Cholecystokinin protects mouse liver against ischemia and reperfusion injury

Publication date: July 2017
Source:International Immunopharmacology, Volume 48
Author(s): Ying Zhang, Jiali Zhu, Long Guo, Yun Zou, Fang Wang, Han Shao, Jinbao Li, Xiaoming Deng
BackgroundCholecystokinin (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 methodsA 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).ResultsOur 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.ConclusionThese findings support our hypothesis and suggest that CCK played a positive role in the ongoing inflammatory process leading to liver I/R injury.



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