Liu G Q, Bengtsson-Olivecrona G, Ostergaard P, Olivecrona T
Department of Medical Biochemistry and Biophysics, University of Umeå, Sweden.
Biochem J. 1991 Feb 1;273 ( Pt 3)(Pt 3):747-52. doi: 10.1042/bj2730747.
This study compares a low-Mr heparin preparation with conventional heparin with respect to its interaction with lipoprotein lipase (LPL) in vitro and its effects on the enzyme in vivo. Both heparin preparations were polydisperse in binding to LPL, but on average the low-Mr preparation showed lower affinity. Thus both conventional and low-Mr heparin bound quantitatively to immobilized LPL, and were eluted as broad peaks when a salt gradient was applied, but the peak for low-Mr heparin was shifted towards lower salt concentrations. To displace LPL from immobilized heparin a higher concentration of low-Mr than of conventional heparin was needed. Injection of the low-Mr heparin into intact rats resulted in lower plasma LPL activity than did injection of an equal mass of conventional heparin, but when the liver was excluded from the circulation both heparin preparations resulted in similar plasma LPL activities. In perfused rat hearts, low-Mr heparin had at least the same effect on the release of LPL activity as did conventional heparin. In perfused livers, on the other hand, low-Mr heparin was less effective than conventional heparin in preventing the rapid uptake of exogenous labelled LPL. Hence the apparently lower average affinity of low-Mr heparin for LPL does not result in a demonstrably lower potency to release the enzyme from endothelial binding sites in peripheral tissues, but does result in a substantially decreased effect on the hepatic clearance of the enzyme.
本研究比较了一种低分子量肝素制剂与传统肝素在体外与脂蛋白脂肪酶（LPL）的相互作用以及在体内对该酶的影响。两种肝素制剂在与LPL结合时均为多分散性，但平均而言，低分子量制剂显示出较低的亲和力。因此，传统肝素和低分子量肝素均能定量结合至固定化的LPL，当应用盐梯度时，它们均以宽峰形式被洗脱，但低分子量肝素的峰向较低盐浓度方向移动。为了从固定化肝素上置换LPL，需要比传统肝素更高浓度的低分子量肝素。向完整大鼠注射低分子量肝素导致的血浆LPL活性低于注射等量传统肝素，但当肝脏被排除在循环之外时，两种肝素制剂导致的血浆LPL活性相似。在灌注的大鼠心脏中，低分子量肝素对LPL活性释放的影响至少与传统肝素相同。另一方面，在灌注的肝脏中，低分子量肝素在阻止外源性标记LPL的快速摄取方面比传统肝素效果差。因此，低分子量肝素对LPL的平均亲和力明显较低，这并未导致其从外周组织内皮结合位点释放该酶的效力明显降低，但确实导致其对该酶肝脏清除的影响大幅降低。
