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

人类的动脉粥样硬化与炎症有关。增加一氧化氮（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蛋白的合成。由于雌激素和维生素E治疗可以改善内皮细胞NO的生物活性，我们使用了结合马雌激素（CEE）。每天625毫克，维生素E每天800国际单位，并结合，每6周对28名绝经后妇女进行随机，双盲，3期交叉研究。测量前臂缺血后肱动脉血流介导扩张（FMD）（内皮NO的生物测定），以及每次治疗前后炎症细胞粘附分子e -选择素、细胞间粘附分子（ICAM-1）和血管细胞粘附分子（VCAM-1）的血清水平。所有治疗均改善了FMD（均P<0.001），且改善程度相似（方差分析P=0.267），但没有改善扩张剂对硝酸甘油的反应（均P< 0.235）。然而，只有包括CEE在内的治疗才能显著降低细胞粘附分子的水平。与各自的基线值相比，CEE组E-选择素水平降低（- 13+/-15%,p<0.001）， CEE联合维生素E组E-选择素水平降低（-20+/-17%,p<0.001），但单独维生素E组E-选择素水平不降低（+3+/-28%）。CEE可降低ICAM-1水平（-7+/-17%,p<0.05）， CEE联合维生素E可降低ICAM-1水平（-7+/-19%,p<0.05），但单独维生素E不能降低ICAM-1水平。CEE可降低VCAM-1水平（-6+/- 21%,p<0.01），但CEE联合维生素E（-2+/-21%）或单独维生素E（-3+/-14%）均无显著性作用。e -选择素在治疗间的差异非常显著（方差分析P<0.001）。我们得出结论，改善内皮NO的治疗方法可能对血管炎症标志物没有类似的作用，这表明绝经后妇女雌激素的主要抗炎机制。-动脉粥样硬化，一氧化氮，共轭马雌激素，血流介导的扩张，细胞间粘附分子，血管细胞粘附分子-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