Vitamins C and E reduce retinal oxidative stress and nitric oxide metabolites and prevent ultrastructural alterations in porcine hypercholesterolemia
Vitamins C and E reduce retinal oxidative stress and nitric oxide metabolites and prevent ultrastructural alterations in porcine hypercholesterolemia
复制标题
DOI：
10.1167/iovs.04-0516
复制
发表时间：
2005-04-01
影响因子：
4.4
通讯作者：
Garcia-Layana, A
中科院分区：
文献类型：
--
作者：
Fernandez-Robredo, P;Moya, D;Garcia-Layana, A
目的。氧化应激被认为与年龄相关疾病的发病机制有关，如动脉粥样硬化和视网膜变性。本研究旨在检测猪高胆固醇血症模型的玻璃体视网膜氧化状态，以确定形态学改变并分析饲粮中补充维生素C和e的影响。分别饲喂标准饲料、高胆固醇饲料和添加维生素C和e的高胆固醇饲料，测定血浆中总胆固醇、甘油三酯、高密度脂蛋白、脂质过氧化和生育酚含量。测定玻璃体和视网膜匀浆中的脂质过氧化和一氧化氮（NO）代谢产物。用化学发光法分析了视网膜色素上皮（RPE）中超氧阴离子的释放。透射电镜观察视网膜形态。高胆固醇组视网膜氧化应激增加（P < 0.01），视网膜NO代谢产物增加（P < 0.05），超氧阴离子释放增加（P < 0.05）， RPE细胞内出现固缩、核膜不规则、脂质积聚和自噬细胞空泡。维生素C和E对rpe的生化变化和大部分超微结构改变具有抑制作用。结果表明，高胆固醇血症通过增加视网膜氧化应激和一氧化氮合成而不断演变，这可能导致视网膜超微结构改变。维生素C和E在视网膜组织中的有益作用进一步支持了这一假设。
PURPOSE. Oxidative stress is thought to be involved in the pathogenesis of age-related diseases, such as atherosclerosis and retinal degeneration. The current study was conducted to examine vitreoretinal oxidative status in a model of porcine hypercholesterolemia to identify morphologic alterations and analyze the effect of dietary supplementation with vitamins C and E.METHODS. Adult miniature pigs were fed standard chow, cholesterol-rich chow, or a cholesterol-rich diet supplemented with vitamins C and E. Total cholesterol, triglycerides, high-density lipoproteins, lipid peroxidation, and tocopherol were measured in plasma. Lipid peroxidation and nitric oxide ( NO) metabolites were measured in vitreous and retinal homogenates. Superoxide anion release in the retinal pigment epithelium (RPE) was analyzed by chemiluminescence. Retinal morphology was studied by transmission electron microscopy.RESULTS. The high-cholesterol group, with increased retinal oxidative stress ( P < 0.01) and NO metabolites in the retina ( P < 0.05), had increased superoxide anion release ( P < 0.05) and showed development of pyknosis, irregular nuclear membranes, and cytoplasmic accumulation of lipids and autophagocytic vacuoles in the RPE cells. Vitamins C and E prevented biochemical changes and most ultrastructural alterations in the RPE.CONCLUSIONS. The results suggest an evolving role for hypercholesterolemia through increased retinal oxidative stress and NO synthesis that could be responsible for retinal ultrastructural alterations. The beneficial effects of vitamins C and E in the retinal tissue further support this hypothesis.