A new experimental model for gallstone pancreatitis: short-termed pancreatico-biliary duct obstruction and exocrine stimulation with systemic hypotension in rats.
The effects of short-termed (2 hours) obstruction of pancreatico-biliary duct (PBDO) and exocrine stimulation (IDH) by caerulein infusion (0.2 microgram/kg.hr) with systemic hypotension (SH) (30% reduction of mean arterial pressure for 30 min) on the exocrine pancreas were evaluated in the rat. PBDO and IDH with SH caused more significant rises in portal serum amylase, cathepsin B and malate dehydrogenase levels, and pancreatic water content as well as more significant redistribution of cathepsin B activity from the lysosomal fraction to the zymogen fraction in the subcellular fractionations than only PBDO, or PBDO with IDH, or PBDO with SH group. In addition, more accelerated lysosomal and mitochondrial fragility were observed in the PBDO and IDH with SH group. Moreover, PBDO and IDH with SH caused an activation of larger amount of trypsinogen in the pancreas compared with other groups (PBDO with IDH and PBDO with SH group). These results indicate that present model of short-termed PBDO and exocrine stimulation with systemic hypotension seems to be pertinent model for gallstone pancreatitis in humans, and that redistribution of lysosomal enzymes and subcellular organellar fragility seem to play an important role in the pathogenesis of pancreatic injuries by PBDO, particularly with exocrine stimulation and pancreatic ischaemia, probably via activation of trypsinogen to trypsin by lysosomal enzyme such as cathepsin B.
Hirano
T
T
First Department of Surgery, Faculty of Medicine, Kyoto University, Japan.
Manabe
T
T
D000818:Animals; D001652:Bile Ducts / Q000502:physiology; D002108:Ceruletide / Q000494:pharmacology; D002769:Cholelithiasis / Q000150:complications*; D004195:Disease Models, Animal; D007022:Hypotension / Q000503:physiopathology; D008297:Male; D010179:Pancreas / Q000187:drug effects / Q000503:physiopathology; D010183:Pancreatic Ducts / Q000502:physiology; D010195:Pancreatitis / Q000209:etiology*; D051381:Rats; D017208:Rats, Wistar
D002108:Ceruletide