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Mechanism of the cardioprotection of rhEPO pretreatment on suppressing the inflammatory response in ischemia-reperfusion.

机译:rhEPO预处理的心脏保护机制在缺血再灌注中抑制炎症反应。

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Erythropoietin (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-alpha), 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-kappaB) 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-kappaB and AP-1 activation with decreased TNF-alpha, 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-kappaB 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.
机译:促红细胞生成素(EPO)最初因其在刺激促红细胞生成中的作用而闻名,最近已显示出在心肌缺血再灌注(I-R)损伤的动物模型中具有显着的保护作用。但是,确切的机制仍不清楚。我们试图使用体内心肌I-R大鼠模型研究重组人促红细胞生成素(rhEPO)的抗炎特性,该模型是由左降冠状动脉结扎30分钟并再灌注3 h建立的。在I-R损伤前24小时腹膜内注射rhEPO或盐溶液。通过氯化三苯四唑(TTC)-伊文思蓝技术测量梗死面积。研究了髓过氧化物酶(MPO)活性和组织中性粒细胞浸润。观察超微结构并进行半定量评估。通过酶联免疫吸附试验分析左心室的肿瘤坏死-α(TNF-alpha),白介素-6(IL-6)和IL-10浓度;细胞间粘附分子-1(ICAM-1)通过逆转录聚合酶链反应;电泳迁移率变动分析分别检测核因子-κB(NF-κB)和激活蛋白1(AP-1)。我们发现,在损伤前24小时单次推注5000单位/ kg rhEPO可显着减少梗死面积和中性粒细胞浸润。它大大降低了I-R诱导的NF-κB和AP-1的激活,同时降低了TNF-α,IL-6和ICAM-1的产生,但增强了IL-10的产生。总之,EPO的心脏保护作用可能部分归因于I-R诱导的NF-κB和AP-1的下调,从而抑制了炎症反应。还建议IL-10通过参与rhEP​​O心脏保护的另一个独立机制发挥保护作用。

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