Jialal I, Grundy S M
Department of Clinical Nutrition, University of Texas Southwestern Medical Center, Dallas 75235.
J Clin Invest. 1991 Feb;87(2):597-601. doi: 10.1172/JCI115035.
Several lines of evidence indicate that the oxidative modification of low density lipoproteins (LDL) may provide an important link between plasma LDL and the genesis of the atherosclerotic lesion. Ascorbate is an important water-soluble, chain-breaking antioxidant in humans. Probucol, a lipid-soluble antioxidant drug has been shown to retard the progression of atherosclerosis. The aim of the present study was to compare the effects of probucol and physiologic levels of ascorbate on the oxidative modification of LDL in both a cell-free (2.5 microM Cu++ in phosphate-buffered saline) and cellular system (human monocyte macrophages in Ham's F-10 medium). Both ascorbate and probucol inhibited the oxidative modification of LDL in both systems to a similar degree as evidenced by the thiobarbituric acid-reacting substance activity, electrophoretic mobility, and degradation by macrophages. However, whereas co-incubation with physiologic levels of ascorbate resulted in a substantial preservation of the alpha-tocopherol, gamma-tocopherol, and beta-carotene of the LDL, probucol in concentrations ranging from 10 to 80 microM failed to protect these antioxidants. Thus, in addition to being as potent as probucol in inhibiting the oxidation of LDL, ascorbate in contrast preserves the endogenous antioxidants in the LDL.
多项证据表明，低密度脂蛋白（LDL）的氧化修饰可能在血浆LDL与动脉粥样硬化病变的发生之间提供重要联系。抗坏血酸是人体内一种重要的水溶性断链抗氧化剂。普罗布考是一种脂溶性抗氧化药物，已被证明可延缓动脉粥样硬化的进展。本研究的目的是比较普罗布考和生理水平的抗坏血酸在无细胞体系（磷酸盐缓冲盐水中含2.5 microM Cu++）和细胞体系（Ham's F-10培养基中的人单核巨噬细胞）中对LDL氧化修饰的影响。抗坏血酸和普罗布考在两个体系中均以相似程度抑制LDL的氧化修饰，这可通过硫代巴比妥酸反应物质活性、电泳迁移率以及巨噬细胞降解来证明。然而，与生理水平的抗坏血酸共同孵育会导致LDL中的α-生育酚、γ-生育酚和β-胡萝卜素大量保留，而浓度范围为10至80 microM的普罗布考未能保护这些抗氧化剂。因此，抗坏血酸除了在抑制LDL氧化方面与普罗布考一样有效外，还能保留LDL中的内源性抗氧化剂。
