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Erythropoietin attenuates ischemia-reperfusion induced lung injury by inhibiting tumor necrosis factor-alpha and matrix metalloproteinase-9 expression.
Eur J Pharmacol. 2009 Jan 14; 602(2-3):406-12.EJ

Abstract

Erythropoietin (Epo) was recently defined as an endogenous agent with more than hematopoietic functions. Previously we explored the potential of this agent to ameliorate lung ischemia-reperfusion (I/R) injury. The present study aims to determine the optimal dose and timing of administration for improving lung injury, and to further investigate the mechanisms by which Epo ameliorates lung I/R injury. The left lungs of Sprague-Dawley rats underwent 90 min ischemia and 120 min reperfusion. Firstly, animals in different groups were intraperitoneally injected with various doses of recombined human erythropoietin (rhEpo) 24 h prior to operation, 2 h prior to operation, or after the onset of reperfusion. Pulmonary myeloperoxidase (MPO) activity and malondialdehyde (MDA) content were evaluated. Treatment with 3 KU/kg rhEpo 2 h prior to operation was optimal for attenuating pulmonary MPO activity and MDA content. With such treatment, ultrastructural changes of pneumocytes were observed, and the pneumocyte apoptosis index was also determined by terminal dUTP nick-end labeling method. The plasma concentrations of tumor necrosis factor (TNF)-alpha and matrix metalloproteinase (MMP)-9 were evaluated by enzyme-linked immunosorbent assay, and pulmonary expression by immunohistochemistry. When pretreated with rhEpo, the pneumocyte ultrastructure was predominantly maintained and the pulmonary apoptosis index was markedly reduced. In comparison with untreated animals, in treated animals the plasma concentrations of TNF-alpha and MMP-9 were significantly decreased, and their expression in lung tissue was markedly reduced as well. The results indicated that Epo potently protected against lung I/R injury by inhibiting systemic and local expression of TNF-alpha and MMP-9.

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Publisher Full Text (DOI)

Authors+Show Affiliations

Wu H
Department of Cardiothoracic Surgery, Jingling Hospital, Clinical Medicine School of Nanjing University, Nanjing, China.
Dong G
No affiliation info available
Liu H
No affiliation info available
Xu B
No affiliation info available
Li D
No affiliation info available
Jing H
No affiliation info available

MeSH

AnimalsApoptosisDose-Response Relationship, DrugErythropoietinGene Expression RegulationLung InjuryMaleMalondialdehydeMatrix Metalloproteinase 9PeroxidasePulmonary AlveoliRatsRats, Sprague-DawleyReperfusion InjuryTime FactorsTumor Necrosis Factor-alpha

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19061883

Citation

Wu, Haiwei, et al. "Erythropoietin Attenuates Ischemia-reperfusion Induced Lung Injury By Inhibiting Tumor Necrosis Factor-alpha and Matrix Metalloproteinase-9 Expression." European Journal of Pharmacology, vol. 602, no. 2-3, 2009, pp. 406-12.
Wu H, Dong G, Liu H, et al. Erythropoietin attenuates ischemia-reperfusion induced lung injury by inhibiting tumor necrosis factor-alpha and matrix metalloproteinase-9 expression. Eur J Pharmacol. 2009;602(2-3):406-12.
Wu, H., Dong, G., Liu, H., Xu, B., Li, D., & Jing, H. (2009). Erythropoietin attenuates ischemia-reperfusion induced lung injury by inhibiting tumor necrosis factor-alpha and matrix metalloproteinase-9 expression. European Journal of Pharmacology, 602(2-3), 406-12. https://doi.org/10.1016/j.ejphar.2008.11.037
Wu H, et al. Erythropoietin Attenuates Ischemia-reperfusion Induced Lung Injury By Inhibiting Tumor Necrosis Factor-alpha and Matrix Metalloproteinase-9 Expression. Eur J Pharmacol. 2009 Jan 14;602(2-3):406-12. PubMed PMID: 19061883.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Erythropoietin attenuates ischemia-reperfusion induced lung injury by inhibiting tumor necrosis factor-alpha and matrix metalloproteinase-9 expression. AU - Wu,Haiwei, AU - Dong,Guohua, AU - Liu,Hao, AU - Xu,Biao, AU - Li,Demin, AU - Jing,Hua, Y1 - 2008/11/27/ PY - 2008/09/18/received PY - 2008/11/03/revised PY - 2008/11/18/accepted PY - 2008/12/9/pubmed PY - 2009/3/31/medline PY - 2008/12/9/entrez SP - 406 EP - 12 JF - European journal of pharmacology JO - Eur J Pharmacol VL - 602 IS - 2-3 N2 - Erythropoietin (Epo) was recently defined as an endogenous agent with more than hematopoietic functions. Previously we explored the potential of this agent to ameliorate lung ischemia-reperfusion (I/R) injury. The present study aims to determine the optimal dose and timing of administration for improving lung injury, and to further investigate the mechanisms by which Epo ameliorates lung I/R injury. The left lungs of Sprague-Dawley rats underwent 90 min ischemia and 120 min reperfusion. Firstly, animals in different groups were intraperitoneally injected with various doses of recombined human erythropoietin (rhEpo) 24 h prior to operation, 2 h prior to operation, or after the onset of reperfusion. Pulmonary myeloperoxidase (MPO) activity and malondialdehyde (MDA) content were evaluated. Treatment with 3 KU/kg rhEpo 2 h prior to operation was optimal for attenuating pulmonary MPO activity and MDA content. With such treatment, ultrastructural changes of pneumocytes were observed, and the pneumocyte apoptosis index was also determined by terminal dUTP nick-end labeling method. The plasma concentrations of tumor necrosis factor (TNF)-alpha and matrix metalloproteinase (MMP)-9 were evaluated by enzyme-linked immunosorbent assay, and pulmonary expression by immunohistochemistry. When pretreated with rhEpo, the pneumocyte ultrastructure was predominantly maintained and the pulmonary apoptosis index was markedly reduced. In comparison with untreated animals, in treated animals the plasma concentrations of TNF-alpha and MMP-9 were significantly decreased, and their expression in lung tissue was markedly reduced as well. The results indicated that Epo potently protected against lung I/R injury by inhibiting systemic and local expression of TNF-alpha and MMP-9. SN - 1879-0712 UR - https://www.unboundmedicine.com/medline/citation/19061883/Erythropoietin_attenuates_ischemia_reperfusion_induced_lung_injury_by_inhibiting_tumor_necrosis_factor_alpha_and_matrix_metalloproteinase_9_expression_ DB - PRIME DP - Unbound Medicine ER -