α-生育酚和芦丁对培养的内皮细胞中氧化型低密度脂蛋白诱导的谷胱甘肽和三磷酸腺苷耗竭的预防作用

Prevention by alpha-tocopherol and rutin of glutathione and ATP depletion induced by oxidized LDL in cultured endothelial cells.

作者信息

Schmitt A, Salvayre R, Delchambre J, Nègre-Salvayre A

机构信息

Department of Biochemistry-Metabolic Disease Laboratory, University Paul Sabatier, Toulouse, France.

出版信息

Br J Pharmacol. 1995 Oct;116(3):1985-90. doi: 10.1111/j.1476-5381.1995.tb16402.x.

DOI:10.1111/j.1476-5381.1995.tb16402.x

PMID:8640336

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1908932/

Abstract

Oxidized low density lipoproteins (LDL) are thought to play an important role in atherogenesis. Mildly oxidized LDL are cytotoxic to cultured endothelial cells. Toxic doses of oxidized LDL promote the peroxidation of cellular lipids (beginning at 6 h and being maximal after 12 h of pulse with oxidized LDL) and glutathione and ATP depletion (beginning after 15 h of pulse and evolving concurrently with the cytotoxicity). 2. Antioxidants from 3 different classes (rutin, ascorbic acid and alpha-tocopherol) were compared as to their ability to inhibit the cytotoxic effect of oxidized LDL to endothelial cells. 3. Effective concentrations of alpha-tocopherol inhibited cellular lipid peroxidation, glutathione and ATP depletion and the cytotoxic effect. 4. Ascorbic acid was less effective than alpha-tocopherol and rutin, and exhibited a dose-dependent biphasic effect in the presence of oxidized LDL. 5. Effective concentrations of rutin inhibited glutathione and ATP depletion as well as cytotoxicity, but did not block cellular lipid peroxidation. This suggests that the glutathione and ATP depletion is directly correlated to the cytotoxicity of oxidized LDL, whereas cellular lipid peroxidation is probably not directly the cause of cellular damage leading to cell death. 6. The association of antioxidants of 3 different classes allowed the suppression of the biphasic effect of ascorbic acid and increased the efficacy of the protective effect. The potential consequences for prevention of the pathogenic role of oxidized LDL in endothelial injury are discussed.

摘要

氧化型低密度脂蛋白（LDL）被认为在动脉粥样硬化形成过程中起重要作用。轻度氧化的LDL对培养的内皮细胞具有细胞毒性。氧化型LDL的毒性剂量会促进细胞脂质的过氧化（在与氧化型LDL脉冲处理6小时后开始，12小时后达到最大值）以及谷胱甘肽和三磷酸腺苷（ATP）的消耗（在脉冲处理15小时后开始，并与细胞毒性同时发展）。2. 比较了来自3个不同类别的抗氧化剂（芦丁、抗坏血酸和α-生育酚）抑制氧化型LDL对内皮细胞细胞毒性作用的能力。3. α-生育酚的有效浓度可抑制细胞脂质过氧化、谷胱甘肽和ATP的消耗以及细胞毒性作用。4. 抗坏血酸的效果不如α-生育酚和芦丁，并且在存在氧化型LDL的情况下表现出剂量依赖性双相效应。5. 芦丁的有效浓度可抑制谷胱甘肽和ATP的消耗以及细胞毒性，但不能阻止细胞脂质过氧化。这表明谷胱甘肽和ATP的消耗与氧化型LDL的细胞毒性直接相关，而细胞脂质过氧化可能不是导致细胞损伤和细胞死亡的直接原因。6. 3个不同类别的抗氧化剂联合使用可抑制抗坏血酸的双相效应并增强保护作用的效果。文中讨论了预防氧化型LDL在内皮损伤中的致病作用的潜在后果。