OXIDATIVE STRESS AND ATHEROSCLEROTIC 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，部分原因是电流的限制 评估体内自由基生成的方法学。现在 研究将利用气相色谱/质谱仪(GC/MS)方法 对于两个结构不同的F2-异前列烷的测定，8-epi- PGF2a-I。这些自由基催化脂质的新标记物 体内过氧化作用将与低密度脂蛋白一起进行评估 氧化性和内皮血管舒缩功能，以解决 糖尿病和糖尿病患者氧化应激增强的假说 这先于微血管或大血管疾病的发生。尿液 类风湿性关节炎患者的F2-异前列腺素排泄量 1糖尿病伴和不伴视网膜病变；在2型患者中 有或没有大血管疾病的糖尿病患者； 非糖尿病起源的外周血管病变 控制。因为异前列腺素是由花生四烯酸原位生成的 酯化成磷脂，我们将分离出低密度脂蛋白来测量程度 低密度脂蛋白磷脂含有8-epi-PGF2a和IPF2a-I。我们会 还评估了低密度脂蛋白对氧化的敏感性和 铜诱导氧化过程中低密度脂蛋白中F2-异前列腺素的形成。 内皮依赖性和非内皮依赖性的血管扩张 将采用高分辨率、无创的方法测量肱动脉 血管抗氧化剂，维生素E+C，将抑制尿液中 F2-异前列腺素对低密度脂蛋白易感性的调节作用 内皮血管舒缩功能的氧化和恢复。这个 这项研究的结果可能支持这样的假设： 糖尿病的氧化应激反应先于血管病变 并发症，并可能表明抗氧化剂的治疗作用 补充其他治疗方法以预防或 改善糖尿病并发症。

The role of oxidative stress in the evolution of diabetic vascular complications is unclear, in part due to limitation of current methodology to assess free radical generation in vivo. The present study will utilize gas chromatography/mass spectrometry (GC/MS) methods for the measurement of two structurally distinct F2-isoprostanes, 8-epi- PGF2a-I. These novel markers of free radical catalyzed lipid peroxidation in vivo will be assessed in conjunction with LDL oxidizability and endothelial vasomotor function to address the hypothesis that oxidative stress is enhanced in diabetes mellitus and that this precedes the onset of micro or macrovascular disease. Urinary excretion of the F2-Isoprostanes will be measured in patients with type 1 diabetes with and without retinopathy; in patients with type 2 diabetes with and without macrovascular disease; in patients with peripheral vascular disease of non-diabetic origin and in appropriate controls. Because isoprostanes are formed in situ from arachidonic acid esterified to phospholipid, we will isolate LDL to measure the degree to which LDL phospholipids contain 8-epi-PGF2a and IPF2a-I. We will also assess the LDL susceptibility to oxidation and the time course of formation of F2-Isoprostanes in the LDL during copper-induced oxidation. Endothelial-dependent and endothelial-independent dilatation of the brachial artery will be measured by high-resolution, non-invasive vascular antioxidants, vitamins E+C, will depress urinary excretion of F2-Isoprostanes concomitantly with modulation of LDL susceptibility to oxidation and restoration of endothelial vasomotor function. The results of this study might support the hypothesis that increased oxidative stress in diabetes precedes the onset of vascular complications and might indicate a therapeutic role for antioxidants in complementing other therapeutic approaches to the prevention or amelioration of diabetic complications.