Review of experimental animal models of biliary acute pancreatitis and recent advances in basic research.
Acute pancreatitis (AP) is a formidable disease, which, in severe forms, causes significant mortality. Biliary AP, or gallstone obstruction-associated AP, accounts for 30-50% of all clinical cases of AP. In biliary AP, pancreatic acinar cell (PAC) death (the initiating event in the disease) is believed to occur as acinar cells make contact with bile salts when bile refluxes into the pancreatic duct. Recent advances have unveiled an important receptor responsible for the major function of bile acids on acinar cells, namely, the cell surface G-protein-coupled bile acid receptor-1 (Gpbar1), located in the apical pole of the PAC. High concentrations of bile acids induce cytosolic Ca(2+)  overload and inhibit mitochondrial adenosine triphosphate (ATP) production, resulting in cell injury to both PACs and pancreatic ductal epithelial cells. Various bile salts are employed to induce experimental AP, most commonly sodium taurocholate. Recent characterization of taurolithocholic acid 3-sulphate on PACs has led researchers to focus on this bile salt because of its potency in causing acinar cell injury at relatively low, sub-detergent concentrations, which strongly implicates action via the receptor Gpbar1. Improved surgical techniques have enabled the infusion of bile salts into the pancreatic duct to induce experimental biliary AP in mice, which allows the use of these transgenic animals as powerful tools. This review summarizes recent findings using transgenic mice in experimental biliary AP.
Pancreatic Diseases Research Group, Department of Integrated Traditional and Western Medicine, West China Hospital, Sichuan University, Chengdu, China.
Mei H
MH
Wan
Wei
W
Huang
Diane
D
Latawiec
Kun
K
Jiang
David M
DM
Booth
Victoria
V
Elliott
Rajarshi
R
Mukherjee
Qing
Q
Xia
D000208:Acute Disease; D000818:Animals; D001647:Bile Acids and Salts / Q000378:metabolism; D002779:Cholestasis / Q000209:etiology* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D042882:Gallstones / Q000139:chemically induced / Q000150:complications* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D005838:Genotype; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D010183:Pancreatic Ducts / Q000378:metabolism* / Q000473:pathology; D010195:Pancreatitis / Q000209:etiology* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D010641:Phenotype; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism
D001647:Bile Acids and Salts; D043562:Receptors, G-Protein-Coupled