OXIDATIVE STRESS AND ANTHEROSCLEROTIC COMPLICATIONS OF DIABETES

氧化应激在糖尿病血管演变中的作用 并发症尚不清楚。这在一定程度上反映了电流的局限性 获取体内自由基生成的方法学。异戊二烯 是在自由基催化下形成的前列腺素异构体家族 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出来。一种新的定量化方法 气相色谱/质谱法测定F2异前列腺素8-epi-PGF2α 光谱分析(GC/MS)将被用来解决这样的假设 糖尿病患者的氧化应激反应增强，这在发病之前 微血管或大血管疾病。尿8-epi-PGF2α和二烯 结合率，将在糖尿病患者中进行测量 视网膜病变，有或没有大血管疾病，适当 控制。解决糖尿病患者体内低密度脂蛋白氧化的假说 可能是通过晚期糖基化末端的积累来促进的 产物(AGEs)，我们将分离低密度脂蛋白以获得酯化的8-epi-PGF2pha 以及载脂蛋白B和脂质相关的AGEs。此外，在这些科目中 我们将访问在低密度脂蛋白中形成的酯化异前列烷 在体外氧化，以响应铜。最后，我们将解决 假设长期服用抗氧化剂，维生素E &C，将在调节的同时降低尿8-epi-PGF2α 低密度脂蛋白对氧化的敏感性。 这些研究将通过一部小说提供第一批信息 人体体内自由基生成的定量方法 糖尿病。他们将解决这一假说，即增加氧化 应激反应先于临床可检测到的血管并发症的发生 而且它通过异前列腺素系统地反映在低密度脂蛋白中 队形。将获得有关潜在角色的初步信息 维生素E和C抗氧化剂在糖尿病中的应用。

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.