Hepatocellular heme oxygenase-1: a potential mechanism of erythropoietin-mediated protection after liver ischemia-reperfusion injury

摘要

Hepatic ischemia-reperfusion (IR) results in progressive injury, initiated by oxidative stress during ischemia and compounded by cytokine-mediated inflammation during reperfusion. Recovery requires strict regulation of these events. Recombinant human erythropoietin (rhEPO) is thought to mitigate hepatocellular IR injury by altering the non-parenchymal liver microenvironment. This study sought to identify additional mechanisms whereby rhEPO is protective after liver IR injury.MethodsMice were treated with rhEPO (4units/gm SQ) at the onset of partial liver ischemia and assessed for transaminase and histologic injury at intervals after reperfusion. Induction of cytokines, activation of signal transducers and activators of transcription (STATs), suppressors of cytokine signaling (Socs1, Socs3, Cis), caspase-3 activation, and heme oxygenase-1 (HO-1) expression were assessed in post-ischemic liver. Effects of rhEPO stimulation were further characterized in whole liver lysates from mice undergoing rhEPO injection alone and in cultured AML-12 hepatocytes.