Roach P D, Balasubramaniam S, Hirata F, Abbey M, Szanto A, Simons L A, Nestel P J
CSIRO Australia Division of Human Nutrition, Adelaide.
Biochim Biophys Acta. 1993 Oct 13;1170(2):165-72. doi: 10.1016/0005-2760(93)90067-j.
In the hamster and the rabbit, the low-density lipoprotein (LDL) receptor and cholesterol synthesis are coordinately downregulated by dietary cholesterol. In the rat, cholesterol synthesis is downregulated but LDL kinetic studies suggest that the LDL receptor is not. The aim of this study was to determine the effect of dietary cholesterol on the expression of the hepatic LDL receptor in the rat. Young (2 months) hooded and albino Wistar rats and older (9 months) Sprague-Dawley rats were used because of their reported different propensities to develop hypercholesterolaemia when fed cholesterol. Hepatic LDL receptor activity was measured using a dot blot assay with LDL-gold and LDL receptor mass was measured using an electroblot assay with a polyclonal antibody. Dietary cholesterol had no effect on the plasma cholesterol concentration in both strains of young Wistar rats but increased it in the older Sprague-Dawley rats. Cholesterol synthesis as measured with 3H2O or as indicated by 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase activity or the ratio of plasma lathosterol to cholesterol was effectively downregulated by dietary cholesterol (1% w/w) in all three strains. In contrast, dietary cholesterol increased both hepatic LDL receptor activity and mass in the young Wistar rats and had no effect on either receptor activity or mass in the older Sprague-Dawley rats. Increases in receptor activity occurred despite increases in hepatic cholesterol especially when cholic acid was added to the cholesterol diet. The effect was systemic because CL 277082, an inhibitor of intestinal cholesterol absorption, prevented the increase in LDL receptor activity.(ABSTRACT TRUNCATED AT 250 WORDS)
在仓鼠和兔子中，膳食胆固醇可协同下调低密度脂蛋白（LDL）受体及胆固醇合成。在大鼠中，胆固醇合成被下调，但LDL动力学研究表明LDL受体未受影响。本研究旨在确定膳食胆固醇对大鼠肝脏LDL受体表达的影响。选用年轻（2个月）的带帽和白化Wistar大鼠以及年长（9个月）的Sprague-Dawley大鼠，因为据报道它们在喂食胆固醇时发生高胆固醇血症的倾向不同。使用LDL-金进行斑点印迹测定法测量肝脏LDL受体活性，使用多克隆抗体通过电印迹测定法测量LDL受体质量。膳食胆固醇对两种年轻Wistar大鼠品系的血浆胆固醇浓度均无影响，但可使年长的Sprague-Dawley大鼠的血浆胆固醇浓度升高。在所有三个品系中，用3H2O测量的胆固醇合成或由3-羟基-3-甲基戊二酰辅酶A（HMG-CoA）还原酶活性或血浆羊毛甾醇与胆固醇的比率表明，膳食胆固醇（1% w/w）可有效下调胆固醇合成。相比之下，膳食胆固醇可增加年轻Wistar大鼠的肝脏LDL受体活性和质量，而对年长的Sprague-Dawley大鼠的受体活性或质量均无影响。尽管肝脏胆固醇增加，尤其是在胆固醇饮食中添加胆酸时，受体活性仍会增加。这种作用是全身性的，因为肠道胆固醇吸收抑制剂CL 277082可阻止LDL受体活性的增加。（摘要截短于250字）
