J Gu, Cq Wang, Hh Fan, Hy Ding, Xl Xie, Ym Xu, By Wang, Dj Huang
Department of Cardiology, Renji Hospital, affiliated to Shanghai Jiao-Tong University School of Medicine, Shanghai Blood Center, Shanghai, China.
J Cardiovasc Pharmacol. 2006 May;47(5):711-21. doi: 10.1097/01.fjc.0000211764.52012.e3.
The aim of this study was to investigate the effects of resveratrol on endothelial progenitor cell (EPC) activities in vitro and on the mobilization of circulating EPCs, and reendothelialization in balloon-injured aorta of rats. After being isolated, cultured, and characterized, human EPCs were stimulated with resveratrol. We found that a low concentration of resveratrol (1 microM) led to significant enhanced activities of proliferation, migration, and adhesion, as well as promoting endothelial nitric acid synthetase (eNOS) expression in EPCs, whereas a high concentration (60 microM) inhibited the aforementioned functions and eNOS expression. In a rat model of injured aorta, a low dosage of resveratrol (10 mg/kg) increased the amount of EPCs in rat circulation as compared with placebo, whereas the result of a high dosage (50 mg/kg) did not reach statistical difference. In addition, 10 mg/kg of resveratrol both accelerated reendothelialization and inhibited neointimal formation; however, 50 mg/kg only reduced neointimal formation, which was not as effective as the previous one. eNOS expression in injured arteries was potently enhanced in the 10 mg/kg group, but not in the 50 mg/kg group. These findings suggest that a low dosage of resveratrol could markedly raise the proliferative, migrative, and adhesive activities of EPCs and upgrade eNOS expression in vitro as well as increase EPC mobilization, enhance eNOS expression, and accelerate the repair of injured artery; however, a high dosage cannot.
本研究旨在探讨白藜芦醇对体外内皮祖细胞(EPC)活性、循环EPC动员以及大鼠球囊损伤主动脉再内皮化的影响。人EPC分离、培养并鉴定后,用白藜芦醇进行刺激。我们发现,低浓度白藜芦醇(1微摩尔)可显著增强EPC的增殖、迁移和黏附活性,并促进内皮型一氧化氮合酶(eNOS)表达,而高浓度(60微摩尔)则抑制上述功能及eNOS表达。在大鼠主动脉损伤模型中,低剂量白藜芦醇(10毫克/千克)与安慰剂相比可增加大鼠循环中EPC数量,而高剂量(50毫克/千克)的结果未达到统计学差异。此外,10毫克/千克白藜芦醇既加速了再内皮化又抑制了内膜形成;然而,50毫克/千克仅减少了内膜形成,效果不如前者。10毫克/千克组损伤动脉中的eNOS表达显著增强,而50毫克/千克组则未增强。这些发现表明,低剂量白藜芦醇可显著提高EPC的增殖、迁移和黏附活性,在体外提升eNOS表达,同时增加EPC动员、增强eNOS表达并加速损伤动脉修复;然而,高剂量则不能。