Izutani W, Fujita M, Nishizawa K, Koga J
Development and Research Laboratories, JCR Pharmaceuticals Co., Ltd., Kobe, Japan.
Biol Pharm Bull. 2000 Sep;23(9):1046-50. doi: 10.1248/bpb.23.1046.
We compared urinary protein C inhibitor (uPCI) with low molecular weight heparin (LMWH) in terms of the effect on the pathophysiology of disseminated intravascular coagulation (DIC), such as hypercoagulation, induction of secondary fibrinolysis and organ failure, using lipopolysaccharide (LPS)-induced DIC in rats. The uPCI (0.5 and 1.0 mg/kg) administration significantly inhibited both the decrease in fibrinogen level and the increase in fibrin/fibrinogen degradation products (FDP) level, and the effects compared favorably with those of LMWH (100 and 200 IU/kg). Both uPCI (0.5 and 1.0 mg/kg) and a low dose of LMWH also inhibited the increases in the levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), thrombin, and plasma kallikrein equally, but a high dose of LMWH did not inhibit the changes in those parameters. Furthermore, uPCI dose-dependently prevented the prolongation of activated partial thromboplastin time (APTT), while LMWH excessively prolonged APTT at a high dose. These results suggest that the preventive effect of uPCI on the pathophysiology of DIC compares favorably with that of LMWH, including the lack of a hemorrhagic reaction in contrast to LMWH.
我们使用脂多糖(LPS)诱导的大鼠弥散性血管内凝血(DIC)模型,比较了尿蛋白C抑制剂(uPCI)和低分子量肝素(LMWH)对DIC病理生理学的影响,如高凝状态、继发性纤溶的诱导和器官衰竭。给予uPCI(0.5和1.0mg/kg)显著抑制了纤维蛋白原水平的降低和纤维蛋白/纤维蛋白原降解产物(FDP)水平的升高,其效果与LMWH(100和200IU/kg)相当。uPCI(0.5和1.0mg/kg)和低剂量的LMWH同样抑制了天冬氨酸转氨酶(AST)、丙氨酸转氨酶(ALT)、凝血酶和血浆激肽释放酶水平的升高,但高剂量的LMWH并未抑制这些参数的变化。此外,uPCI剂量依赖性地防止了活化部分凝血活酶时间(APTT)的延长,而LMWH在高剂量时会过度延长APTT。这些结果表明,uPCI对DIC病理生理学的预防作用与LMWH相当,与LMWH相比,其不存在出血反应。