Abstracts
1998 Digestive Disease Week
#1013
SEVERE HYPERSTIMULATION/OBSTRUCTION PANCREATITIS: A MODEL CHARACTERIZED BY ACINAR ATROPHY AND INTERSTITIAL PANCREATIC FIBROSIS. K. Murayama*, B. Barent+, A. Brooks+, M. Gruber+, S. Eliason@, E. Brunt@, G. Smith*. Depts of *Surgery and @Pathology, St. Louis University, St. Louis, MO and +Dept of Surgery, University of Nebraska Medical Center, Omaha, NE.
Significant fibrosis and acinar atrophy are characteristics of chronic pancreatitis, however, due to the lack of a reproducible model the acute phase of these changes is poorly understood. We have developed a model of severe hyperstimulation/
obstruction pancreatitis (SHOP) to better define the mechanisms of the early phase of pancreatic fibrogenesis.
METHODS: Sprague-Dawley rats were used and SHOP was induced in 15 rats by complete pancreatic duct obstruction and daily cerulein hyperstimulation (25 µg/kg, ip). Rats were sacrificed at 24h (n=4), 48h (n=4), 72h (n=3), and 96h (n=4). Controls underwent sham operation and received no cerulein. Pancreata were divided and prepared for H&E and sirius red staining (collagen specific), immunofluorescence microscopy (anti-human collagen antibody), and hydroxyproline assay (measure of total collagen content). A modified H&E grading system was used quantifying edema (0-3), inflammation (0-3), acinar necrosis (0-6), acinar atrophy (0-6), and hemorrhage (0-5). Sirius red was scored as follows:
Sirius red (1=normal, 2=moderate amts of interstitial collagen, 3=prominent collagen in periacinar and perivascular areas)
RESULTS:
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H&E
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sirius
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hydroxy-
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Edema
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inflam
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necros
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acin atr
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hemo
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red
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proline
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Control
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1 ± 0
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0 ± 0
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0 ± 0
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0 ± 0
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0 ± 0
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1 ± 0
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14.4 ± 1.3
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24h
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1.5 ± .3
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1.3 ± .3*
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.5 ± .5
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0 ± 0
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.3 ± .3
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1 ± 0
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13.5 ± 1.0
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48h
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2.8 ± .3*
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2.8 ± .3*
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2.8 ± .5*
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2.3 ± .3*
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1.8 ± 1.1
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2 ± 0*
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15.9 ± 2.5
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72h
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2.3 ± .3*
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2.3 ± .3*
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2 ± 0*
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4.7 ± .7*
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.3 ± .3
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2.3 ± .3*
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23.3 ± 1.4*
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96h
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2.8 ± .3*
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2.5 ± .3*
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2 ± 0*
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6.0 ± 0*
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.8 ± .8
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3 ± 0*
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34.6 ± 1.8
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-results are expressed as mean ± SEM; *p < 0.05 compared to controls
Immunofluorescence microscopy demonstrated a progressive increase in collagen deposition in the periacinar spaces and loss of normal acinar architecture. Over 96 hr, SHOP was characterized by (1) acinar atrophy with appearance of duct-like complexes, (2) increased total pancreatic collagen, and (3) increased periacinar collagen deposition.
CONCLUSIONS: SHOP is a novel model of pancreatitis associated with edema and inflammation, but minimal necrosis and hemorrhage. Furthermore, SHOP is characterized by significant collagen deposition and acinar atrophy with replacement by duct-like complexes making it an ideal model to study the early cellular mechanisms of pancreatic fibrogenesis.
Copyright 1996 - 1998, SSAT, Inc. Revised 29 June 1998.
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