ESTROGEN & VIT E ON NITRIC OXIDE & INFLAMMATION IN POSTMENOPAUSAL WOMEN

人类的动脉粥样硬化与炎症有关。提高一氧化氮(NO)生物活性的治疗可能通过抑制靶基因的转录激活来减少血管壁内促炎症蛋白的合成。由于雌激素和维生素E治疗改善了内皮细胞的NO生物活性，我们使用结合马雌激素(CEE)。每天625毫克，每天维生素E 800IU，以及这两种药物的组合，在一项随机、双盲、三期交叉研究中，对28名绝经后妇女进行了6周的治疗。分别于治疗前后测定前臂缺血后肱动脉血流介导性扩张(FMD)和血清炎症细胞黏附分子E-选择素、细胞间黏附分子(ICAM-1)和血管细胞黏附分子(VCAM-1)水平。所有治疗都改善了FMD(均为P&lt；0.001)，且改善程度相似(经方差分析，P=0.267)，但对硝酸甘油的扩张器反应无明显改善(均为P&t；0.235)。然而，只有包括CEE在内的疗法才能显著降低细胞黏附分子的水平。与各自的基线值相比，CEE(-13+/-15%，p&lt；0.001)、CEE与维生素E联合(-20+/-17%，p&lt；0.001)的E-选择素水平降低，但不是单独维生素E(+3+/-28%)。CEE(-7+/-17%，p&lt；0.05)、CEE与维生素E(-7+/-19%，p&lt；0.05)联合应用可降低ICAM-1水平，但不能单独应用维生素E。CEE联合维生素E(-2+/-21%)或单独使用维生素E(-3+/-14%)均不能降低血管细胞黏附分子-1的水平(P&lt；0.001)，差异有高度显著性(P&lt；0.01)。我们的结论是，改善血管内皮细胞NO的治疗对血管炎症标志物的影响可能不同，这表明绝经后女性雌激素的主要抗炎机制。-动脉粥样硬化、一氧化氮、马结合雌激素、血流介导的扩张、细胞间黏附分子、血管细胞黏附分子-人类受试者

Atherosclerosis in humans is associated with inflammation. Therapies that increase nitric oxide (NO) bioactivity may reduce synthesis of proinflammatory proteins within the vessel wall by inhibiting transcriptional activation of target genes. As estrogen and vitamin E therapies improve endothelial NO bioactivity, we administered conjugated equine estrogen (CEE) .625 mg daily, vitamin E 800 IU daily, and the combination, each for 6 weeks to 28 postmenopausal women in a randomized, double-blind , 3-period crossover study. Brachial artery flow-mediated dilation (FMD) following forearm ischemia (a bioassay for endothelial NO), and serum levels of inflammatory cell adhesion molecules E-selectin, intercellular adhesion molecule (ICAM-1), and vascular cell adhesion molecule (VCAM-1) were measured before and after each therapy. All therapies improved FMD (all P<0.001) and to a similar degree (P=0.267 by ANOVA), but not the dilator response to nitroglycerin (all P>0.235). However, only therapies including CEE significantly reduced levels of cell adhesion molecules. Compared with respective baseline values, levels of E-selectin were lowered on CEE (- 13+/-15%, p<0.001), CEE combined with vitamin E (-20+/-17%, p<0.001), but not vitamin E alone (+3+/-28%). Levels of ICAM-1 were lowered by CEE (-7+/-17%, p<.05), CEE combined with vitamin E (-7+/-19%, p<0.05), but not vitamin E alone. Levels of VCAM-1 were lowered by CEE (-6+/- 21%, p<0.01), but not by CEE combined with vitamin E (-2+/-21%), or vitamin E alone (-3+/-14%).Differences among therapies were highly significant for E-selectin (P<0.001 by ANOVA). We conclude that therapies that improve endothelial NO may not have comparable effects on markers of vascular inflammation, suggesting a primary anti- inflammatory mechanism for estrogen in postmenopausal women. - atherosclerosis, nitric oxide, conjugated equine estrogen, flow- mediated dilation, intercellular adhesion molecule, vascular cell adhesion molecule - Human Subjects