Effects of early decompression and cholecystokinin inhibition in rats with acute pancreatitis induced by bile-pancreatic-duct obstruction.
Biologic data related to pancreatic regeneration and acinar-cell homeostasis after ductal decompression would be useful in clinical settings to elucidate the time at which obstructions in human biliary acute pancreatitis (AP) should be removed. Our aim was to evaluate the outcome of AP after early removal of bile-pancreatic-duct obstruction (BPDO) and to ascertain whether cholecystokinin (CCK) blockade accelerates recovery from the disease. We conducted analysis of apoptosis and cell cycle, as well as measurements of enzyme and calcium load, in acinar cells using flow cytometry to ascertain the capability of the pancreas to regain its function after AP. Male Wistar rats were subjected to AP by means of BPDO for 6 hours and 24 hours. In other groups, the BPDO was opened 24 hours after induction; 3 days and 7 days later they were killed. Half of the rats in which the BPDO was opened were administered L364,718, a CCK-receptor antagonist (0.1 mg/kg/12 hours), 30 minutes before the induction of BPDO. Plasma amylase activity, hematocrit, and pancreatic weight returned to control values after BPDO opening. The highest degree of oxidative stress was found in the pancreases of rats subjected to BPDO for 6 hours, as indicated by the decrease in pancreatic glutathione content, but it was not restored 7 days after BPDO opening. Cell-cycle distribution, as measured with propidium iodide DNA staining, showed increases in the proportion of acinar cells in S-phase from 3 days after BPDO opening in L364,718-treated and nontreated rats. Annexin V-fluorescein isothiocyanate labeling revealed deletion of acinar cells by way of apoptosis 3 days after BPDO opening. However, it may be compensated 7 days after BPDO opening because regardless of whether rats were treated with L364,718, significant increases in synthesis and mitosis were detected. Accumulation of digestive enzymes and calcium in acinar cells was found during BPDO, but this appeared to have normalized 3 days after BPDO opening and onward in both L364,718-treated and nontreated rats. In conclusion, early removal of obstruction allowed rapid cell proliferation and prevented the progression of severe alterations within acinar cells induced by BPDO. CCK blockade does not accelerate pancreatic recovery after BPDO opening.
de Dios
Isabel
I
Department of Physiology and Pharmacology, University of Salamanca, Campus Miguel de Unamuno, 37007 Salamanca, Spain. bel@gugu.usal.es
Urunuela
Aranzazu
A
Manso
Manuel
M
D000208:Acute Disease; D000681:Amylases / Q000032:analysis; D000818:Animals; D017209:Apoptosis; D002118:Calcium / Q000378:metabolism; D002453:Cell Cycle; D002766:Cholecystokinin / Q000037:antagonists & inhibitors*; D001651:Cholestasis, Extrahepatic / Q000378:metabolism / Q000503:physiopathology*; D019299:Decompression, Surgical; D020109:Devazepide / Q000627:therapeutic use; D004195:Disease Models, Animal; D005434:Flow Cytometry; D006727:Hormone Antagonists / Q000627:therapeutic use; D008297:Male; D010179:Pancreas / Q000378:metabolism / Q000473:pathology; D010183:Pancreatic Ducts / Q000378:metabolism / Q000503:physiopathology*; D010195:Pancreatitis / Q000378:metabolism / Q000503:physiopathology*; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D014362:Trypsinogen / Q000032:analysis
D006727:Hormone Antagonists; D014362:Trypsinogen; D002766:Cholecystokinin; D000681:Amylases; D020109:Devazepide; D002118:Calcium