Fantappiè S, Crestani M, Bosisio E, Galli G, Maggi F M, Corsini A, Catapano A L
Institute of Pharmacological Sciences, School of Pharmacy, University of Milan, Italy.
Atherosclerosis. 1989 Apr;76(2-3):163-71. doi: 10.1016/0021-9150(89)90100-7.
The aim of this study was to characterize the plasma lipoprotein pattern and some aspects of cholesterol metabolism in a line of hyperlipemic male rats. Plasma cholesterol and triglycerides were increased about 3-fold as compared to control animals (238 vs. 75 and 185 vs. 59 mg/dl respectively). The plasma lipoprotein distribution and the chemical composition of the isolated lipoproteins was unaffected. Plasma triglyceride production rate was increased (40%, P less than 0.01) and post-heparin lipoprotein lipase activity in plasma decreased (-28%, P less than 0.01) in the hyperlipemic rat. The activity of 3 enzymes involved in cholesterol metabolism (HMG-CoA reductase, cholesterol 7 alpha-hydroxylase, and acyl-CoA cholesterol-acyltransferase) did not differ from control values. 3H2O incorporation into digitonin-precipitable sterols, however, was significantly higher than in controls. This finding was due, in part, to an increased liver weight in the hyperlipemic animals. Furthermore kinetic data using 125I-LDL showed that the fractional catabolic rate of lipoprotein was within the normal range, while the synthetic rate of LDL protein was increased (0.67 vs. 0.3 mg/kg/h, P less than 0.01) in the hyperlipemic rat. These observations suggest that multiple metabolic defects underline the hyperlipemia observed in this animal model.
本研究的目的是对一组高脂血症雄性大鼠的血浆脂蛋白模式及胆固醇代谢的某些方面进行特征描述。与对照动物相比，血浆胆固醇和甘油三酯增加了约3倍（分别为238 vs. 75以及185 vs. 59 mg/dl）。血浆脂蛋白分布及分离出的脂蛋白的化学组成未受影响。高脂血症大鼠的血浆甘油三酯生成率增加（40%，P<0.01），血浆中肝素后脂蛋白脂肪酶活性降低（-28%，P<0.01）。参与胆固醇代谢的3种酶（HMG-CoA还原酶、胆固醇7α-羟化酶和酰基辅酶A胆固醇酰基转移酶）的活性与对照值无差异。然而，3H2O掺入洋地黄皂苷可沉淀固醇中的量显著高于对照组。这一发现部分归因于高脂血症动物肝脏重量增加。此外，使用125I-LDL的动力学数据表明，脂蛋白的分解代谢率在正常范围内，而高脂血症大鼠中LDL蛋白的合成率增加（0.67 vs. 0.3 mg/kg/h，P<0.01）。这些观察结果表明，多种代谢缺陷是该动物模型中观察到的高脂血症的潜在原因。
