[The cellular and lysosomal fragility of pancreatic acinar cells after ligation of pancreatico-biliary duct in the rat and the protective effects of nafamostat mesilate].
To explore the changes of exorine pancreas in the early stage after ligation of pancreatico-biliary duct (PBD) in rat, we evaluated the changes of serum amylase levels, pancreatic water content as well as the changes of subcellular distribution of cathepsin B in the acinar cells. We also evaluated the lactic dehydrogenase (LDH) discharge from dispersed acini as an index of cellular fragility and cathepsin B leakage from lysosomes as an index lysosomal fragility in vitro study as well as the protective effects of a new synthetic protease inhibitor, nafamostat mesilate (FUT 175) in this model. After ligation of PBD, the serum amylase levels and pancreatic water content, increased significantly compared with those of the control group, but returning to the normal levels at 18 hours. The redistribution of cathepsin B in acinar cells was found and both the cellular and lysosomal fragility increased significantly compared with those of the control groups, shown their peak changes at 12 hours after ligation of PBD. But continuous intravenous administration of FUT 175 (2mg/mg.hr) remarkably attenuated all the parameters. These results indicate the important roles of lysosomal enzyme and lysosomal fragility in the pathogenesis of acute pancreatic injuries in this modes, and the clinical usefulness of FUT 175 in the treatment acute pancreatitis.
Hirano
T
T
First Department of Surgery, Faculty of Medicine, Kyoto University, Japan.
Manabe
T
T
Tobe
T
T
D000208:Acute Disease; D000681:Amylases / Q000378:metabolism; D000818:Animals; D001550:Benzamidines; D001834:Body Water / Q000378:metabolism; D002401:Cathepsin B / Q000378:metabolism; D004195:Disease Models, Animal; D006146:Guanidines / Q000627:therapeutic use*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008247:Lysosomes / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D010179:Pancreas / Q000166:cytology* / Q000201:enzymology / Q000378:metabolism; D010195:Pancreatitis / Q000188:drug therapy*; D051381:Rats; D017208:Rats, Wistar
D001550:Benzamidines; D006146:Guanidines; D007770:L-Lactate Dehydrogenase; D000681:Amylases; D002401:Cathepsin B; C032855:nafamostat