Characterization of a novel model of pancreatic fibrosis and acinar atrophy.
Significant fibrosis and acinar atrophy are characteristics of chronic pancreatitis; however, because of the lack of a reproducible model, early phases of these changes are poorly understood. We have developed a model of severe hyperstimulation and obstruction pancreatitis (SHOP) to better define the mechanisms of early pancreatic fibrogenesis. Sprague-Dawley rats were used and SHOP was induced by complete pancreatic duct obstruction and daily cerulein hyperstimulation (50 microg/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 (measure of total collagen content). We found moderate amounts of edema and inflammation 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 necrosis and a significant decrease in acinar cell mass, making it an ideal model to study the early cellular mechanisms of pancreatic fibrogenesis.
Murayama
K M
KM
Department of Surgery, Saint Louis University Health Sciences Center, Theodore Cooper Surgical Research Institute, St. Louis, Missouri 63110-0250, USA.
Barent
B L
BL
Gruber
M
M
Brooks
A
A
Eliason
S
S
Brunt
E M
EM
Smith
G S
GS
D000681:Amylases / Q000097:blood; D000818:Animals; D001284:Atrophy; D001391:Azo Compounds; D002108:Ceruletide / Q000008:administration & dosage / Q000009:adverse effects; D002908:Chronic Disease; D003094:Collagen / Q000032:analysis; D004396:Coloring Agents; D004195:Disease Models, Animal; D004487:Edema / Q000473:pathology; D004801:Eosine Yellowish-(YS); D005355:Fibrosis; D005456:Fluorescent Dyes; D006416:Hematoxylin; D006909:Hydroxyproline / Q000032:analysis; D007274:Injections, Intraperitoneal; D008297:Male; D009336:Necrosis; D010179:Pancreas / Q000473:pathology*; D010183:Pancreatic Ducts / Q000601:surgery; D010195:Pancreatitis / Q000097:blood / Q000209:etiology / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D001391:Azo Compounds; D004396:Coloring Agents; D005456:Fluorescent Dyes; C062246:Direct Red 81; D002108:Ceruletide; D003094:Collagen; D000681:Amylases; D006909:Hydroxyproline; D004801:Eosine Yellowish-(YS); D006416:Hematoxylin