PATHOPHYSIOLOGIC STUDIES OF EXPERIMENTAL CHRONIC-PANCREATITIS IN RATSINDUCED BY INJECTION OF ZEIN-OLEIC ACID LINOLEIC-ACID SOLUTION INTO THE PANCREATIC DUCT

An experimental model of chronic pancreatitis was induced by a retrogr ade injection of a viscous solution consisting of zein-oleic acid-lino leic acid (0.05 ml/100 g body weight) into the rat pancreatic duct, Hi stologic and biochemical changes were investigated over a period of 6 months after induction of this model. The treated rats gained weight, but pancreatic weight decreased with time. Histologically, the widenin g of acinar lumen and cellular vacuolization occurred within 24 h at t he parenchyma neighboring the small ducts filled with the injected sol ution. Degenerative parenchyma, interstitial edema, and inflammatory c ell infiltration were pronounced 1 week later. Thereafter, duct-like t ubular complex formation progressed, and the exocrine tissue exhibited marked atrophy of the gland with irregular fibrosis and fat replaceme nt over a period of 6 months. Pancreatic contents of protein, amy lase , DNA, and RNA markedly decreased, as did pancreatic weight, whereas h ydroxyproline content increased. Oral administration of camostat did n ot affect pancreatic weight and contents of enzyme in this model. Urin ary para-aminobenzoic acid (PABA) excretion in the BT-PABA test decrea sed to 54% at 6 weeks and 22% at 6 months. Although three quarters of pancreatic immunoreactive insulin (IRI) content was lost after 6 month s, overt diabetes did not occur. The results suggest that an obstructi ve mechanism in the small ducts plays an important role in the genesis and development of chronic pancreatitis.