[Changes of acinar cells in the pancreato-biliary duct ligation with exocrine pancreatic stimulation model in rats; protective effects of a new potent protease inhibitor, ONO3307].
To evaluate the changes of pancreatic acinar cells in the pancreatic duct obstructed animals as well as the protective effects of a new potent protease inhibitor, ONO3307, we measured the serum amylase levels, pancreatic water content, histological changes, lysosomal fragility in in-vitro incubation, cathepsin B distribution in acinar cells, and cathepsin B and amylase output into pancreatic juice after short-termed (3 hrs) pancreatic duct obstruction with caerulein (0.2 micrograms/kg.hr) infusion in rats. Serum amylase levels, pancreatic water content, and lysosomal fragility in duct obstructed with caerulein infused animals were significantly increased compared with the control groups, and remarkable shift of cathepsin B from lysosomal fraction to zymogen fraction was observed in this group. These changes tended to continue 24 hours after removal of duct obstruction. But with infusion of ONO3307, these changes observed in duct-obstructed with caerulein infusion groups were significantly, almost completely attenuated. These results indicate the intimate relationship between the pathogenesis of acute pancreatitis and lysosomes and some known proteases which are inhibited by ONO 3307 and suggest the usefulness of such a kind of protease inhibitor in the treatment of acute pancreatitis.
Hirano
T
T
First Department of Surgery, Faculty of Medicine, Kyoto University, Japan.
Yotsumoto
T M
TM
Ando
K
K
Tobe
T
T
D000208:Acute Disease; D000681:Amylases / Q000378:metabolism; D000818:Animals; D001652:Bile Ducts; D002401:Cathepsin B / Q000378:metabolism; D004195:Disease Models, Animal; D006146:Guanidines / Q000494:pharmacology*; D008026:Ligation; D008297:Male; D010179:Pancreas / Q000187:drug effects* / Q000201:enzymology; D010183:Pancreatic Ducts / Q000502:physiology; D010195:Pancreatitis / Q000473:pathology / Q000517:prevention & control; D011312:Pressure; D051381:Rats; D011919:Rats, Inbred Strains; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology*
D006146:Guanidines; D015842:Serine Proteinase Inhibitors; C062836:ONO 3307; D000681:Amylases; D002401:Cathepsin B