Experimental acute biliary pancreatitis induced by retrograde infusion of bile acids into the mouse pancreatic duct

Abstract

Mechanistic studies of acute pancreatitis require animal models because clinical material is generally not available during the early phases of the disease. Here we describe a protocol to induce biliary pancreatitis by retrogradely infusing bile acids into the pancreatic duct of anesthetized mice. The resulting model replicates events believed to be responsible for the onset of clinical biliary (i.e., gallstone) pancreatitis and creates highly reproducible pancreatitis with a severity that depends on the concentration of infused bile acid. Pancreatitis reaches its maximal level of severity within 24 h of induction, and it resolves over the subsequent week. This protocol enables the investigator to use genetically modified strains of mice, and it requires only relatively simple and easily learned techniques of small animal surgery. With practice and gentle technique, the surgery (from induction of anesthesia to completion of the infusion) can be completed within 25 min per animal.

Ryanodine receptors contribute to bile acid-induced pathological calcium signaling and pancreatitis in mice

“…It should be noted that 2-APB is also an inhibitor of SOCE. To evaluate whether our findings with RyR inhibitors on TLCS responses in isolated acinar cells are relevant in vivo, we employed our recently published pancreatitis model in which TLCS is briefly infused in the PD of anesthetized mice (39). This results in inflammation and necrosis of the pancreatic head that is maximal after 24 h (Fig.…”

“…Pancreatitis was induced by retrograde infusion of the bile acid TLCS (3 mM) or taurocholic acid (TC, 37 mM) in the distal common bile duct and pancreatic duct, as recently described (39). Briefly, C57BL/6 mice between 8 and 12 wk (20 -25 g) were anesthetized with a ketamine (120 mg/kg)-xylazine (12 mg/kg) mixture (Butler Schein, Chicago, IL).…”

Bile Acids Induce Pancreatic Acinar Cell Injury and Pancreatitis by Activating Calcineurin

“…Intraductal Bile Acid Infusion Model of Pancreatitis-Pancreatitis was induced by retrograde infusion of the bile acid TLCS (3 mM) or taurocholate (TC) (37 mM) dissolved in saline into the distal common bile duct and pancreatic duct, as recently described (27). Briefly, mice between 8 and 12 weeks (20 -25 g) were anesthetized with a ketamine (120 mg/kg)/xylazine (12 mg/kg) mixture (Butler Schein, Chicago, IL).…”

Physiological and pathophysiological investigation of lacrimal and pancreatic ductal epithelial cells

“…One of the most accepted theories is that bile reflux into the pancreatic ductal system leads to AP. We know from animal studies, that retrograde infusion of bile acids into the pancreatic duct triggers pancreatitis [3,64,65]. Therefore the cytotoxic effects of bile acids have been widely investigated in the pancreas [66][67][68][69] [68,74].…”

“…Numerous studies indicated that bile reflux into the pancreas may lead to pancreatic injury and as a result can induce AP [63][64][65]. Therefore, a better understanding of the mechanisms underlying bile-induced pancreatic injury and its prevention may provide novel therapeutic tools for the treatment of AP.…”