Akiyama Y, Hara K, Matsumoto A, Takahashi S, Tajima T
Department of Drug Research II, Eisai Co. Ltd., Tokyo, Japan.
Biochem Pharmacol. 1995 Jun 16;49(12):1801-7. doi: 10.1016/0006-2952(94)00531-p.
To examine the physiological activities of vitamin K2 (menaquinone, MK) homologues with different numbers of isoprene units, MK with 1-14 isoprene units and menadione (MK-0) were administered to rats with hypoprothrombinaemia, and the absorption, concentration in liver and ameliorating effect of these MK on hypoprothrombinaemia were compared. Hypoprothrombinaemia was induced by giving a vitamin K-deficient diet and warfarin (0.06 mg/kg body weight) for 8 days. Before MK treatment, the MK were undetectable in plasma and liver. At 6 hr after oral MK administration (0.1 mg/kg): MK was not detected in the plasma in rats treated with MK with 1, 2, 3 or more than 12 isoprene units; the MK level in the liver was increased but blood coagulation activity was not improved in rats treated with MK with 0, 9, 10 or 11 isoprene units; the MK level in the liver was increased and hypoprothrombinaemia was slightly improved in rats treated with MK with 7 or 8 isoprene units; and the MK level in the liver was increased and hypoprothrombinaemia was markedly improved in rats treated with MK with 4, 5 or 6 isoprene units. Almost identical results were observed 3 hr after intravenous injection of MK with 4, 5 or 6 isoprene units (10 nmol/kg). These findings suggest that the number of isoprene units of MK is an important factor in its absorption and incorporation into the liver and that the ameliorating effect of MK on hypoprothrombinaemia does not parallel their concentrations in the liver.
为研究具有不同异戊二烯单元数的维生素K2（甲萘醌，MK）同系物的生理活性，将含有1 - 14个异戊二烯单元的MK及甲萘醌（MK - 0）给予患有低凝血酶原血症的大鼠，并比较这些MK的吸收情况、在肝脏中的浓度及其对低凝血酶原血症的改善作用。通过给予维生素K缺乏饮食和华法林（0.06 mg/kg体重）8天来诱导低凝血酶原血症。在MK治疗前，血浆和肝脏中未检测到MK。口服MK（0.1 mg/kg）后6小时：给予含有1、2、3或超过12个异戊二烯单元的MK的大鼠血浆中未检测到MK；给予含有0、9、10或11个异戊二烯单元的MK的大鼠肝脏中MK水平升高，但凝血活性未改善；给予含有7或8个异戊二烯单元的MK的大鼠肝脏中MK水平升高，低凝血酶原血症略有改善；给予含有4、5或6个异戊二烯单元的MK的大鼠肝脏中MK水平升高，低凝血酶原血症明显改善。静脉注射含有4、5或6个异戊二烯单元的MK（10 nmol/kg）3小时后观察到几乎相同的结果。这些发现表明，MK的异戊二烯单元数是其吸收和进入肝脏的一个重要因素，并且MK对低凝血酶原血症的改善作用与其在肝脏中的浓度并不平行。
