Characterization of a novel model of pancreatic fibrosis and acinar atrophy

Significant fibrosis and acinar atrophy are characteristics of chronic panc reatitis; however, because of the lack of a reproducible model, early phase s of these changes are poorly understood. We have developed a model of seve re hyperstimulation and obstruction pancreatitis (SHOP) to better define th e mechanisms of early pancreatic fibrogenesis. Sprague-Dawley rats were use d and SHOP was induced by complete pancreatic duct obstruction and daily ce rulein hyperstimulation (50 mu g/kg intraperitoneally). Animals were killed at 24, 48, 72, and 96 hours. Control animals underwent sham operation and received no cerulein. Pancreata were prepared for hematoxylin and eosin and sirius red (collagen-specific) staining and for hydroxyproline assay (meas ure of total collagen content). We found moderate amounts of edema and infl ammation but minimal parenchymal necrosis. Significant loss of acinar cell mass was noted by 48 hours, and normal acinar cells were essentially absent by 96 hours. Tissue collagen content increased with time and large amounts of interstitial collagen were detected by 72 hours. In conclusion, SHOP is a novel model of early pancreatic fibrosis associated with minimal necrosi s and a significant decrease in acinar cell mass, making it an ideal model to study the early cellular mechanisms of pancreatic fibrogenesis.