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Artículo en Inglés | IMSEAR | ID: sea-24741

RESUMEN

BACKGROUND & OBJECTIVES: Erythropoietin (EPO), originally identified for its critical hormonal role in promoting erythrocyte survival and differentiation, has shown to a protective effect in myocardial ischaemia-reperfusion (I-R) injury in animal model. However, the precise mechanisms remain unclear. The objective of this study was to determine the roles of nuclear factor-kappa B (NF-kB) and associated cytokines induced by I-R in the cardioprotection by recombinant human erythropoietin (rhEPO). Morphopathological observations were also made on the ultrastructure of myocardial tissue. METHODS: Myocardial I-R rat model 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 sizes were measured by triphenyltetrazolium chloride (TTC)-Evans blue technique and ultrastructural organizations were observed by a transmission electron microscope. Tumour necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and IL-10 concentrations were analyzed by enzyme-linked immunosorbance assays and NF-kB by electrophoretic mobility shift assay. TNF-alpha and IL-6 mRNA expression were studied by the reverse-transcription polymerase chain reaction (RT-PCR). RESULTS: A single bolus injection of 5,000 units/kg of rhEPO 24 h before insult remarkably reduced infarct size and improved ultrastructural organization of I-R myocardium. It greatly suppressed TNF-alpha and IL-6 expression, but enhanced IL-10 production. It modestly activated NF-kB before I-R insult and markedly attenuated subsequent NF-kB activation during sustained I-R. INTERPRETATION & CONCLUSION: The suppression of proinflammatory cytokines expression may act by inhibiting NF-kB activation during I-R, but not by induction of IL-10. This might be one of the molecular mechanisms of rhEPO in cardioprotection. In addition, NF-kB was suggested to play a dual role in cardioprotective effects of rhEPO.


Asunto(s)
Análisis de Varianza , Animales , Citocinas/metabolismo , Cartilla de ADN , Ensayo de Cambio de Movilidad Electroforética , Ensayo de Inmunoadsorción Enzimática , Eritropoyetina/metabolismo , Precondicionamiento Isquémico Miocárdico/métodos , Masculino , Microscopía Electrónica de Transmisión , Daño por Reperfusión Miocárdica/metabolismo , Miocardio/ultraestructura , FN-kappa B/metabolismo , Ratas , Ratas Sprague-Dawley , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa
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