Korutla L N, Stewart G J, Lasz E C, Maione T E, Niewiarowski S
Department of Physiology, Temple University School of Medicine, Philadelphia, PA 19140.
Thromb Haemost. 1994 May;71(5):609-14.
Recombinant platelet factor 4 (rPF4) efficiently neutralized heparin anticoagulant activity in rats without the adverse effect of protamine sulfate (PS) (Circulation 1992; 85: 1102). This study confirmed that rPF4 and PS neutralized heparin in rats. In vitro addition of excess PS but not rPF4 to plasma prolonged the activated partial thromboplastin time. Injection of rPF4 or PS 2 min following injection of 3H-heparin augmented loss of radioactivity from the circulation over the first 2 min but did not affect the half life of 3H-heparin for the next 58 min. PS was coupled to 4-(p-Azidosalicylamido)butylamine (ASBA), radioiodinated and purified by means of heparin-agarose chromatography. Heparin prevented the rapid loss of 125I-rPF4 from the circulation within the first 2 min but modestly increased loss of radioiodinated derivatized PS. Heparin extended the half-life of derivatized radioiodinated PS (measured between 2 and 60 min after injection) while modestly shortening that of 125I-rPF4. Both radioiodinated heparin binding proteins accumulated predominantly in liver and kidney. A greater percentage of radioactivity was found in these organs with rPF4 than with PS but more PS was found in urine. A larger percentage of radioiodinated derivatized PS than 125I-rPF4 was undetected. These results indicate that rPF4 and PS affect the kinetics of heparin clearance similarly but that organ deposition of the two agents may differ and offer an explanation of different physiological effects seen previously.
重组血小板因子4（rPF4）可有效中和大鼠体内的肝素抗凝活性，且无硫酸鱼精蛋白（PS）的不良反应（《循环》1992年；85：1102）。本研究证实rPF4和PS可在大鼠体内中和肝素。体外向血浆中添加过量的PS而非rPF4可延长活化部分凝血活酶时间。注射3H-肝素后2分钟注射rPF4或PS，在前2分钟内增强了循环中放射性的损失，但在接下来的58分钟内未影响3H-肝素的半衰期。PS与4-（对-叠氮水杨酰胺基）丁胺（ASBA）偶联，进行放射性碘化并通过肝素-琼脂糖色谱法纯化。肝素可防止125I-rPF4在最初2分钟内从循环中快速流失，但适度增加了放射性碘化衍生化PS的流失。肝素延长了衍生化放射性碘化PS的半衰期（注射后2至60分钟测量），同时适度缩短了125I-rPF4的半衰期。两种放射性碘化肝素结合蛋白主要在肝脏和肾脏中蓄积。与PS相比，rPF4在这些器官中发现的放射性百分比更高，但在尿液中发现的PS更多。未检测到的放射性碘化衍生化PS的百分比高于125I-rPF4。这些结果表明，rPF4和PS对肝素清除动力学的影响相似，但两种药物在器官中的沉积可能不同，并为先前观察到的不同生理效应提供了解释。
