Lefevre M, Keen C L, Lönnerdal B, Hurley L S, Schneeman B O
J Nutr. 1986 Sep;116(9):1735-46. doi: 10.1093/jn/116.9.1735.
Male Sprague-Dawley rats (10 per group) were fed diets adequate (control) or deficient (CuDef) in copper for 6 wk. In the CuDef group, plasma total cholesterol, high density lipoprotein (HDL) cholesterol and apoA-I levels were significantly higher than in controls. Apolipoprotein analysis of the HDL fractions revealed a relative enrichment of apoE in the CuDef group. Size analysis of 1.21 density lipoproteins by nondenaturing gradient gel electrophoresis demonstrated the presence of more material migrating in the size range of HDL1 in the CuDef group. Separation of HDL into apoE-rich and apoA-I-rich fractions by heparin-affinity chromatography confirmed the presence of increased apoE-rich HDL in the CuDef group. To determine the mechanism responsible for higher apoE-rich HDL in the CuDef group, the lipoprotein receptor binding activity in hepatic membranes from the control and CuDef group was assayed. Kinetic analysis of the binding data revealed that the lipoprotein binding assay was primarily measuring the activity of the HDL receptor, which is not apoE mediated. When corrected for differential enrichment of plasma membrane, hepatic membranes from the CuDef group bound significantly fewer lipoproteins than did controls. Furthermore, the hepatic receptor binding activity was negatively correlated with the proportion of HDL enriched with apoE.
将雄性Sprague-Dawley大鼠（每组10只）分别用含适量铜（对照）或低铜（铜缺乏）的饲料喂养6周。在铜缺乏组中，血浆总胆固醇、高密度脂蛋白（HDL）胆固醇和载脂蛋白A-I水平显著高于对照组。对HDL组分进行载脂蛋白分析发现，铜缺乏组中载脂蛋白E相对富集。通过非变性梯度凝胶电泳对1.21密度脂蛋白进行大小分析表明，铜缺乏组中在HDL1大小范围内迁移的物质更多。通过肝素亲和色谱将HDL分离为富含载脂蛋白E和富含载脂蛋白A-I的组分，证实铜缺乏组中富含载脂蛋白E的HDL增加。为了确定铜缺乏组中富含载脂蛋白E的HDL水平升高的机制，对对照组和铜缺乏组肝细胞膜中的脂蛋白受体结合活性进行了测定。对结合数据的动力学分析表明，脂蛋白结合试验主要测量的是HDL受体的活性，而不是由载脂蛋白E介导的。校正质膜的差异富集后，铜缺乏组肝细胞膜结合的脂蛋白明显少于对照组。此外，肝受体结合活性与富含载脂蛋白E的HDL比例呈负相关。
