Pretreatment with erythropoietin reduces hepatic ischemia-reperfusion injury

Hepatobiliary Pancreat Dis Int. 2009 Jun;8(3):294-9.

Abstract

Background: During hepatectomy, a period of ischemia and restoration of the blood supply can result in hepatic ischemia-reperfusion injury (IRI). Current research indicates that erythropoietin (EPO) has a protective effect in animal models of cerebral ischemia, myocardial infarction, and renal IRI. However there is lack of research into the role of EPO in hepatic IRI. This study aimed to explore the role of EPO in hepatic IRI and its possible mechanism of action.

Methods: Thirty male Sprague-Dawley rats were divided into three groups: (1) ten rats in the experimental group were given 1000 IU/kg EPO one day before the operation; (2) ten rats in a control group were given normal saline preoperatively as a placebo; and (3) ten rats served as a sham-operated group. Hepatic IRI was induced by occluding the hepatic arteries of the three cephalad hepatic segments and the portal vein for about 45 minutes, while in the sham-operated group only laparotomy was performed. The levels of ALT and AST were tested 24 hours pre- and post-operation. All rats were sacrificed 24 hours after the operation to assess the pathologic changes in the liver and measure the expression of heme oxygenase-1 (HO-1) through Western blotting and RT-PCR.

Results: Hepatic IRI was markedly mitigated in the experimental group as compared with the control group. Moreover, the expression of HO-1 at the level of both transcription and protein increased prominently (P<0.05) in the experimental group.

Conclusion: These results demonstrate that EPO can up-regulate HO-1 in liver tissues and accordingly decrease hepatic injury through its anti-inflammatory property.

MeSH terms

  • Alanine Transaminase / blood
  • Animals
  • Aspartate Aminotransferases / blood
  • Blotting, Western
  • Erythropoietin / therapeutic use*
  • Heme Oxygenase-1 / genetics
  • Heme Oxygenase-1 / metabolism
  • Hepatectomy / adverse effects*
  • Liver / blood supply*
  • Liver / enzymology
  • Liver / pathology
  • Male
  • Postoperative Period
  • Preoperative Care*
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Reperfusion Injury / etiology*
  • Reperfusion Injury / prevention & control*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Up-Regulation

Substances

  • RNA, Messenger
  • Erythropoietin
  • Heme Oxygenase-1
  • Aspartate Aminotransferases
  • Alanine Transaminase