Phosphatidylinositol-3-kinase signaling is required for erythropoietin-mediated acute protection against myocardial ischemia/reperfusion injury
Phosphatidylinositol-3-kinase signaling is required for erythropoietin-mediated acute protection against myocardial ischemia/reperfusion injury
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DOI：
10.1161/01.cir.0000127954.98131.23
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发表时间：
2004-05-04
期刊：
影响因子：
37.8
通讯作者：
Semenza, GL
中科院分区：
文献类型：
--
作者：
Cai, ZQ;Semenza, GL
背景-大鼠肠外注射重组人促红细胞生成素（rhEPO）可诱导对24小时后心肌缺血/再灌注损伤的保护作用。然而，rhEPO介导的保护机制还没有determined.Methods和结果- rhEPO灌注到离体大鼠心脏超过15分钟前立即30分钟的无血流缺血和45分钟的再灌注。与生理盐水灌注的对照心脏相比，rhEPO灌注心脏的左室发展压力恢复增加。rhEPO还可增加AKT活性，减少细胞凋亡。所有这些影响被封锁时，磷脂酰肌醇-3-激酶抑制剂渥曼青霉素输注rhEPO.Conclusions - rhEPO提供即时保护，防止缺血/再灌注损伤的隔离灌注大鼠心脏，是由磷脂酰肌醇-3-激酶途径。
Background - Parenteral administration of recombinant human erythropoietin (rhEPO) to rats induces protection against myocardial ischemia/reperfusion injury 24 hours later. However, the mechanisms by which rhEPO mediates protection have not been determined.Methods and Results - rhEPO was perfused into isolated rat hearts over 15 minutes immediately before 30 minutes of no-flow ischemia and 45 minutes of reperfusion. Compared with saline-perfused control hearts, recovery of left ventricular developed pressure was increased in rhEPO-perfused hearts. rhEPO also increased AKT activity and decreased apoptosis. All of these effects were blocked when the phosphatidylinositol-3-kinase inhibitor wortmannin was infused with rhEPO.Conclusions - rhEPO provides immediate protection against ischemia/reperfusion injury in the isolated perfused rat heart that is mediated by the phosphatidylinositol-3-kinase pathway.