Department of Physiology, University of Toronto, Toronto, Ontario, M5S 1A8 Canada.
Atherosclerosis. 2012 Jun;222(2):375-81. doi: 10.1016/j.atherosclerosis.2012.03.021. Epub 2012 Mar 27.
Revascularization procedures used for treatment of atherosclerosis often result in restenosis. Resveratrol (RSV), an antioxidant with cardiovascular benefits, decreases neointimal formation after arterial injury by a mechanism that is still not fully clarified. Our main objective was to address the role of nitric oxide synthases (NOSes) and more specifically the endothelial-NOS (eNOS) isoform as a mediator of this effect. RSV (4 mg/kg/day, s.c.) alone or in combination with the NOS inhibitor N-nitro-L-arginine methyl ester (L-NAME) (2 mg/kg/day, s.c.) was given to Sprague-Dawley rats beginning at 3 days before arterial (carotid or aortic) injury. RSV reduced neointimal formation by 50% (P<0.01), decreased intimal cell proliferation by 37% (P<0.01) and reduced inflammatory markers such as PECAM and MMP-9 mRNA. These effects of RSV were all abolished by coadministration of l-NAME. Oral RSV (beginning at 5 days before arterial injury) reduced neointimal thickness after femoral wire injury in mice, however this effect was not observed in eNOS knockout mice. This is the first report of RSV decreasing neointimal cell proliferation and neointimal growth through an eNOS-dependent mechanism.
用于治疗动脉粥样硬化的血管重建手术通常会导致再狭窄。白藜芦醇（RSV）是一种具有心血管益处的抗氧化剂，通过一种尚未完全阐明的机制，可减少动脉损伤后的新生内膜形成。我们的主要目的是探讨一氧化氮合酶（NOSes），特别是内皮型一氧化氮合酶（eNOS）同工酶作为这种作用的介导物的作用。RSV（4mg/kg/天，皮下注射）单独或与 NOS 抑制剂 N-硝基-L-精氨酸甲酯（L-NAME）（2mg/kg/天，皮下注射）一起，于动脉（颈动脉或主动脉）损伤前 3 天开始给予 Sprague-Dawley 大鼠。RSV 使新生内膜形成减少 50%（P<0.01），内膜细胞增殖减少 37%（P<0.01），并降低了 PECAM 和 MMP-9 mRNA 等炎症标志物。L-NAME 的共同给药消除了 RSV 的这些作用。在动脉损伤前 5 天开始口服 RSV 可减少小鼠股动脉损伤后的新生内膜厚度，但在 eNOS 敲除小鼠中未观察到这种作用。这是 RSV 通过 eNOS 依赖性机制减少新生内膜细胞增殖和新生内膜生长的第一个报告。
