Harauchi T, Takano K, Matsuura M, Yoshizaki T
Jpn J Pharmacol. 1986 Apr;40(4):491-9. doi: 10.1254/jjp.40.491.
Descarboxyprothrombin (PIVKA II) is a precursor of prothrombin without biological activity, and it increases with vitamin K deficiency. We studied the time course changes in liver and plasma levels of PIVKA II during the progress of vitamin K deficiency in rats. Good correlation was observed between liver PIVKA II and plasma PIVKA II and between liver or plasma PIVKA II and plasma prothrombin in experiments in which rats were fed a vitamin K-deficient diet. Feeding of a vitamin K-deficient diet or fasting caused marked increases in liver and plasma PIVKA II in male rats and a weaker response in female rats. Warfarin, a vitamin K antagonist, caused an abrupt increase in liver PIVKA II, but the increase in plasma PIVKA II was delayed about 3 hr. Plasma prothrombin decreased from about 30 min later. Factor VII decreased similarly to prothrombin, and changes in the prothrombin time and activated partial thromboplastin time were slower than the changes in these substances. Sex differences were not seen in these warfarin actions. These observations indicate that liver and plasma PIVKA II are sensitive markers of vitamin K deficiency in rats, and assay of PIVKA II can be useful for analyzing the action mechanism of drugs which influence blood coagulation.
脱羧基凝血酶原（异常凝血酶原II）是一种无生物活性的凝血酶原前体，其水平会随着维生素K缺乏而升高。我们研究了大鼠维生素K缺乏过程中肝脏和血浆中异常凝血酶原II水平随时间的变化。在给大鼠喂食维生素K缺乏饮食的实验中，观察到肝脏异常凝血酶原II与血浆异常凝血酶原II之间、肝脏或血浆异常凝血酶原II与血浆凝血酶原之间存在良好的相关性。喂食维生素K缺乏饮食或禁食会导致雄性大鼠肝脏和血浆中异常凝血酶原II显著升高，而雌性大鼠的反应较弱。维生素K拮抗剂华法林会导致肝脏异常凝血酶原II突然升高，但血浆异常凝血酶原II的升高延迟约3小时。血浆凝血酶原约30分钟后开始下降。因子VII的下降与凝血酶原相似，凝血酶原时间和活化部分凝血活酶时间的变化比这些物质的变化要慢。在这些华法林作用中未观察到性别差异。这些观察结果表明，肝脏和血浆中的异常凝血酶原II是大鼠维生素K缺乏的敏感标志物，检测异常凝血酶原II有助于分析影响血液凝固的药物的作用机制。
