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Cyclooxygenase-2 plays an essential part in cardioprotection of delayed phase of recombinant human erythropoietin preconditioning in rats
  1. X Liu,
  2. Z Zhou,
  3. X Feng,
  4. Z Jia,
  5. Y Jin,
  6. J Xu
  1. Department of Anaesthesiology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, Jiangsu Province, China
  1. Correspondence to:
 Dr J Xu
 Department of Anaesthesiology, Jinling Hospital, 305 East Zhongshan Road, Nanjing, China; brightlxm{at}gmail.com

Abstract

Aims: To study the cardioprotection of recombinant human erythropoietin (rhEPO) preconditioning (EPC) and to investigate the role and possible mechanism of cyclooxygenase (COX)-2 in the delayed phase of EPC.

Methods: In phase 1, myocardial ischaemia reperfusion (I-R) rat model was established by 30 minutes ligation of left descending coronary and three hours of reperfusion. Rats were given 0.9% saline solution or rhEPO 24 hours before I-R protocol. COX-2 selective inhibitor celecoxib was given for further investigation of the cardioprotection of EPC. At the end of I-R protocol, infarct sizes were measured and ultrastructural organisations were studied. In phase 2, myocardial COX-2 mRNA expressions and prostaglandins (PGs) contents were studied in different groups after euthanasia.

Results: It was found that EPC could elicit potent cardioprotection against I-R injury, shown by reduction of infarct size and improvement of ultrastructural organisation; whereas administration of celecoxib resulted in complete loss of this protection. EPC resulted in robust increase in COX-2 mRNA and PGs levels that were also abrogated by celecoxib.

Conclusions: COX-2 plays an essential part in cardioprotection of the delayed phase of EPC in rats, which might be related to actions of PGE2 or PGI2, or both.

  • EPO, erythropoietin
  • rhEPO, recombinant human erythropoietin
  • EPC, erythropoietin preconditioning
  • COX, cyclooxygenase
  • PG, prostaglandin
  • AA, arachidonic acid
  • IPC, ischaemic preconditioning
  • RT-PCR, reverse transcription polymerase chain reaction
  • I-R, ischaemia reperfusion
  • PPC, pharmacological preconditioning
  • erythropoietin
  • myocardial ischaemia reperfusion
  • cyclooxygenase-2

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Footnotes

  • Funding: this work was supported by grants from Department of Anaesthesiology, Jinling Hospital of China.

  • Conflicts of interest: none declared.

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