ABSTRACT. Obstructive jaundice causes multiple malfunctions in various organs including the pancreas. To establish how such malfunctions occur, we experimentally induced obstructive jaundice through bile duct ligation (BDL) using rats, measured serum bilirubin, amylase and insulin levels, and examined histological, immunohistochemical and cytological changes in the pancreas at 3 days, 1 week, and 4 weeks after the BDL. Morphometrical analysis was also conducted. Serum amylase levels steeply increased at 3 days, and then decreased at 1 and 4 weeks after the BDL to lower than the control level. In contrast, the number of zymogen granules decreased at 3 days after the BDL, then increased and eventually surpassed the control group at 4 weeks after the BDL. On the other hand, serum insulin levels dramatically decreased at 3 days after the BDL but recovered to a level close to that of the control group at 1 week after the BDL. At 4 weeks after the BDL, however, the serum insulin levels again showed a marked decline. Slight decrease in insulin immunoreactivity and number of insulin granules were observed at 4 weeks after the BDL. Cholecystokinin receptors (CCK-R) were expressed in both acinar and islet cells; their immunoreactivity significantly decreased in the acinar cells at 4 weeks after the BDL. Our results suggest that CCK may play a role in regulating changes in the pancreas after obstructive jaundice. It has been reported that pancreatic disorders such as pancreatic cancer and pancreatitis can cause liver damage by physical pressing of the common bile duct to lead to the obstructive jaundice [23]. Although it has been reported that obstructive jaundice can cause pancreatic hyperplasia [2,3], neither the precise morphological changes nor the influence of liver impairment to the pancreas are fully understood. In the present study, we aim to examine changes in secretory activity and histological and cytological features in both the exocrine and endocrine pancreas using rats which were experimentally induced obstructive jaundice.The question is, although there must be multiple factors involved in pancreatic disorders after obstructive jaundice, what could be the most prominent factor? One possible candidate is cholecystokinin (CCK). CCK is a hormone mainly secreted by the duodenum and the proximal jejunum and plays an important role in the secretion of pancreatic enzymes such as amylase. It has also been reported that rats with obstructive jaundice showed elevated serum concentrations of cholecystokinin (CCK) [20,25]. Therefore, we also explored a possible mechanism by immunohistochemistry for CCK receptors. Since CCK-A receptor (CCK-AR) and CCK-B receptor (CCK-BR) is mainly distributed in the gastrointestinal system [24] and the nervous system [30,31], respectively, we focused on CCK-AR in the present study.
MATERIALS AND METHODS
Animals:Nineteen male Wistar rats, 6 weeks of age, weighing between 170 and 190 g, were purchased from Japan Charles River (Kanagawa, Japan) and used as experimental animals. All the rats...