title: Transient stasis of pancreatic fluid flow together with mild injury of the pancreatic duct cause chronic pancreatitis.
abstract: BACKGROUND
  Little is known about the etiopathogenesis of chronic pancreatitis, due mainly to the lack of simple animal models suitable to study inflammatory and fibrogenetic processes in the pancreas.
  
  
  OBJECTIVE
  The purpose of this study was to examine whether transient congestion of pancreatic fluid flow alone or slight ductal injury alone is sufficient, or where both are required, to induce chronic pancreatic injury.
  
  
  METHODS
  Three different models of pancreatitis were tested in rats induced by retrograde intraductal infusion of 40 μl/100 g body weight of 0.01% agarose (group A), 40 μl/100 g body weight of 0.1% sodium taurocholate (group T), or a mixture of the two solutions (group M). Histological alterations of the pancreas were examined by hematoxylin-eosin staining, changes in type IV collagen structure were studied by immunostaining, and the gelatinolytic activity of latent and active matrix metalloproteinase-2 (MMP-2) was analyzed by zymography.
  
  
  RESULTS
  In group A and T rats, histological alterations of the pancreas and the gelatinolytic activity of MMP-2 returned to baseline levels by day 14, and immunoreactivity for type IV collagen appeared as continuous lines along the basement membrane. In group M rats, however, acinar damage, fibrosis and fatty degeneration were observed even on day 56, and type IV collagen was detected as discontinuous lines until day 56. MMP-2 was significantly elevated from day 5 to day 42.
  
  
  CONCLUSIONS
  Co-existence of transient stasis of pancreatic fluid flow, together with mild damage to the pancreatic duct and acinar cells, exert synergistic effects on the development of persistent pancreatic injury with continuous disorganization of type IV collagen in the basement membrane of the ducts.
authors.affiliation: Department of Gastroenterology and Metabolism, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, 807-8555, Japan.
authors.forename: Taizo
authors.initials: T
authors.lastname: Yamaguchi
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Kihara
authors.forename: Mitsuyoshi
authors.initials: M
authors.lastname: Yamamoto
authors.forename: Makoto
authors.initials: M
authors.lastname: Otsuki
mesh_terms: D000818:Animals; D001485:Basement Membrane / Q000378:metabolism / Q000473:pathology; D024141:Collagen Type IV / Q000378:metabolism; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D010183:Pancreatic Ducts / Q000473:pathology / Q000503:physiopathology*; D010189:Pancreatic Juice / Q000378:metabolism*; D050500:Pancreatitis, Chronic / Q000139:chemically induced / Q000209:etiology* / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D012685:Sepharose / Q000009:adverse effects; D013656:Taurocholic Acid / Q000009:adverse effects
chemical_list: D024141:Collagen Type IV; D013656:Taurocholic Acid; D012685:Sepharose; D020778:Matrix Metalloproteinase 2