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Mechanism of the cardioprotection of rhEPO pretreatment on suppressing the inflammatory response in ischemia-reperfusion
Liu,Xiaoming1; Xie,Weiying1; Liu,Pichu2; Duan,Manlin1; Jia,Zhen1; Li,Wei1; Xu,Jianguo1
2006-04-04
Source PublicationLife Sciences
ISSN00243205
Volume78Issue:19Pages:2255-2264
AbstractErythropoietin (EPO), originally known for its role in stimulation of erythropoiesis, has recently been shown to have a dramatic protective effect in animal models of myocardial ischemia-reperfusion (I-R) injury. However, the precise mechanisms remain unclear. We tried to study the anti-inflammatory properties of recombinant human erythropoietin (rhEPO) using an in vivo myocardial I-R rat model, which was established by 30 min ligation of left descending coronary and 3 h reperfusion. rhEPO or saline solution was intraperitoneally injected 24 h before I-R insult. The infarct size was measured by triphenyltetrazolium chloride (TTC)-Evans blue technique. Myeloperoxidase (MPO) activity and tissue neutrophil infiltration were studied. Ultrastructural organizations were observed and semiquantitatively evaluated. Tumor necrosis-alpha (TNF-α), interleukin-6 (IL-6), and IL-10 concentrations of left ventricle were analyzed by enzyme-linked immunosorbance assays; intercellular adhesion molecule-1 (ICAM-1) by reverse-transcription polymerase chain reaction; and nuclear factor-kappa B (NF-κB) and activator protein 1 (AP-1) by electrophoretic mobility shift assay, respectively. We found that a single bolus injection of 5000 units/kg of rhEPO 24 h before insult remarkably reduced infarct size and neutrophil infiltration. It greatly attenuated I-R-induced NF-κB and AP-1 activation with decreased TNF-α, IL-6, and ICAM-1 production, but enhanced IL-10 production. In conclusion, the cardioprotection of EPO may be due in part to the suppression of the inflammatory response via down-regulation of NF-κB and AP-1 induced by I-R. IL-10 was also suggested to play a protective role through another independent mechanism involved in cardioprotection of rhEPO. © 2005 Elsevier Inc. All rights reserved.
KeywordAP-1 Erythropoietin IL-10 Ischemia-reperfusion NF-κB
DOI10.1016/j.lfs.2005.09.053
URLView the original
Language英语
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Cited Times [WOS]:75   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionPersonal research not belonging to the institution
Affiliation1.Department of Anesthesiology,Jinling Hospital,Nanjing University,,China
2.Department of Surgery,Jinling Hospital,Nanjing University,,China
Recommended Citation
GB/T 7714
Liu,Xiaoming,Xie,Weiying,Liu,Pichu,et al. Mechanism of the cardioprotection of rhEPO pretreatment on suppressing the inflammatory response in ischemia-reperfusion[J]. Life Sciences,2006,78(19):2255-2264.
APA Liu,Xiaoming.,Xie,Weiying.,Liu,Pichu.,Duan,Manlin.,Jia,Zhen.,...&Xu,Jianguo.(2006).Mechanism of the cardioprotection of rhEPO pretreatment on suppressing the inflammatory response in ischemia-reperfusion.Life Sciences,78(19),2255-2264.
MLA Liu,Xiaoming,et al."Mechanism of the cardioprotection of rhEPO pretreatment on suppressing the inflammatory response in ischemia-reperfusion".Life Sciences 78.19(2006):2255-2264.
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