Neuzil J, Christison J K, Iheanacho E, Fragonas J C, Zammit V, Hunt N H, Stocker R
Biochemistry Unit, Heart Research Institute, Camperdown, NSW, Australia.
J Lipid Res. 1998 Feb;39(2):354-68.
Exposure of plasma from apolipoprotein E gene knockout (apoE-/-) and control (CBA or C57BL/6J) mice plasma to a constant rate of aqueous peroxyl radicals (ROO.) resulted in the depletion of ascorbate, urate and alpha-tocopherol (alpha-TOH), with substantial and little lipid peroxidation, respectively. Alpha-TOH levels were 3-times higher in plasma from apoE-/- than control mice and its addition enhanced the oxidizability of control mouse plasma. In apoE-/- mouse plasma, alpha-TOH was associated primarily with very low density lipoprotein (VLDL), whereas in plasma from control mice, the vitamin was located largely in high density lipoproteins. Oxidation of isolated lipoproteins by ROO. resulted in the accumulation of lipid hydroperoxides to an extent that reflected the plasma concentration and alpha-TOH content of the different lipoprotein fractions. Oxidation of 'plasma' reconstituted from components of apoE-/- mice and/or human plasma showed that human and apoE-/- mouse lipoproteins peroxidized with similar kinetics, although the initiation of lipid peroxidation was greater in the presence of mouse than human lipoprotein-deficient plasma. Also, the chain length of lipid peroxidation in apoE-/- mouse plasma after ascorbate depletion appeared to be independent of the rate of ROO. generation. Together, these results show that the ROO. induced peroxidation of plasma lipoproteins in atherogenesis-susceptible apoE-/- mice exhibits some, though not all, features of tocopherol-mediated peroxidation (TMP). Therefore, apoE-/- mice may represent a suitable animal model to test a role for TMP in atherogenesis and the prevention of this disease by anti-TMP agents.
将载脂蛋白E基因敲除（apoE-/-）小鼠和对照（CBA或C57BL/6J）小鼠的血浆暴露于恒定速率的水性过氧自由基（ROO.）中，导致抗坏血酸、尿酸和α-生育酚（α-TOH）消耗，分别伴有大量和少量脂质过氧化。apoE-/-小鼠血浆中的α-TOH水平比对照小鼠高3倍，其添加增强了对照小鼠血浆的氧化能力。在apoE-/-小鼠血浆中，α-TOH主要与极低密度脂蛋白（VLDL）相关，而在对照小鼠血浆中，该维生素主要存在于高密度脂蛋白中。ROO.对分离的脂蛋白的氧化导致脂质氢过氧化物积累，其程度反映了不同脂蛋白组分的血浆浓度和α-TOH含量。由apoE-/-小鼠和/或人血浆成分重构的“血浆”的氧化表明，人和apoE-/-小鼠脂蛋白以相似的动力学发生过氧化，尽管在存在小鼠而非人脂蛋白缺乏血浆的情况下脂质过氧化的起始程度更大。此外，抗坏血酸消耗后apoE-/-小鼠血浆中脂质过氧化的链长似乎与ROO.的生成速率无关。总之，这些结果表明，ROO.诱导的动脉粥样硬化易感apoE-/-小鼠血浆脂蛋白过氧化表现出一些（尽管不是全部）生育酚介导的过氧化（TMP）特征。因此，apoE-/-小鼠可能是一个合适的动物模型，用于测试TMP在动脉粥样硬化中的作用以及抗TMP药物对该疾病的预防作用。
