Experimental Study on the Influence of Pancreatic Duct Obstruction on Pancreatic Lysosome in Rabbits and its Protection by a Protease Inhibitor

Tetsuya Hirano, Tadao Manabe, Takayoshi Tobe

First Department of Surgery, Faculty of Medicine, Kyoto University

To evaluate the changes in pancreatic acinar cells in pancreatic duct obstruction as well as the protective effects of a new potent protease inhibitor, E3123, we measured the portal serum amylase and cathepsin B levels, pancreatic water content, pancreatic amylase and cathepsin B content, histological changes, as well as the cathepsin B distribution in acinar cells and lysosomal fragility in in-vitro incubation after short-term (3 hours) pancreatic duct obstruction by secretin (0.2 U/kg·hr) infusion in rabbits. Portal serum amylase, cathepsin B levels, pancreatic water content, pancreatic amylase content and lysosomal fragility in duct-obstructed animals were significantly increased compared with the control group, and a marked shift of cathepsin B activity from the lysosomal fraction to the zymogen fraction was observed in this group. These changes had almost disappeared 24 hours after the removal of duct obstruction with only a slight remnant of the cathepsin B redistribution. However when E3123 was infused at a dose of 5 mg/kg·hr during the duct obstruction, these changes observed in the duct-obstructed group were almost completely inhibited. A dose of 2 mg/kg·hr also have a protective effect against hyperamylasemia and cathepsin B redistribution. These results indicate the important role of lysosomal enzymes and the therapeutic effect of E3123 on the subcellular levels in the pathogenesis of acute pancreatitis.

Key words
pancreatic duct obstruction, protease inhibitor E-3123, lysosomal fraqility, redistribution of lysosomal enzyme, cathepsin B

Reprint requests
Tetsuya Hirano First Department of Surgery, Faculty of Medicine, Kyoto University
54 Shogoin-Kawaracho, Sakyoku, Kyoto, 606 JAPAN

Accepted
April 1, 1992

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