Fatty streak formation in fat-fed mice expressing human copper-zinc superoxide dismutase
Fatty streak formation in fat-fed mice expressing human copper-zinc superoxide dismutase
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DOI：
10.1161/01.atv.17.9.1734
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发表时间：
1997-09-01
影响因子：
8.7
通讯作者：
Epstein, CJ
中科院分区：
文献类型：
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作者：
Tribble, DL;Gong, EL;Epstein, CJ
体外研究表明，铜锌超氧化物歧化酶 (CuZn-SOD) 可抑制许多可能与动脉粥样硬化形成有关的事件，包括细胞介导的 LDL 氧化。为了研究 CuZn-SOD 活性的增加是否会减少体内动脉粥样硬化的形成，我们检查了 CuZn-SOD 转基因小鼠 (n = 24) 与非转基因同窝小鼠 (n = 28) 中饮食诱导的脂肪纹形成情况。转基因动物最初是通过将含有 CuZn-SOD 基因及其调控元件的 EcoRI-BamHI 人类基因组 DNA 片段引入 B6SJL 受精卵而创建的。在目前的研究中，转基因在动脉粥样硬化易感的 C57BL/6 背景中培育了 12 代。动物从 10 周龄开始饲喂致动脉粥样硬化饮食（15% 脂肪、1.25% 胆固醇、0.5% 胆酸钠）并持续 18 周。饮食结束时，转基因动物的主动脉 SOD 活性比非转基因动物高两倍（平均值 +/- SE：46.7 +/- 5.8 对比 20.1 +/- 2.4 单位/毫克蛋白质，P
Studies in vitro have shown that copper-zinc super-oxide dismutase (CuZn-SOD) inhibits a number of events putatively involved in atherogenesis, including cell-mediated oxidation of LDL. To investigate whether increased activity of CuZn-SOD reduces atherogenesis in vivo, we examined diet-induced fatty streak formation in CuZn-SOD transgenic mice (n = 24) as compared with their nontransgenic littermates (n = 28). Transgenic animals were originally created by introduction of an EcoRI-BamHI human genomic DNA fragment containing the CuZn-SOD gene and its regulatory elements into B6SJL zygotes. For the current studies, the transgene was bred for 12 generations into the atherosclerosis-susceptible C57BL/6 background. Animals were fed atherogenic diets (15% fat, 1.25% cholesterol, 0.5% Na cholate) starting at 10 weeks of age and extending for 18 weeks. At the end of the diet period, aortic SOD activity was two-fold higher in transgenics than nontransgenics (mean +/- SE: 46.7 +/- 5.8 versus 20.1 +/- 2.4 units/mg of protein, P