Unité Propre de Recherche de l'Enseignement Supérieur Equipe d'Accueil, Protection et Remodelage du Myocarde, Faculté de Médecine d'Angers, Université d'Angers, Service de Cardiologie, Centre Hospitalier Universitaire d'Angers, Angers Cedex 1, France.
Am J Physiol Heart Circ Physiol. 2009 Dec;297(6):H2035-43. doi: 10.1152/ajpheart.00472.2009. Epub 2009 Jul 17.
Ischemic postconditioning (IPost) and erythropoietin (EPO) have been shown to attenuate myocardial reperfusion injury using similar signaling pathways. The aim of this study was to examine whether EPO is as effective as IPost in decreasing postischemic myocardial injury in both Langendorff-isolated-heart and in vivo ischemia-reperfusion rat models. Rat hearts were subjected to 25 min ischemia, followed by 30 min or 2 h of reperfusion in the isolated-heart study. Rats underwent 45 min ischemia, followed by 24 h of reperfusion in the in vivo study. In both studies, the control group (n=12; ischemia-reperfusion only) was compared with IPost (n=16; 3 cycles of 10 s reperfusion/10 s ischemia) and EPO (n=12; 1,000 IU/kg) at the onset of reperfusion. The following resulted. First, in the isolated hearts, IPost or EPO significantly improved postischemic recovery of left ventricular developed pressure. EPO induced better left ventricular developed pressure than IPost at 30 min of reperfusion (73.18+/-10.23 vs. 48.11+/-7.92 mmHg, P<0.05). After 2 h of reperfusion, the infarct size was significantly lower in EPO-treated hearts compared with IPost and control hearts (14.36+/-0.60%, 19.11+/-0.84%, and 36.21+/-4.20% of the left ventricle, respectively; P<0.05). GSK-3beta phosphorylation, at 30 min of reperfusion, was significantly higher with EPO compared with IPost hearts. Phosphatidylinositol 3-kinase and ERK1/2 inhibitors abolished both EPO- and IPost-mediated cardioprotection. Second, in vivo, IPost and EPO induced an infarct size reduction compared with control (40.5+/-3.6% and 28.9+/-3.1%, respectively, vs. 53.7+/-4.3% of the area at risk; P<0.05). Again, EPO decreased significantly more infarct size and transmurality than IPost (P<0.05). In conclusion, with the use of our protocols, EPO showed better protective effects than IPost against reperfusion injury through higher phosphorylation of GSK-3beta.
缺血后处理（IPost）和促红细胞生成素（EPO）已被证明通过相似的信号通路减轻心肌再灌注损伤。本研究的目的是检验 EPO 是否与 IPost 一样有效，可减少 Langendorff 分离心脏和在体缺血再灌注大鼠模型中的缺血后心肌损伤。在分离心脏研究中，大鼠心脏经历 25 分钟缺血，随后进行 30 分钟或 2 小时的再灌注。在体内研究中，大鼠经历 45 分钟缺血，随后进行 24 小时的再灌注。在这两项研究中，对照组（n=12；仅缺血再灌注）与再灌注时开始给予 IPost（n=16；3 个 10 秒再灌注/10 秒缺血循环）和 EPO（n=12；1000 IU/kg）进行比较。结果如下。首先，在分离的心脏中，IPost 或 EPO 显著改善了缺血后左心室发展压的恢复。EPO 在 30 分钟再灌注时诱导的左心室发展压优于 IPost（73.18+/-10.23 对 48.11+/-7.92mmHg，P<0.05）。2 小时再灌注后，与 IPost 和对照组相比，EPO 治疗的心脏梗死面积显著降低（分别为左心室的 14.36+/-0.60%、19.11+/-0.84%和 36.21+/-4.20%；P<0.05）。再灌注 30 分钟时，GSK-3β磷酸化与 EPO 相比在 IPost 心脏中明显更高。PI3K 和 ERK1/2 抑制剂消除了 EPO 和 IPost 介导的心脏保护作用。其次，在体研究中，与对照组相比，IPost 和 EPO 诱导的梗死面积减小（分别为 40.5+/-3.6%和 28.9+/-3.1%，风险面积的 53.7+/-4.3%；P<0.05）。同样，EPO 比 IPost 显著减少更多的梗死面积和透壁性（P<0.05）。总之，使用我们的方案，EPO 通过更高的 GSK-3β磷酸化显示出比 IPost 更好的抗再灌注损伤保护作用。
