Abstract
To investigate the mechanism of fibrosis progression in chronic pancratitis, we studied the process of pancratic fibrosis in dogs after oral administration of ethionine. DL-ethionine at a dose of 130mg/kg/day was perorally given to dogs for 7 days. Mild proliferation of fibroblasts was found in periacinar areas on day 3 after the last feeding of ethionine. On day 7, there was considerable fibrosis with proliferation of fibroblasts. Ethionine at doses of 10, 50 and 100mg/kg was given once or twice a week for 10 or 20 weeks. One week after the last feeding, mild to moderate fibrosis in intra-and interlobular and periductal areas was found. In dogs given ethionine at a dose of 75mg/kg once a week for 15 weeks, formation of fibrous connective tissues was most manifest 2 weeks after the last feeding. An increased staining of typeIII collagen and a less intense staining of type I collagen were found in all zones of fibrosis. Fibronectin was also found between collagen bundles. Such fibrosis decreased thereafter and largely disappeared after 26 weeks, (mild fibrosis was found only in periductal areas). Thus it is likely that the formation of collagen bundles and the resolution of fibrous depositions occur simultaneously between 2 and 4 weeks after the last feeding of ethionine, and that only the resolution of fibrous depositions occurs thereafter. These findings support the view that fibrosis in acute pancreatitis does not generally progress to that in chronic pancreatitis and that fibrosis in chronic pancreatitis probably occurs due to continuous pancreatic injury, which causes the release of pancreatic enzymes.
