Effect of short-termed pancreatic duct obstruction on the pancreatic subcellular organellar fragility and pancreatic lysosomal enzyme secretion in rabbits

Abstract

We studied the effect of short-term (3 h) pancreatic duct obstruction (PDO) on the exocrine pancreas and on the secretion of lysosomal enzymes into the pancreatic juice of rabbits during stimulation by pancreatic secretagogues. The following evaluations were made: serum amylase levels, pancreatic water content, pancreatic amylase, trypsinogen and cathepsin B content, and output of pancreatic enzymes and lysosomal hydrolases when stimulated by secretin and caerulein as well as the distribution of cathepsin B in subcellular fraction. Cellular fragility (LDH leakage from dispersed acini) and subcellular organellar fragility (cathepsin B leakage from lysosomes and malate dehydrogenase leakage from mitochondria) were also evaluated. PDO for 3 h plus secretin infusion caused a significant rise in serum amylase levels, pancreatic water content, and pancreatic amylase and trypsinogen content due to congestion of digestive enzymes during PDO. There was also a redistribution of cathepsin B from the lysosomal fraction to the zymogen fraction and increased cellular and subcellular organellar fragility. In normal rabbits and in those with only secretin infusion, caerulein stimulated the secretion of cathepsin B into pancreatic juice. Just after PDO, the secretion of cathepsin B, amylase and trypsinogen significantly decreased. By 24 h after PDO, the output of cathepsin B stimulated by caerulein and secretin had increased significantly. Amylase and trypsinogen output were also significantly increased at this stage, in both the secretin and caerulein fractions. These results indicate that the secretion of lysosomal enzymes into pancreatic juice is stimulated by gut hormones, such as caerulein, in the normal physiological state and in pathological states, such as PDO. These results also show an important role of increased cellular and subcellular organellar fragility in the pathogenesis of pancreatic injuries induced by PDO and augmented secretion of both lysosomal enzymes and pancreatic digestive enzymes in the recovery stage after PDO and their important roles at this stage. Lysosome enzymes also seem to play some physiological roles in the pancreatic ductal system in normal physiological states as well as their roles in pathological states, because cathepsin B can activate trypsinogen, and trypsin can activate many other enzymes.