Kalakech Hussein, Hibert Pierre, Prunier-Mirebeau Delphine, Tamareille Sophie, Letournel Franck, Macchi Laurent, Pinet Florence, Furber Alain, Prunier Fabrice
L'UNAM Université, Angers, France; Université d'Angers, Laboratoire Cardioprotection, Remodelage et Thrombose, Angers, France.
L'UNAM Université, Angers, France; Université d'Angers, INSERM U771, CNRS UMR 6214, CHU Angers, Département de Biochimie et Génétique, Angers, France.
PLoS One. 2014 Sep 19;9(9):e107950. doi: 10.1371/journal.pone.0107950. eCollection 2014.
Recent findings indicate that apolipoprotein A-I (ApoA-I) may be a protective humoral mediator involved in remote ischemic preconditioning (RIPC). This study sought to determine if ApoA-I mediates its protective effects via the RISK and SAFE signaling pathways implicated in RIPC. Wistar rats were allocated to one of the following groups.
rats were subjected to myocardial ischemia/reperfusion (I/R) without any further intervention; RIPC: four cycles of limb I/R were applied prior to myocardial ischemia; ApoA-I: 10 mg/Kg of ApoA-I were intravenously injected prior to myocardial ischemia; ApoA-I + inhibitor: pharmacological inhibitors of RISK/SAFE pro-survival kinase (Akt, ERK1/2 and STAT-3) were administered prior to ApoA-I injection. Infarct size was significantly reduced in the RIPC group compared to CONTROL. Similarly, ApoA-I injection efficiently protected the heart, recapitulating RIPC-induced cardioprotection. The ApoA-I protective effect was associated with Akt and GSK-3β phosphorylation and substantially inhibited by pretreatment with Akt and ERK1/2 inhibitors. Pretreatment with ApoA-I in a rat model of I/R recapitulates RIPC-induced cardioprotection and shares some similar molecular mechanisms with those of RIPC-involved protection of the heart.
最近的研究结果表明，载脂蛋白A-I（ApoA-I）可能是参与远程缺血预处理（RIPC）的一种保护性体液介质。本研究旨在确定ApoA-I是否通过RIPC中涉及的RISK和SAFE信号通路介导其保护作用。将Wistar大鼠分为以下几组。
大鼠接受心肌缺血/再灌注（I/R），无进一步干预；RIPC组：在心肌缺血前进行四个周期的肢体I/R；ApoA-I组：在心肌缺血前静脉注射10mg/Kg的ApoA-I；ApoA-I +抑制剂组：在注射ApoA-I之前给予RISK/SAFE促生存激酶（Akt、ERK1/2和STAT-3）的药理抑制剂。与对照组相比，RIPC组的梗死面积显著减小。同样，注射ApoA-I可有效保护心脏，重现RIPC诱导的心脏保护作用。ApoA-I的保护作用与Akt和GSK-3β磷酸化有关，并被Akt和ERK1/2抑制剂预处理显著抑制。在I/R大鼠模型中用ApoA-I预处理可重现RIPC诱导的心脏保护作用，并与RIPC涉及的心脏保护作用具有一些相似的分子机制。
