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 一类前列腺素异构体，在自由基催化下形成 花生四烯酸的方式，最初在磷脂中酯化， 它们被磷脂酶切割。 F2的定量方法 异前列烷，8-epi-PGF 2 α，使用气相色谱/质谱法 (GC/MS），将被用来解决氧化应激的假设， 在糖尿病中增强，这先于微或 大血管疾病 尿8-epi-PGF 2 α和二烯结合物 比率，将在有和没有视网膜病变的糖尿病患者中测量， 并且没有大血管疾病和适当的控制。 解决 糖尿病患者LDL的氧化可能是由 高级糖基化终产物（AGEs）的积累，我们将 分离LDL以获得酯化8-epi-PGF 2 α和apo-B-和lipid- 联系AGEs 此外，在这些科目中，我们将访问编队 LDL中的酯化异前列烷在体外氧化， 铜 最后，我们将讨论的假设，慢性 抗氧化剂，维生素E和C的管理，将抑制尿 8-epi-PGF 2 α伴随着对LDL易变性的调节， 氧化 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信息 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 esterfied 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 precededes 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 esterfied 8-epi-PGF2alpha and both apo-B- and lipid- linked AGEs. Additionally, in these subjects we will access the formation of esterfied 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 preceeds 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 potenial role of vitamin E and C antioxidant drugs in diabetes.