title: Intraductal infusion of taurocholate followed by distal common bile duct ligation leads to a severe necrotic model of pancreatitis in mice.
abstract: OBJECTIVE
  The most common etiology of acute pancreatitis results from the impaction of gallstones or sludge in the distal common bile duct (CBD). The result is pancreatic duct obstruction, diversion of bile into the pancreas, or cholestasis. In the current study, we examined whether combining both aspects, that is, infusion of the bile acid taurocholate (TC) followed by bile duct ligation (BDL), could yield a more severe form of pancreatitis that mimics biliary pancreatitis.
  
  
  METHODS
  In mice, after laparotomy, the CBD was infused with either normal saline (NS) or TC. Subsequently, the CBD was ligated at the ampulla.
  
  
  RESULTS
  Mice receiving TC infusion followed by BDL (TC + BDL) had higher mortality compared with animals receiving intraductal NS with BDL (NS + BDL). The TC + BDL arm developed more severe and diffuse pancreatic necrosis. In addition, serum amylase, IL-6, and bilirubin were significantly higher. However, pancreatic edema as well as lung and liver injury were unchanged between TC + BDL and NS + BDL.
  
  
  CONCLUSIONS
  In summary, the combination of bile infusion into the pancreas followed by BDL causes a more severe, necrotizing pancreatitis. We believe that this novel model of pancreatitis is useful because it can be used in transgenic mice and recapitulates several aspects of biliary pancreatitis.
authors.affiliation: Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, PA; †Department of General Surgery, Xiangya Hospital, Central South University, Changsha, Hunan, China; and ‡Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA.
authors.forename: Tianming
authors.initials: T
authors.lastname: Le
authors.forename: John F
authors.initials: JF
authors.lastname: Eisses
authors.forename: Kathryn L
authors.initials: KL
authors.lastname: Lemon
authors.forename: John A
authors.initials: JA
authors.lastname: Ozolek
authors.forename: Derek A
authors.initials: DA
authors.lastname: Pociask
authors.forename: Abrahim I
authors.initials: AI
authors.lastname: Orabi
authors.forename: Sohail Z
authors.initials: SZ
authors.lastname: Husain
mesh_terms: D000681:Amylases / Q000097:blood; D000818:Animals; D001663:Bilirubin / Q000097:blood; D015415:Biomarkers / Q000097:blood; D002779:Cholestasis / Q000150:complications*; D003135:Common Bile Duct / Q000601:surgery*; D004195:Disease Models, Animal; D042882:Gallstones / Q000139:chemically induced*; D015850:Interleukin-6 / Q000097:blood; D008026:Ligation; D008297:Male; D051379:Mice; D010179:Pancreas / Q000201:enzymology / Q000473:pathology; D019283:Pancreatitis, Acute Necrotizing / Q000097:blood / Q000139:chemically induced* / Q000473:pathology; D012720:Severity of Illness Index; D013656:Taurocholic Acid; D013997:Time Factors
chemical_list: D015415:Biomarkers; D015850:Interleukin-6; C577686:interleukin-6, mouse; D013656:Taurocholic Acid; D000681:Amylases; D001663:Bilirubin