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大鼠和人类静脉注射乳糜微粒样脂质乳剂后血浆中甘油三酯和胆固醇酯的清除情况。

Clearance from plasma of triacylglycerol and cholesteryl ester after intravenous injection of chylomicron-like lipid emulsions in rats and man.

作者信息

Redgrave T G, Ly H L, Quintao E C, Ramberg C F, Boston R C

机构信息

Department of Physiology, University of Western Australia, Nedlands.

出版信息

Biochem J. 1993 Mar 15;290 ( Pt 3)(Pt 3):843-7. doi: 10.1042/bj2900843.

Abstract

Chylomicrons transport fat and cholesterol via lymphatic vessels from the intestine into the bloodstream. The understanding of the metabolism of chylomicrons in man has been slowed by the difficulty of obtaining lymph chylomicrons for experimental studies. Acceptable methods for the study of chylomicron clearance in man are required, because the metabolism of chylomicrons may be abnormal in diseases such as diabetes mellitus. Metabolism of chylomicrons may also play a role in the development of atherosclerosis. In the present work, lipid emulsions were used as a physical model of chylomicrons. Triacylglycerol-rich lipid emulsions labelled with tracer amounts of radioactive triolein and cholesteryl oleate were prepared by sonication and purified by density gradient ultracentrifugation, then injected into unanaesthetized rats and normal human subjects. Plasma radioactivities were measured for 30 min in rats and 90 min in human subjects. Rat lymph chylomicrons were also injected into rats for comparison with the clearance of the lipid emulsions. The plasma clearance data for triacylglycerols and cholesteryl esters were fitted with a kinetic model using the SAAM/CONSAM programs. Multiple studies analysis of the individual studies in each group was used to obtain estimates of the parameter average values and variabilities. The plasma residence times of the lipid labels were obtained from the fitted clearance data. Our results suggest that information about chylomicron metabolism in man can be obtained by analysis of the plasma clearance data following the injection of suitably labelled chylomicron-like lipid emulsions. Our data provide a baseline for comparisons with individuals having abnormalities of lipid metabolism or risk factors for arteriosclerosis.

摘要

乳糜微粒通过淋巴管将脂肪和胆固醇从肠道运输到血液中。由于难以获取用于实验研究的淋巴乳糜微粒,对人体中乳糜微粒代谢的了解进展缓慢。由于在糖尿病等疾病中乳糜微粒的代谢可能异常,因此需要有可接受的方法来研究人体中乳糜微粒的清除情况。乳糜微粒的代谢在动脉粥样硬化的发展中也可能起作用。在本研究中,脂质乳剂被用作乳糜微粒的物理模型。通过超声处理制备了用微量放射性三油精和胆固醇油酸酯标记的富含三酰甘油的脂质乳剂,并通过密度梯度超速离心进行纯化,然后注射到未麻醉的大鼠和正常人体受试者体内。在大鼠中测量血浆放射性30分钟,在人体受试者中测量90分钟。还将大鼠淋巴乳糜微粒注射到大鼠体内,以与脂质乳剂的清除情况进行比较。使用SAAM/CONSAM程序,将三酰甘油和胆固醇酯的血浆清除数据与动力学模型进行拟合。对每组中的个体研究进行多项研究分析,以获得参数平均值和变异性的估计值。脂质标记物的血浆停留时间从拟合的清除数据中获得。我们的结果表明,通过分析注射适当标记的类乳糜微粒脂质乳剂后的血浆清除数据,可以获得有关人体中乳糜微粒代谢的信息。我们的数据为与脂质代谢异常或有动脉硬化风险因素的个体进行比较提供了基线。

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