A novel murine model of reversible bile duct obstruction demonstrates rapid improvement of cholestatic liver injury

We have established a novel surgical murine model of reversible bile duct ligation that is more physiologic than prior models of bile duct ligation reversal. Our model demonstrates acute hepatic injury from 7 ‐day bile duct ligation with rapid improvement after restoration of bile flow, including changes in immune, bile acid, and fibrotic pathways during this response. Further studies with this model may identify novel therapeutic targets for pediatric and adult cholestatic liver disease. AbstractThere are limited murine models of cholestatic liver diseases characterized by chronic biliary obstruction and resumption of bile flow. While murine bile duct ligation (BDL) is a well ‐established model of obstructive cholestasis, current models of BDL reversal (BDLR) alter biliary anatomy. We aimed to develop a more physiologic model of BDLR to evaluate the time course and mechanism for resolution of hepatic injury after biliary obstruction. In the present study, we restored b ile flow into the duodenum without disruption of the gall bladder after murine BDL using biocompatible PE‐50 tubing. After establishing the technique, overall survival for BDLR at 7 or 14 days after BDL was 88%. Sham laparotomy was performed in control mice. Laboratory data, liver histology, and hepatic gene expression were compared among BDL, BDLR, and controls. Laboratory evidence of cholestatic liver injury was observed at day 7 after BDL and rapid improvement occurred within 48 hr of BDLR. After BD...
Source: Physiological Reports - Category: Physiology Authors: Tags: ORIGINAL RESEARCH Source Type: research