Asakura H, Aoshima K, Suga Y, Yamazaki M, Morishita E, Saito M, Miyamoto K, Nakao S
Department of Internal Medicine (III), Kanazawa University School of Medicine, Ishikawa, Japan.
Thromb Haemost. 2001 Feb;85(2):287-90.
1Alpha,25-dihydroxyvitamin D3 (active form of vitamin D3; vitamin D3) has been reported to induce the upregulation of thrombomodulin and downregulation of tissue factor (TF) on monocytes. The possibility exists that vitamin D3 prevents the development of disseminated intravascular coagulation (DIC). In particular, monocyte TF production plays an important role in the pathophysiology of DIC in septic patients. We have attempted to determine whether vitamin D3 is effective against DIC in a rat model induced by lipopolysaccharides (LPS) (30 mg/kg, 4 h) or TF (3.75 U/kg, 4 h) using selective hemostatic parameters, markers of organ dysfunction and pathological findings (assessment of glomelular fibrin deposition). Vitamin D3 was administered orally each day at a dose of 2.0 mg/kg/day for 3 days, or low molecular weight heparin (LMWH 200 u/kg; i.v.) was given 10 min before the injection of TF or LPS in each treatment group. Vitamin D3 was effective against DIC in the rat model induced by LPS only, whereas LMWH was effective against DIC in both rat models induced by either TF or LPS. The anti-DIC effect of vitamin D3 was equal to (or more potent than) that of LMWH. The results suggested that vitamin D3 was useful for the treatment of LPS-induced DIC, and that the assessment of a drug's efficacy should be done carefully given the markedly different results obtained according to the agents used to induce DIC.
1α,25 - 二羟基维生素D3（维生素D3的活性形式；维生素D3）已被报道可诱导单核细胞上血栓调节蛋白的上调和组织因子（TF）的下调。维生素D3有可能预防弥散性血管内凝血（DIC）的发生。特别是，单核细胞TF的产生在脓毒症患者DIC的病理生理学中起重要作用。我们试图使用选择性止血参数、器官功能障碍标志物和病理结果（肾小球纤维蛋白沉积评估）来确定维生素D3对脂多糖（LPS）（30 mg/kg，4小时）或TF（3.75 U/kg，4小时）诱导的大鼠DIC模型是否有效。在每个治疗组中，维生素D3以2.0 mg/kg/天的剂量口服给药3天，或者在注射TF或LPS前10分钟给予低分子量肝素（LMWH 200 u/kg；静脉注射）。维生素D3仅对LPS诱导的大鼠DIC模型有效，而LMWH对TF或LPS诱导的两种大鼠DIC模型均有效。维生素D3的抗DIC作用等同于（或强于）LMWH。结果表明，维生素D3可用于治疗LPS诱导的DIC，并且鉴于根据用于诱导DIC的药物所获得的结果明显不同，应谨慎评估药物的疗效。
