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The effect of hepatic ischemia reperfusion injury in a murine model of nonalcoholic steatohepatitis. J Surg Res 2011 Jul;169(1):e7-14



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Scopus ID

2-s2.0-79958195503   10 Citations


BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) refers to an increasingly diagnosed condition involving triglyceride accumulation into hepatocytes resulting in a broad spectrum of liver injury. The progression of NAFLD, a relatively benign condition, to nonalcoholic steatohepatitis (NASH) involves the hepatic infiltration of inflammatory cells and subsequent hepatocellular injury. Ischemia/reperfusion (I/R) injury of the liver is a major complication of liver resection, hepatic trauma, and liver transplantation. To date, there have been no studies that have evaluated the effects of hepatic I/R on models of NASH.

OBJECTIVE: Evaluate the effects of hepatic I/R on a mouse model of NASH.

METHODS: A mouse model of progressive NASH was developed and evaluated using C57BL/6 mice fed a methionine choline deficient diet for 3, 6, 9, and 12 wk. Mice subsequently underwent 90 min of partial hepatic ischemia with reperfusion of 1, 4, and 8 h. Mice were sacrificed after the indicated periods, and blood and liver samples were taken for analysis.

RESULTS: Mice fed the MCD diet showed a rapid induction of hepatic steatosis, inflammation, and fibrosis by 3 wk that persisted over the 12-wk period of diet, as demonstrated by histologic examination, alanine aminotransferase (ALT), and liver content of myeloperoxidase (MPO). The response to I/R in livers with progressive NASH fed MCD diet for 3, 6, 9, and 12 wk showed marked neutrophil recruitment and hepatocyte necrosis.

CONCLUSION: These data suggest the inflammatory response from I/R is augmented in livers with NASH histopathology compared with normal liver.

Author List

Tevar AD, Clarke CN, Schuster R, Wang J, Edwards MJ, Lentsch AB


Callisia N. Clarke MD Assistant Professor in the Surgery department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Alanine Transaminase
Disease Models, Animal
Disease Progression
Fatty Liver
Mice, Inbred C57BL
Non-alcoholic Fatty Liver Disease
Reperfusion Injury