Reversible Surgical Model of Biliary Inflammation and Obstructive Jaundice in Mice

Department of Surgery, University of California, San Francisco, VA Medical Center, San Francisco, California 94121, USA.
Journal of Surgical Research (Impact Factor: 1.94). 09/2009; 164(2):221-7. DOI: 10.1016/j.jss.2009.08.010
Source: PubMed


Common bile duct (CBD) ligation is used in animal models to induce biliary inflammation, fibrosis, and cholestatic liver injury, but results in a high early postoperative mortality rate, probably from traumatic pancreatitis. We modified the CBD ligation model in mice by placing a small metal clip across the lower end of the CBD. To reverse biliary obstruction, a suture was incorporated within the clip during its placement. The suture and clip were removed on postoperative d 5 or 10 for biliary decompression. After 5 d of biliary obstruction, the gallbladder showed an 8-fold increase in wall thickness and a 17-fold increase in tissue myeloperoxidase activity. Markedly elevated serum levels of alkaline phosphatase and bilirubin indicated injury to the biliary epithelium and hepatocytes. Early postoperative (d 0-2) survival was 100% and later (d 3-5) survival was 85% (n=54 mice). We successfully reversed biliary obstruction in 20 mice (37%). Overall survival after reversal was 70%. In surviving mice, biliary decompression was complete, inflammation was reduced, and jaundice resolved. Histologic features confirmed reduced epithelial damage, edema, and neutrophil infiltration. Our technique minimized postoperative death, maintained an effective inflammatory response, and was easily reversible without requiring repeat laparotomy. This reversible model can be used to further define molecular mechanisms of biliary inflammation, fibrosis, and liver injury in genetically altered mice.

13 Reads
  • [Show abstract] [Hide abstract]
    ABSTRACT: AIM: To develop rat models of acute and chronic obstructive jaundice and to evaluate the extent to which they mimic features of clinical diseases. METHODS: Ninety Sprague-Dawley rats were randomly and equally divided into three groups: acute obstructive jaundice group, chronic obstructive jaundice group, and control group. Each group was further divided into five subgroups for testing at different time points. Liver function was determined and the diameter of the common bile duct was measured under a microscope at weeks 1, 2, 3, 4, and 5 after model induction. Pathological changes in liver tissue were also observed by microscope. Choledochoduodenostomy was performed at week 4. RESULTS: Jaundice progressively worsened in rats with acute obstructive jaundice, and TBIL increased from 84.86 μmol/L ± 49.09 μmol/L at week 1 to 749.38 μmol/L ± 38.99 μmol/L at week 4. Meanwhile, the diameter of the common bile duct diameter increased from 0.35 cm ± 0.15 cm to 1.50 cm ± 0.30 cm, and obvious degeneration, necrosis and hyperplasia of liver cells were observed. Jaundice was obviously improved after choledochoduodenostomy (TBIL: 153.93 μmol/L ± 57.36 μmol/L; diameter of the common bile duct: 0.40 cm ± 0.20 cm). Jaundice was mild in rats with chronic obstructive jaundice, and TBIL decreased from 42.43 μmol/L ± 23.56 μmol/L at week 1 to 36.52 μmol/L ± 16.28 μmol/L at week 4. Meanwhile, the diameter of the common bile duct increased from 0.20 cm ± 0.15 cm to 0.30 cm ± 0.10 cm, and obvious degeneration and hyperplasia of liver cells were noted. Jaundice slowly subsided after choledochoduodenostomy (TBIL: 32.15 μmol/L ± 13.20 μmol/L; diameter of the common bile duct: 0.15 cm ± 0.10 cm). Total bilirubin and the diameter of the common bile duct differed significantly at different time points between rats with acute and chronic obstructive jaundice (both P < 0.05). CONCLUSION: Rat models of acute and chronic obstructive jaundice have been successfully established. There were significantly different manifestations between rats with chronic and acute obstructive jaundice.
    No preview · Article · Jan 2011 · World Chinese Journal of Digestology
  • [Show abstract] [Hide abstract]
    ABSTRACT: Biodegradable isocyanate-functional adhesives based on poly(ethylene glycol)-adipic acid esters were synthesized, characterized, and evaluated in vitro and in vivo. Two types of formulations, P2TT and P2MT, were developed by functionalization with 2,4-tolylene diisocyanate (TDI) or 4,4'-methylene-bis(phenyl isocyanate) (MDI), respectively, and branching with 1,1,1-trimethylolpropane (TMP). The biocompatibility of the synthesized adhesive formulations was evaluated as per ISO 10993. Cytotoxicity, systemic toxicity, pyrogenicity, genotoxicity (reverse mutation of Salmonella typhimurium and Escherichia coli), hemolysis, intracutaneous reactivity, and delayed-type hypersensitivity were evaluated. All formulations met the requirements of the conducted standard tests. The biological behavior and ability of the adhesive formulations to close an arteriotomy and withstand arterial pressure following partial approximation with a single suture were evaluated in a rat abdominal aorta model. Animals were evaluated at 1, 2, 3, and 4 weeks after surgery. Macroscopic and histopathologic evaluation of explanted arteries suggested that the P2TT formulation had better in vivo performance than the P2MT formulation. Additionally, the P2TT formulation resulted in less tissue reaction than P2MT formulation. To our knowledge, this is the first study demonstrating the potential of this new class of isocyanate-functional degradable adhesives for vascular applications.
    No preview · Article · Oct 2011 · Journal of Biomedical Materials Research Part B Applied Biomaterials

  • No preview · Article · Jan 2012
Show more