METABOLIC BEHAVIOR IN RATS OF A NONPROTEIN MICROEMULSION RESEMBLING LOW-DENSITY-LIPOPROTEIN
METABOLIC BEHAVIOR IN RATS OF A NONPROTEIN MICROEMULSION RESEMBLING LOW-DENSITY-LIPOPROTEIN
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DOI：
10.1007/bf02535988
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发表时间：
1993-08-01
期刊：
影响因子：
1.9
通讯作者：
MESQUITA, CH
中科院分区：
文献类型：
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作者：
MARANHAO, RC;CESAR, TB;MESQUITA, CH
无蛋白微乳(LDE)的脂组成与低密度脂蛋白(LDL)相似，用于大鼠的代谢研究，以比较LDE与天然脂蛋白。将放射性脂质标记的LDE注入雄性Wistar大鼠的血流中，并在注射后12h内定期采集血浆标本，观察标记脂质的血浆动力学。动物处死后切除的组织样本中，也测量了不同组织对24小时LDE的摄取。我们发现低密度脂蛋白的血浆动力学与天然低密度脂蛋白相似[胆固醇酯的分数清除率(FCR)，0.42+/-0.11h-1]。LDE摄取的主要部位是肝脏，LDE注射的放射性的组织分布与人们预期的低密度脂蛋白一样。为了测试低密度脂蛋白是否被特定的低密度脂蛋白受体摄取，将低密度脂蛋白乳剂注射到用17α-乙炔雌二醇处理的大鼠体内，已知可以增加这些受体的活性；正如预期的那样，低密度脂蛋白从血流中的清除增加(FCR=0.90+/-0.35h-1)。另一方面，通过预先注入大量淋巴乳糜粒清除残留物的受体的饱和并没有改变LDE的血浆动力学。这些结果表明，LDE被B、E受体清除，而不是通过E受体清除残留物。在低密度脂蛋白中加入游离胆固醇可增加低密度脂蛋白的血浆清除量。培养研究还表明，低密度脂蛋白结合了多种载脂蛋白，包括载脂蛋白E，一种通过特定受体识别脂蛋白的配体。我们的数据表明，低密度脂蛋白可作为检测低密度脂蛋白代谢和B、E受体功能的有用工具。
A protein-free microemulsion (LDE) with a lipid composition resembling that of low-density lipoprotein (LDL) was used in metabolic studies in rats to compare LDE with the native lipoprotein. LDE labeled with radioactive lipids was injected into the bloodstream of male Wistar rats, and plasma kinetics of the labeled lipids were followed on plasma samples collected at regular intervals for 12 h after injection. The 24-h LDE uptake by different tissues was also measured in tissue samples excised after the animals had been sacrificed. We found that LDE plasma kinetics were similar to those described for native LDL [fractional clearance rate (FCR) of cholesteryl ester, 0.42 +/- 0.11 h-1]. The major site for LDE uptake was the liver, and the tissue distribution of the LDE injected radioactivity was as one would expect for LDL. To test whether LDE was taken up by the specific LDL receptors, the LDE emulsion was injected into rats treated with 17alpha-ethinylestradiol, which is known to increase the activity of these receptors; as expected, removal of LDE from the bloodstream increased (FCR = 0.90 +/- 0.35 h-1). On the other hand, saturation of the receptors that remove remnants by prior infusion of massive amounts of lymph chylomicrons did not change LDE plasma kinetics. These results indicate that LDE is cleared from plasma by B,E receptors and not by the E receptors that remove remnants. Incorporation of free cholesterol into LDE increased LDE plasma clearance. Incubation studies also showed that LDE incorporates a variety of apolipoproteins, including apo E, a ligand for recognition of lipoproteins by specific receptors. Our data suggest that LDE can be a useful tool to test LDL metabolism and B,E receptor function.