OXIDATIVE STRESS AND ATHEROSCLEROTIC COMPLICATIONS OF DIABETES

糖尿病的氧化应激和动脉粥样硬化并发症

• 批准号: 6113233
• 负责人: FRANCESCA CATELLA-LAWSON
• 金额: $ 2.51万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-12-01 至 1999-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6113233
• 关键词: ascorbate; atherosclerosis; clinical research; copper; diabetes mellitus; diabetic angiopathy; eicosanoids; free radicals; gas chromatography mass spectrometry; glycosylation; human subject; low density lipoprotein; medical complication; molecular pathology; oxidative stress; tocopherols; urinalysis

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.

氧化应激在糖尿病血管病变中的作用 并发症尚不清楚，部分原因是当前方法的局限性， 评估体内自由基生成。 本研究将利用天然气 色谱/质谱（GC/MS）方法用于测量两种 结构上不同的F2-异前列烷，8-表-PGF 2a-I。 这些新的标志 体内自由基催化的脂质过氧化将在 结合LDL氧化能力和内皮血管功能， 解决糖尿病中氧化应激增强的假设 并且这在微血管或大血管疾病发作之前。 尿 F2-异前列腺素的排泄将在1型糖尿病患者中测量。 糖尿病伴和不伴视网膜病变; 2型糖尿病伴 无大血管病变;外周血管病变患者 非糖尿病性疾病，并在适当的控制。 因为 异前列烷由花生四烯酸酯化原位形成， 磷脂，我们将分离LDL来测量LDL 磷脂含有8-epi-PGF 2a和IPF 2a-I。 我们还将评估LDL 对氧化的敏感性和形成的时间过程 F2-铜诱导氧化过程中LDL中的异前列烷。 肱动脉内皮依赖性和非内皮依赖性扩张 动脉将通过高分辨率、无创血管测量 抗氧化剂，维生素E+C，将抑制尿排泄的F2-异前列腺素 同时调节LDL对氧化的敏感性， 恢复内皮血管功能。 本研究结果 可能支持糖尿病患者氧化应激增加的假设 在血管并发症发作之前， 抗氧化剂在补充其他治疗方法中的作用 预防或改善糖尿病并发症。