Mouse model of liver ischemia and reperfusion injury: method for studying reactive oxygen and nitrogen metabolites in vivo

Free Radic Biol Med. 2009 Jan 1;46(1):1-7. doi: 10.1016/j.freeradbiomed.2008.09.029. Epub 2008 Oct 10.


The mouse model of liver ischemia and reperfusion injury has proven to be valuable for our understanding of the role that reactive oxygen and nitrogen metabolites play in postischemic tissue injury. This methods paper provides a detailed protocol for inducing partial liver ischemia followed by reperfusion. Liver ischemia is induced in anesthetized mice by cross-clamping the hepatic artery and portal vein for varying lengths of time, resulting in deprivation of blood flow to approximately 70% of the liver. Restoration of blood flow to the ischemic lobes enhances superoxide production concomitant with a rapid and marked decrease in the bioavailability of nitric oxide, resulting in alterations in the redox state of the liver in favor of a more oxidative environment. This hepatocellular oxidative stress induces the activation of oxidant-sensitive transcription factors followed by the upregulation of proinflammatory cytokines and mediators that ultimately lead to liver injury. This model can be induced in any strain or sex of mouse and requires 1-2 months of practice to become proficient in the surgery and animal manipulation. The roles of various reactive metabolites of oxygen and nitrogen may be evaluated using genetically engineered mice as well as selective molecular, cellular, and/or pharmacological agents.

MeSH terms

  • Age Factors
  • Alanine Transaminase / blood
  • Alanine Transaminase / genetics
  • Animals
  • Animals, Inbred Strains
  • Biochemistry / methods
  • Disease Models, Animal*
  • Enzyme Activation
  • Liver / blood supply
  • Liver / enzymology*
  • Liver / pathology
  • Liver / surgery
  • Mice
  • Mice, Knockout
  • Nitric Oxide / genetics
  • Nitric Oxide / metabolism
  • Nitric Oxide Synthase Type III / metabolism
  • Protein Engineering
  • Reperfusion / instrumentation
  • Reperfusion / methods
  • Reperfusion Injury / blood
  • Reperfusion Injury / enzymology*
  • Reperfusion Injury / pathology
  • Species Specificity
  • Superoxide Dismutase
  • Superoxides / metabolism
  • Time Factors
  • Tumor Necrosis Factor-alpha / blood
  • Tumor Necrosis Factor-alpha / genetics


  • Tumor Necrosis Factor-alpha
  • Superoxides
  • Nitric Oxide
  • Nitric Oxide Synthase Type III
  • Sod3 protein, mouse
  • Superoxide Dismutase
  • superoxide dismutase 2
  • Alanine Transaminase