OXIDATIVE STRESS AND ANTHEROSCLEROTIC COMPLICATIONS OF DIABETES

氧化应激在糖尿病血管病变中的作用 并发症尚不清楚。 这在一定程度上反映了当前的限制。 体内自由基生成的方法。 异甾烷 是前列腺素异构体家族，在自由基催化下形成， 以花生四烯酸的方式，最初在磷脂中酯化 它们被磷脂酶从其中切割。 的定量方法 F2异前列烷，8-epi-PGF 2 α，使用气相色谱/质谱法 将使用气相色谱/质谱法（GC/MS）来解决以下假设： 氧化应激在糖尿病中增强，并且这在发病之前 微血管或大血管疾病。尿8-epi-PGF 2 α和二烯 将在患有和不患有糖尿病的糖尿病患者中测量结合物比率。 视网膜病变，有和没有大血管疾病，并在适当的 对照 为了解决糖尿病中LDL氧化的假设， 可能是由于晚期糖基化末端的积累 产品（AGEs），我们将分离LDL以获得酯化的8-epi-PGF 2 α 以及载脂蛋白B和脂质连接的AGEs。 此外，在这些主题中， 我们将评估LDL中酯化异前列烷的形成， 在体外被铜氧化。 最后，我们将讨论 假设长期服用抗氧化剂、维生素E & C，将抑制尿8-epi-PGF 2 α伴随着调制 低密度脂蛋白易氧化性。 这些研究将提供第一个信息使用一本小说 人体内自由基生成的定量方法 糖尿病 他们将提出一个假设，即增加氧化 压力先于临床上可检测到的血管并发症的发生 并且它通过异前列腺素系统地和在LDL中反映 阵将获得关于潜在作用的初步资料 维生素E和C抗氧化药物在糖尿病中的应用

The role of the oxidant stress in the evolution of diabetic vascular complications is unclear. This reflects, in part, limitation of current methodology to access free radical generation in vivo. The isopstanes are a family of prostaglandin isomers formed in a free radical catalyzed manner from arachidonic acid, initially esterified in the phospholipid from which they are cleaved by phospholipases. A quantitative method for an F2 isoprostane, 8-epi-PGF2alpha, using gas chromatography / mass spectometry (GC/MS), will be utilized to address the hypothesis that oxidative stress is enhanced in diabetes and that this precedes the onset of micro or macrovascular disease. Urinary 8-epi-PGF2alpha and the diene conjugate ratio, will be measured in diabetics with and without retinopathy, with and without macrovascular disease and in appropriate controls. To address the hypothesis that oxidation of LDL in diabetes might be facilitated by accumulation of advanced glycosylation end products (AGEs), we will isolate LDL to access esterified 8-epi-PGF2alpha and both apo-B- and lipid-linked AGEs. Additionally, in these subjects we will access the formation of esterified isoprostanes in the LDL oxidized in vitro in response to copper. Finally, we will address the hypothesis that chronic administration of the antioxidants, vitamins E & C, will depress urinary 8-epi-PGF2alpha concomitantly with modulation of LDL susceptability to oxidation. These studies will provide the first information using a novel quantitative approach, on free radical generation in vivo in human diabetes. They will address the hypothesis that increased oxidative stress precedes the onset of clinically detectable vascular complications and that it is reflected both systematically and in LDL by isoprostane formation. Preliminary information will be obtained on the potential role of vitamin E and C antioxidant drugs in diabetes.