Lewis G F, Lamarche B, Uffelman K D, Heatherington A C, Honig M A, Szeto L W, Barrett P H
Department of Medicine, University of Toronto, Ontario, Canada.
J Lipid Res. 1997 Sep;38(9):1771-8.
Triglyceride (TG) enrichment of high density lipoproteins (HDL) in hypertriglyceridemic states renders the particles vulnerable to lipolysis, which reduces their size. In the present study we modified the size and composition of HDL in vivo in hypertriglyceridemic humans by administering a bolus of intravenous heparin, and tested the subsequent clearance of the isolated HDL particles in rabbits and rats. HDL was isolated by ultracentrifugation from 21 moderately hypertriglyceridemic humans, 5 h after ingestion of a high fat meal and then 15 min after an intravenous heparin bolus (60 U/kg). Postprandial large TG-rich preheparin HDL and small, TG-poor postheparin HDL were labeled with either 125I or 131I. The clearance of apoA-I associated with each HDL tracer was determined by injecting the tracers 1) simultaneously (n = 13) and 2) sequentially (n = 8) into male New Zealand White rabbits, an hepatic lipase-deficient animal, and 3) by injecting the tracers simultaneously into male Sprague-Dawley rats (n = 8), an animal that has hepatic lipase. Die-away curves of each radiolabeled tracer were analyzed using a two-pool model that assumes the existence of an intravascular pool in dynamic equilibrium with an extravascular pool. In the rabbit studies, the fractional catabolic rate (FCR) of small, postheparin TG-poor HDL was greater than the FCR of the larger TG-rich HDL (11% greater in the simultaneous study, P < 0.001, and 45% greater in the sequential study, P < 0.001). Opposite results were observed in rats as large TG-rich preheparin particles showed a greater FCR (1.8-fold) than smaller TG-poor postheparin HDL (P < 0.05). These data suggest that although size and composition of HDL can influence its catabolism, the effect is not always in the same direction and depends on other factors present in vivo.
在高甘油三酯血症状态下，高密度脂蛋白（HDL）中的甘油三酯（TG）富集使这些颗粒易受脂解作用影响，从而减小其大小。在本研究中，我们通过静脉推注肝素，在体内改变了高甘油三酯血症患者体内HDL的大小和组成，并测试了随后从兔和大鼠体内分离出的HDL颗粒的清除情况。在摄入高脂肪餐后5小时，然后静脉推注肝素（60 U/kg）15分钟后，通过超速离心从21名中度高甘油三酯血症患者中分离出HDL。餐后富含大量TG的肝素前HDL和小的、TG含量低的肝素后HDL用125I或131I进行标记。通过将标记物：1）同时（n = 13）和2）依次（n = 8）注射到雄性新西兰白兔（一种肝脂酶缺陷动物）体内，以及3）同时注射到雄性Sprague-Dawley大鼠（n = 8，一种具有肝脂酶的动物）体内，来测定与每种HDL标记物相关的载脂蛋白A-I的清除情况。使用双池模型分析每个放射性标记物的衰减曲线，该模型假设存在一个与血管外池处于动态平衡的血管内池。在兔的研究中，小的、肝素后TG含量低的HDL的分解代谢率（FCR）大于较大的富含TG的HDL的FCR（同时研究中高11%，P < 0.001；顺序研究中高45%，P < 0.001）。在大鼠中观察到相反的结果，因为大的富含TG的肝素前颗粒的FCR比小的、TG含量低的肝素后HDL高（1.8倍）（P < 0.05）。这些数据表明，尽管HDL的大小和组成可影响其分解代谢，但这种影响并不总是同一方向，且取决于体内存在的其他因素。
