Related Experiment Video
Updated: Mar 2, 2026
Bile Duct Ligation in Mice: Induction of Inflammatory Liver Injury and Fibrosis by Obstructive Cholestasis
Published on: February 10, 2015
Cholecystokinin protects mouse liver against ischemia and reperfusion injury
Ying Zhang1, Jiali Zhu2, Long Guo2
1Department of Anesthesiology and Critical Care, Changhai Hospital, Second Military Medical University, 168 Changhai Road, Shanghai 200433, China; Department of Anesthesiology, Central Hospital of Jiading District, 1 Chengbai Road, Shanghai 201800, China.
Background:
Cholecystokinin (CCK), as a gastrointestinal hormone, has an important protective role against sepsis or LPS-induced endotoxic shock. We aim to address the role of CCK in hepatic ischemia followed by reperfusion (I/R) injury.
Materials And Methods:
A murine model of 60min partial hepatic ischemia followed by 6h of reperfusion was used in this study. CCK and CCKAR Levels in blood and liver were detected at 3h, 6h, 12h and 24h after reperfusion. Then the mice were treated with CCK or proglumide, a nonspecific CCK-receptor (CCK-R) antagonist. Mice were randomly divided into four groups as follows: (1) sham group, in which mice underwent sham operation and received saline; (2) I/R group, in which mice were subjected to hepatic I/R and received saline; (3) CCK group, in which mice were subjected to hepatic I/R and treated with CCK (400μg/kg); (4) proglumide group (Pro), in which mice underwent hepatic I/R and treated with proglumide (3mg/kg); CCK and proglumide were administrated via tail vein at the moment of reperfusion. Serum AST (sAST) and serum ALT (sALT) were determined with a biochemical assay and histological analysis were performed with hematoxylin-eosin (H&E). Cytokines (IL-1β, IL-6, IL-10, TNF-α) expressions in blood were determined with enzyme-linked immunosorbent assay (ELISA). The MPO (myeloperoxidase) assay were used to measure neutrophils' infiltration into the liver. The apoptotic index (TUNEL-positive cell number/total liver cell number×100%) was calculated to assess hepatocelluar apoptosis. Finally, activation of NF-κB and phosphor-p38 expression in liver homogenates were analyzed with Western Blot (WB).
Results:
Our findings showed that 1) CCK and CCK-AR were upregulated in our experimental model over time; 2) Treatment with CCK decreased sAST/sALT levels, inflammatory hepatic injury, neutrophil influx and hepatocelluar apoptosis, while proglumide aggravated hepatic injury.
Conclusion:
These findings support our hypothesis and suggest that CCK played a positive role in the ongoing inflammatory process leading to liver I/R injury.
