A new model of chronic pancreatitis in rats

Abstract

This study was designed to examine whether continuous pancreatic ductal hypertension (PDH) plays an important role in the onset and development of chronic pancreatitis (CP). Pancreatic, biliary, and duodenal cannulas were implanted in male Wistar rats. PDH was induced by vertically raising the free end of the pancreatic duct cannula to exert a hydrostatic pressure and maintained for 2 wk. PDH was gradually increased, but when the pancreatic juice (PJ) flow was interrupted, PDH was decreased to restore PJ flow. The induction of PDH resulted in a marked reduction of amylase activity in PJ and an increase in serum amylase activity. At 2 wk after persistent PDH, pancreatic exocrine function was markedly decreased in response to a bolus injection of secretin (100 pmol/kg) compared with the control group. Histological examination revealed interlobular as well as intralobular fibrosis in the form of nodular pancreatitis at 2 wk after the induction of PDH. Immunohistochemistry revealed the expression of fibronectin and collagen types I and III. Quantitative real-time RT-PCR showed an increase in transforming growth factor-beta(1) mRNA expression in the pancreas during PDH. The present results suggest that PDH plays an important role in the onset and development of CP. Furthermore, our animal model seems useful for investigating the mechanisms of CP in rats.

Treatment with pravastatin attenuates progression of chronic pancreatitis in rat

“…As there was no significant difference in the average daily food intake among three experimental groups, it is conceivable that treatment with pravastatin prevented body weight loss by improving pancreatic exocrine dysfunction and reducing maldigestion and malabsorption. On the other hand, this experimental model of chronic pancreatitis model shows only little endocrine insufficiency, 11 probably because PDH does not cause inflammation and fibrosis in the islets is due to the different anatomical location from exocrine glands. Therefore, effect of pravastatin on pancreatic endocrine insufficiency was not examined in this study.…”

“…11 In this experimental model, marked inflammatory cells and fibrosis infiltrate into the pancreas, and pancreatic exocrine function markedly deteriorates. As these pathophysiological changes of this rat model closely resemble human chronic pancreatitis, this experimental model seems to be useful for investigating therapeutic strategies for chronic pancreatitis.…”

“…After surgery, the rats were placed into a modified Bollman-type restraint cage. 11 Surgical procedures were conducted according to the method of Green et al 12 During the recovery and experimental periods, the rats had full access to food and water ad libitum.…”

“…The schematic diagram of the experimental model is shown in Figure 2, and details with regard to this experimental model were described previously. 11 PDH was increased by raising the free end of pancreatic cannula 2.5 cm each day until 15 cm. Thereafter, we gradually decreased PDH to preserve pancreatic secretion.…”

“…Serial change of pancreatic ductal pressure during experimental period for induction of chronic pancreatitis ( Figure 3A) was selected according to our previous study. 11 Pravastatin at a dose of 10 mg per kg per day was administrated directly into the duodenum via cannula from 2 days after induction of PDH until the end of experimental period for 12 days (Figure 1). The dose of pravastatin was selected based on the previous studies.…”