Several studies provide evidence that erythropoietin (EPO) could play an important role in the recovery of the heart subjected to ischemia–reperfusion. In this regard, it has been suggested that EPO could be involved in protein kinase B (Akt) activation as a cell survival protein. The aim of the present study was to investigate the effects of EPO on the Akt/glycogen synthase kinase 3 beta (GSK-3β) pathway in the presence or absence of wortmannin (W, Akt inhibitor) and its relationship with mitochondrial morphology and function preservation in ischemic-reperfused rat hearts. EPO improved the functional recovery of the heart subjected to ischemia–reperfusion, reduced the release of CK and the infarct size, and promoted preservation of the mitochondrial structure. Moreover, it reduced tissue lactate content and preserved glycogen in order to prevent ischemia. The results showed greater Akt activation, accompanied by preservation of swelling and mitochondrial calcium retention capacity, as well as an increase in ATP synthesis capacity. These results were accompanied by an inhibition of GSK-3β, suggesting regulation of Akt on the opening of the mitochondrial permeability transition pore. All these beneficial effects exerted by acute treatment with EPO were prevented by W. The present study provided novel evidence that EPO not only enhances intrinsic activation of Akt during myocardial ischemia–reperfusion but also promotes GSK-3β inhibition, contributing to mitochondrial structure and function preservation.

多项研究提供的证据表明，促红细胞生成素 (EPO) 在缺血再灌注心脏的恢复中发挥着重要作用。在这方面，有人认为 EPO 可能作为细胞存活蛋白参与蛋白激酶 B (Akt) 的激活。本研究的目的是研究在存在或不存在渥曼青霉素（W，Akt 抑制剂）的情况下 EPO 对 Akt/糖原合酶激酶 3 beta (GSK-3β) 通路的影响及其与线粒体形态和功能保存的关系在缺血再灌注大鼠心脏中。EPO改善了缺血再灌注后心脏的功能恢复，减少了CK的释放和梗塞面积，并促进了线粒体结构的保存。此外，它还降低组织乳酸含量并保留糖原以防止缺血。结果显示，Akt 激活程度更高，同时保留了肿胀和线粒体钙保留能力，以及 ATP 合成能力的增加。这些结果伴随着 GSK-3β 的抑制，表明 Akt 对线粒体通透性转换孔的开放进行调节。W 阻止了 EPO 急性治疗所发挥的所有这些有益作用。本研究提供了新的证据，表明 EPO 不仅增强心肌缺血再灌注期间 Akt 的内在激活，而且还促进 GSK-3β 抑制，有助于线粒体结构和功能的保存。