Digestive Diseases and Sciences

, Volume 56, Issue 8, pp 2326–2332

Transient Stasis of Pancreatic Fluid Flow Together with Mild Injury of the Pancreatic Duct Cause Chronic Pancreatitis

  • Taizo Yamaguchi
  • Yasuyuki Kihara
  • Mitsuyoshi Yamamoto
  • Makoto Otsuki
Original Article

DOI: 10.1007/s10620-011-1586-1

Cite this article as:
Yamaguchi, T., Kihara, Y., Yamamoto, M. et al. Dig Dis Sci (2011) 56: 2326. doi:10.1007/s10620-011-1586-1

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.

Aims

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.

Keywords

Synergistic effects Fatty degeneration Type IV collagen MMP-2 

Abbreviations

MMP

Matrix metalloproteinase

ECM

Extracellular matrix

NaTc

Sodium taurocholate

BM

Basement membrane

HE

Hematoxylin and eosin

PBS

Phosphate buffered saline

SDS

Sodium dodecyl sulfate

PAGE

Polyacrylamide gel electrophoresis

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Taizo Yamaguchi
    • 1
  • Yasuyuki Kihara
    • 1
  • Mitsuyoshi Yamamoto
    • 1
  • Makoto Otsuki
    • 1
    • 2
  1. 1.Department of Gastroenterology and Metabolism, School of MedicineUniversity of Occupational and Environmental HealthKitakyushuJapan
  2. 2.Department of Lifestyle-related Diseases and Dietary Life, Graduate School of Life ScienceKobe Women’s UniversitySuma-ku, KobeJapan

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