas histopathology and subsequent repair and regeneration process.Immunofluorescence staining on pancreas tissue revealed the expression of a-AMY,MPO and Cleaved Caspase-3.Immunohistochemistry study of pancreas was used to examine IL-1?,NF-?B,Ki67 expression.Cell apoptosis in pancreas was detected via TUNEL examination.ResultsCompared to CON group,AP mice showed significant more severe pancreatic injury,increased pancreatic injury score and decreased pancreatic AMY+ area,thus indicated that this cerulein-induced AP model was established successfully.Compared to C57BL/6 mice,FVB/N mice showed more severe pancreatic injury and significant higher pancreatic injury score of AP 1d,3d and 7d groups.Analyses of MPO,IL-1?and NF-?B showed that FVB/N strain exhibited more severe inflammation in the pancreas compared to C57BL/6 mice.FVB/N mice exhibited more Caspase-3+ cell and TUNEL+ cell in injured pancreas compared to C57BL/6 mice,which indicated that the pancreas of FVB/N mice exhibited more apoptosis compared to C57BL/6 mice.Analysis of Ki67 revealed increased Ki67+ cells in injured pancreatic areas of FVB/N mice compared to C57BL/6 mice,which indicated a more active cellular proliferation in FVB/N mice.ConclusionThese results demonstrated that there exists differential susceptibility on pancreatic injury and regeneration between FVB/N and C57BL/6 mice in the cerulein-induced AP.Compared to C57BL/6 strain,FVB/N mice were more susceptible to the ceulein-induced injury,characterized by more severe pancreas damage and poorer recovery.