Pancreaticobiliary maljunction-associated pancreatitis: an experimental study on the activation of pancreatic phospholipase A2.
Congenital dilatation of the bile duct (CDBD), or choledochalcyst, is often complicated by recurrent pancreatitis. Reflux of pancreatic juice into the bile duct through pancreaticobiliary maljunction (PBM), an anomaly commonly associated with CDBD, and ensuing activation of pancreatic enzymes could be involved in the pathophysiologic mechanism of recurrent pancreatitis. A study was undertaken to follow the time course of the activity of phospholipase A2 (PLA2) in animal models of PBM. The assay procedures for PLA2 were evaluated, as were the conditions for separating the active enzyme from its inactive proenzyme (pro-PLA2) by immunoblotting. A rat model was designed according to Block's method with some modifications. The kinetics of prophospholipase A2 (proPLA2) activation in bile was examined by measuring PLA2 activity and by immunoblotting using anti-rat pancreatic enzyme antibody after separating PLA2 from its zymogen under nonreducing conditions. Experimental animals were divided into three groups: group 1 (PBM group) in which bile and pancreatic juice were mixed with occlusion of the papilla; group 2, in which the papilla and hepatic hillus were occluded without mixing the two juices; and group 3, in which simple laparotomy was done. In group 1 animals, pro-PLA2 in bile was activated to its active form. In group 2 animals, where proPLA2 was predominant, there was only slight elevation of PLA2 activity in bile. In group 1 an immunohistologic study demonstrated localization of PLA2 around necrotic foci in the pancreatic parenchyma. These results suggest the involvement of activated PLA2 in the pathogenesis of choledochal cystassociated pancreatitis.
Nakamura
T
T
Department of Pediatric Surgery, Osaka University Medical School, Japan.
Okada
A
A
Higaki
J
J
Tojo
H
H
Okamoto
M
M
D000818:Animals; D001652:Bile Ducts / Q000002:abnormalities*; D015529:Choledochal Cyst / Q000150:complications*; D004789:Enzyme Activation; D015151:Immunoblotting; D010179:Pancreas / Q000201:enzymology*; D010195:Pancreatitis / Q000209:etiology*; D010741:Phospholipases A / Q000378:metabolism*; D054467:Phospholipases A2; D051381:Rats; D017208:Rats, Wistar; D012008:Recurrence
D010741:Phospholipases A; D054467:Phospholipases A2