[Effects of analogs of pituitary adenylate cyclase activating polypeptide on acute pancreatitis in rats]

Abstract

Objective: To examine the effects of analogs of pituitary adenylate cyclase activating polypeptide (PACAP)--PACAP6-27 (10, 100 microg/kg) and (4-Cl-D-Phe6, Leu17)VIP (10, 100 microg/kg) on the pancreata of normal rats and on the development of experimental acute pancreatitis.

Methods: Male Wistar rats were allocated into normal control groups, experimental acute pancreatitis groups and PACAP analog intervention groups. Acute pancreatitis was induced with s.c. cerulein and intraductal sodium taurocholate; PACAP analogs were infused intravenously immediately after pancreatitis induction. Pancreatic morphology was observed at 4 h, and serum amylase, pancreatic water content and PACAP contents were measured.

Results: It was found that PACAP6-27 induced pancreatic edema, inflammatory cell infiltration, and elevation of serum amylase [(1464.33 +/- 265.6)-(1692.17 +/- 312.18)] IU/L vs (520.8 +/- 163.27) IU/L of control, P < 0.05); that PACAP6-27 aggravated vacuolization of pancreatic acinar cells in cerulein-induced pancreatitis with hemorrhage and fatty and parenchymal necrosis; and that the pathological changes of cerulein plus 100 microg/kg PACAP group were similar to those of sodium taurocholate-induced pancreatitis. Pancreatic hemorrhage, vacuolization of acinar cells and parenchymal necrosis in sodium taurocholate-induced pancreatitis were worsened by PACAP6-27. (4-Cl-D-Phe6, Leu17)VIP had similar effects. ELISA showed that pancreatic and duodenal levels of PACAP were increased in cerulein- and sodium taurocholate-induced pancreatitis.

Conclusion: PACAP6-27 and (4-Cl-D-Phe6, Leu17)VIP could induce mild pancreatitis and aggravate experimental acute pancreatitis. PACAP probably plays a role in the pathogenesis of acute pancreatitis.