THE PHARMACOLOGY OF OMEGA-3 FATTY ACIDS IN MAN

许多临床研究正在进行中，以确定是否浓缩了 西式饮食中含有鱼油中的w-3脂肪酸将防止 动脉粥样硬化及其并发症的发展。这一概念是基于 关于高膳食摄入量人群的流行病学提示 这类脂肪酸(例如，爱斯基摩人和沿海的日本人)发病率很低 中风和心肌梗塞。这些数据被放大 研究发现，爱斯基摩人和食用鱼油的志愿者会长时间发育 出血时间和体外明显改变的血小板功能，因为 最近的证据有力地表明了慢性血小板激活的作用 而内皮细胞损伤在动脉粥样硬化的发生发展中起重要作用。很少 已经对鱼油(或二十碳五烯酸)的影响进行了研究 补充酸性物质(EPA)对血小板-血管相互作用指标的影响 准确反映体内前列腺素代谢的变化，或 它们评估了饮食中EPA增加对许多途径的影响 花生四烯酸(AA)在完整动物或人体内的代谢。自从美国环保署 补充可能会对拮抗AA产生不同的影响 代谢途径(如促凝集)血栓烷VS抗凝集 前列环素)改变前列腺素的净生物学结果 通过饮食方式的前体池是不可预测的。 我们建议评估饲喂w-3脂肪酸对体内的影响。 通过测量AA和EPA衍生前列腺素的排泄来产生前列腺素 鱼油饲养过程中尿液代谢产物的最新检测方法 以及研究白三烯和羟基脂肪酸的变化 新陈代谢通过这种喂养在人类细胞中诱导的新陈代谢在建立了 正常志愿者和无症状志愿者的生化变化 动脉粥样硬化症，我们将尝试评估生物功能的变化 研究补充EPA是否能降低患者的血压 动脉粥样硬化伴轻度未经治疗的高血压以及EPA是否 影响变应原致敏后早期或晚期的支气管反应 对过敏性哮喘患者的挑战。在这些新开发的研究中 毛细管柱气相色谱/负离子化学电离质谱法 用于评估气旋和气旋的类型和数量变化 体内释放的脂氧合酶产物和分离的细胞 EPA喂养后的志愿者。通过阐明丹参的临床药理作用 人类W-3脂肪酸与环氧合酶和脂氧合酶的关系 途径，可以开发临床应用的合理基础， 允许设计良好的临床研究评估其在 改变人类疾病的原因。

Many clinical studies are being carried out to see if enrichment of the Western diet with w-3 fatty acids found in fish oil will prevent the development of atherosclerosis and its complications. This notion is based on the epidemiologic suggestion that populations with a high dietary intake of such fatty acids (eg. Eskimos and coastal Japanese) have a low incidence of stroke and myocardial infarction. These data are amplified by the finding that Eskimos and volunteers who consume fish oil develop prolonged bleeding times and apparently altered platelet function ex vivo, since recent evidence strongly suggests a role for chronic platelet activation and endothelial damage in the development of atherosclerosis. Very few studies have been performed on the effects of fish oil (or eicosapentaenoic acid, EPA) supplementation on indices of platelet-vascular interactions which accurately reflect alterations in prostanoid metabolism in vivo, or which assess the effects of increased dietary EPA on the many pathways of arachidonic acid (AA) metabolism in intact animals or man. Since EPA supplementation probably will have different effects on antagonistic AA metabolic pathways (eg. proaggregatory) thromboxane vs antiaggregatory prostacyclin) the net biologic result of altering the prostaglandin precursor pool by dietary means is unpredictable. We propose to assess the effects of feeding w-3 fatty acids on in vivo production of AA and EPA derived prostanoids by measuring the excretion of urinary metabolites with state-of-the-art methods during fish oil feeding as well as to study alterations in leukotriene and hydroxy fatty acid metabolism induced in human cells by such feeding. After establishing the biochemical changes which take place in normal volunteers and asymptomatic atherosclerotics, we will attempt to assess changes in biologic function by investigating whether EPA supplementation lowers blood pressure in atherosclerotics with mild untreated hypertension and whether EPA influences the early or late phase bronchial responses after allergen challenge in allergic asthmatics. During these studies newly developed capillary column GC/negative ion chemical ionization MS methods will be employed to assess changes in the types and amounts of cyclo and lipoxygenase products released in vivo and by cells isolated from volunteers after EPA feeding. By clarifying the clinical pharmacology of w-3 fatty acids in man in regards to both the cyclo and lipoxygenase pathways, a rational basis for clinical applications can be developed, allowing well-designed clinical studies to assess their potential in modifying the cause of human disease.