A mouse model of acute biliary pancreatitis induced by retrograde pancreatic duct infusion of Na-taurocholate.
OBJECTIVE
Most mechanistic studies of pancreatitis in mice employ the secretagogue-induced model. The currently reported studies were designed to develop an alternative, and possibly more clinically relevant, mouse model of pancreatitis.


METHODS
Na-taurocholate (10-50 microl, 1-5%) in saline, or saline alone, was retrogradely infused into the mouse pancreatic duct. The animals were killed 6-24 hours later and the severity of pancreatitis in the pancreatic head and tail was examined by quantitating hyperamylasemia, pancreatic edema, acinar cell necrosis, and pancreatic inflammation. In addition, intrapancreatic activation of trypsinogen, generation of IL-6, intrapulmonary sequestration of neutrophils, and alterations in lung compliance were evaluated. The effects of Na-taurocholate on in-vitro acinar cell calcium transients, viability, and trypsinogen activation were examined.


RESULTS
Little or no evidence of pancreatitis was observed in mice infused with saline alone or in the tail of pancreata removed from animals infused with Na-taurocholate. In the head of the pancreas, evidence of pancreatitis was observed 12-24 hours after infusion of 20-50 microl 2-5% Na-taurocholate and the earliest morphological changes involved terminal duct and acinar cells. Intrapancreatic trypsin activity was transiently elevated within 5 minutes of Na-taurocholate infusion and pancreatic IL-6 levels were elevated 24 hours later. Under in-vitro conditions, Na-taurocholate triggered pathological acinar cell calcium transients, cell death, and calcium-dependent trypsinogen activation.


CONCLUSIONS
This clinically relevant model of acute biliary pancreatitis yields reproducible results and its severity can be easily manipulated. It is ideally suited for use in mechanistic studies employing genetically modified mouse strains.
Laukkarinen
Johanna M
JM
Department of Gastroenterology and Alimentary Tract Surgery, Tampere University Hospital, Tampere, Finland.
Van Acker
Gijs J D
GJ
Weiss
Eric R
ER
Steer
Michael L
ML
Perides
George
G
D000208:Acute Disease; D000818:Animals; D001660:Biliary Tract Diseases / Q000139:chemically induced*; D002756:Cholagogues and Choleretics; D004195:Disease Models, Animal; D005260:Female; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010183:Pancreatic Ducts; D010195:Pancreatitis / Q000139:chemically induced*; D011014:Pneumonia / Q000139:chemically induced; D015203:Reproducibility of Results; D013656:Taurocholic Acid
D002756:Cholagogues and Choleretics; D015850:Interleukin-6; D013656:Taurocholic Acid