Burstein Brett, Maguy Ange, Clément Robert, Gosselin Hugues, Poulin Francine, Ethier Nathalie, Tardif Jean-Claude, Hébert Terence E, Calderone Angelino, Nattel Stanley
Research Center, Montreal Heart Institute and Université de Montréal, Montreal, Quebec, Canada.
J Pharmacol Exp Ther. 2007 Dec;323(3):916-23. doi: 10.1124/jpet.107.127548. Epub 2007 Sep 17.
Resveratrol (RES; trans-3,5,4'-trihydroxystilbene) has been shown to improve health and slow the progression of disease in various models. Several cardioprotective mechanisms have been identified including antioxidant, anti-inflammatory, and antifibrotic actions. Each of these actions is thought to have the ability to attenuate the pathophysiology underlying the deleterious cardiac structural remodeling that results from acute myocardial infarction (MI). Therefore, we evaluated the effect of resveratrol treatment on the progression of cardiac remodeling after MI. Four groups of rats (sham, n = 6; sham + RES, n = 21; MI, n = 26; MI + RES, n = 24) were treated for 13 weeks, starting 7 days before ligation of the left anterior descending coronary artery. Serial transthoracic echocardiography revealed that resveratrol had no effect on MI-induced left-ventricular and left-atrial dilatation or reduction in left-ventricular fractional shortening. Consistent with these findings, resveratrol did not improve the deterioration of hemodynamic function or reduce infarct size at 12 weeks post-MI. Resveratrol-treated animals did, however, show preserved cardiac contractile reserve in response to dobutamine administration. Radioligand binding revealed that MI reduced beta-adrenergic receptor density. Resveratrol administration increased beta-adrenoceptor density, so that resveratrol-treated MI rats had beta-adrenoceptor densities similar to normal rats. Real-time reverse transcription-polymerase chain reaction revealed that MI-induced changes in sarcoplasmic reticulum Ca2+-ATPase 2 and transforming growth factor beta-1 expression were unaltered by resveratrol, whereas MI-induced increases in atrial natriuretic factor (ANF) and connective tissue growth factor (CTGF) expression were attenuated. Resveratrol treatment does not improve cardiac remodeling and global hemodynamic function post-MI but does preserve contractile reserve and attenuate ANF and CTGF up-regulation.
白藜芦醇（RES；反式-3,5,4'-三羟基茋）已被证明在多种模型中可改善健康状况并减缓疾病进展。已确定了几种心脏保护机制，包括抗氧化、抗炎和抗纤维化作用。这些作用中的每一种都被认为有能力减轻急性心肌梗死（MI）导致的有害心脏结构重塑的病理生理学过程。因此，我们评估了白藜芦醇治疗对心肌梗死后心脏重塑进展的影响。四组大鼠（假手术组，n = 6；假手术+白藜芦醇组，n = 21；心肌梗死组，n = 26；心肌梗死+白藜芦醇组，n = 24）从左冠状动脉前降支结扎前7天开始接受为期13周的治疗。连续经胸超声心动图显示，白藜芦醇对心肌梗死诱导的左心室和左心房扩张或左心室缩短分数降低没有影响。与这些发现一致，白藜芦醇在心肌梗死后12周并未改善血流动力学功能的恶化或减小梗死面积。然而，接受白藜芦醇治疗的动物在给予多巴酚丁胺后显示出保留的心脏收缩储备。放射性配体结合显示心肌梗死降低了β-肾上腺素能受体密度。给予白藜芦醇增加了β-肾上腺素能受体密度，因此接受白藜芦醇治疗的心肌梗死大鼠的β-肾上腺素能受体密度与正常大鼠相似。实时逆转录-聚合酶链反应显示，白藜芦醇未改变心肌梗死诱导的肌浆网Ca2+-ATP酶2和转化生长因子β-1表达的变化，而心肌梗死诱导的心房利钠因子（ANF）和结缔组织生长因子（CTGF）表达的增加则被减弱。白藜芦醇治疗不能改善心肌梗死后的心脏重塑和整体血流动力学功能，但确实保留了收缩储备并减弱了ANF和CTGF的上调。
