Pancreaticobiliary Maljunction‐Associated Pancreatitis: An Experimental Study on the Activation of Pancreatic Phospholipase A2

Abstract Congenital dilatation of the bile duct (CDBD), or choledochal cyst, 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 A 2 (PLA 2 ) in animal models of PBM. The assay procedures for PLA 2 were evaluated, as were the conditions for separating the active enzyme from its inactive proenzyme (pro‐PLA 2 ) by immunoblotting. A rat model was designed according to Block's method with some modifications. The kinetics of prophospholipase A 2 (proPLA 2 ) activation in bile was examined by measuring PLA 2 activity and by immunoblotting using anti‐rat pancreatic enzyme antibody after separating PLA 2 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 hilus were occluded without mixing the two juices; and group 3, in which simple laparotomy was done. In group 1 animals, pro‐PLA 2 in bile was activated to its active form. In group 2 animals, where proPLA 2 was predominant, there was only slight elevation of PLA 2 activity in bile. In group 1 an immunohistologic study demonstrated localization of PLA 2 around necrotic foci in the pancreatic parenchyma. These results suggest the involvement of activated PLA 2 in the pathogenesis of choledochal cyst‐associated pancreatitis.