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兔体内高密度脂蛋白胆固醇酯细胞摄取途径的评估

Evaluation of pathways for the cellular uptake of high density lipoprotein cholesterol esters in rabbits.

作者信息

Goldberg D I, Beltz W F, Pittman R C

机构信息

Department of Medicine, University of California, San Diego, La Jolla 92093.

出版信息

J Clin Invest. 1991 Jan;87(1):331-46. doi: 10.1172/JCI114991.

DOI:10.1172/JCI114991
PMID:1985105
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC295057/
Abstract

Cholesterol esters (CE) formed in HDL by lecithin:cholesterol acyltransferase are thought to mediate the return of cholesterol from extrahepatic tissues to the liver for excretion or reutilization. Several pathways may be involved in that process. Tracer kinetics were used to estimate the contributions of the various pathways to cellular uptake of HDL CE in rabbits. Tracers of HDL CE, HDL apo A-I, LDL apo B, and VLDL CE were simultaneously injected intravenously. Plasma decays were followed for 24 h in 4 lipoprotein pools: HDL without apo E, HDL with apo E, LDL, and VLDL. Kinetic analysis of the resulting plasma decay curves revealed that the preponderance of plasma CE (greater than 90%) originated in the HDL fraction. About 70% of HDL CE were cleared from plasma after transfer to LDL and VLDL, 20% were cleared directly from the HDL pool without HDL particle uptake ("selective" uptake), and 10% were cleared in HDL particles (including particles containing apo E). Since rabbits have about four times the plasma cholesterol ester transfer activity of man, and since the transfer pathway must compete with the selective uptake pathway, these results make it likely that selective uptake plays a substantial role in humans in the clearance of HDL CE.

摘要

卵磷脂胆固醇酰基转移酶在高密度脂蛋白(HDL)中形成的胆固醇酯(CE)被认为介导胆固醇从肝外组织返回肝脏进行排泄或再利用。该过程可能涉及多种途径。示踪动力学被用于估计家兔中各种途径对HDL CE细胞摄取的贡献。同时静脉注射HDL CE、HDL载脂蛋白A-I、低密度脂蛋白(LDL)载脂蛋白B和极低密度脂蛋白(VLDL)CE的示踪剂。在4个脂蛋白池(不含载脂蛋白E的HDL、含载脂蛋白E的HDL、LDL和VLDL)中追踪血浆衰变24小时。对所得血浆衰变曲线的动力学分析表明,血浆CE的主要部分(超过90%)起源于HDL部分。约70%的HDL CE在转移至LDL和VLDL后从血浆中清除,20%在未摄取HDL颗粒的情况下直接从HDL池中清除(“选择性”摄取),10%在HDL颗粒(包括含载脂蛋白E的颗粒)中清除。由于家兔的血浆胆固醇酯转移活性约为人的四倍,且转移途径必须与选择性摄取途径竞争,因此这些结果表明选择性摄取在人类清除HDL CE过程中可能起重要作用。

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本文引用的文献

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Differences in plasma cholesteryl ester transfer activity in sixteen vertebrate species.16种脊椎动物血浆胆固醇酯转移活性的差异
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Use of radiolabeled hexadecyl cholesteryl ether as a liposome marker.使用放射性标记的十六烷基胆固醇醚作为脂质体标记物。
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Concentration and composition of lipoproteins in blood plasma of the WHHL rabbit. An animal model of human familial hypercholesterolemia.WHHL兔血浆中脂蛋白的浓度和组成。人类家族性高胆固醇血症的动物模型。
Arteriosclerosis. 1982 Nov-Dec;2(6):467-74. doi: 10.1161/01.atv.2.6.467.
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Delayed clearance of very low density and intermediate density lipoproteins with enhanced conversion to low density lipoprotein in WHHL rabbits.在WHHL兔中,极低密度脂蛋白和中间密度脂蛋白清除延迟,向低密度脂蛋白的转化增强。
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