Reversible surgical model of biliary inflammation and obstructive jaundice in mice.
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.
Kirkland
Jacob G
JG
Department of Surgery, University of California, San Francisco, VA Medical Center, San Francisco, California 94121, USA.
Godfrey
Cody B
CB
Garrett
Ryan
R
Kakar
Sanjay
S
Yeh
Benjamin M
BM
Corvera
Carlos U
CU
D000469:Alkaline Phosphatase / Q000097:blood; D000818:Animals; D001663:Bilirubin / Q000097:blood; D003135:Common Bile Duct / Q000601:surgery; D005705:Gallbladder Diseases / Q000601:surgery*; D007249:Inflammation / Q000601:surgery*; D041781:Jaundice, Obstructive / Q000601:surgery*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009195:Peroxidase / Q000378:metabolism; D011183:Postoperative Complications / Q000473:pathology / Q000517:prevention & control; D013525:Surgical Instruments
D009195:Peroxidase; D000469:Alkaline Phosphatase; D001663:Bilirubin