Human urinary trypsin inhibitor, urinastatin, prevents pancreatic injuries induced by pancreaticobiliary duct obstruction with cerulein stimulation and systemic hypotension in the rat
T. Hirano and T. Manabe
First Department of Surgery, Faculty of Medicine, Kyoto University, Japan.
OBJECTIVE: The protective effects of human urinary trypsin inhibitor
against pancreatic injuries in multifactor-related experimental model of
acute pancreatitis were evaluated. DESIGN: Experimental study. MATERIALS
AND METHODS: Acute pancreatitis was induced by short-termed (1-hour)
pancreatico-biliary duct obstruction with cerulein stimulation (30 minutes;
0.2 microgram/kg per hour) and systemic hypotension (30 minutes; 30%
reduction of mean arterial pressure) in rats. In this model, the protective
effects of UTI against pancreatic injuries were evaluated at a dose of
10,000 U/kg per hour. RESULTS: In this model, significant increases in
portal serum amylase, cathepsin B and malate dehydrogenase levels were
observed as compared with the control rats. The redistribution of cathepsin
B from the lysosomal to the zymogen fraction and activation of trypsinogen
were also observed. Moreover, the increased lysosomal and mitochondrial
fragility as well as impaired pancreatic adenylate energy metabolism were
noted. The therapeutic administration of human urinary trypsin inhibitor
had significant protective effects against these pancreatic injuries.
Furthermore, the combined prophylactic and therapeutic administration of
human urinary trypsin inhibitor had more significant protective effects
than only therapeutic treatment. CONCLUSIONS: These results suggest the
importance of timing and of selecting a pertinent protease inhibitor, such
as urinary trypsin inhibitor, in the treatment of pancreatitis.
