組織因子および LPS 誘発ラット DIC モデルに対する all-trans retinoic acid, 活性化ビタミン D3, 低分子ヘリパリンの薬効比較検討  [in Japanese] Comparative Study All-trans Retinoic Acid, Active Form of Vitamin D_3 and Low Molecular Weight Heparin in Two Types of DIC in Rats Induced by Tissue Factor or Lipoplysaccharide  [in Japanese]

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Abstract

組織因子 (TF) または lipopolysaccharide (LPS) 誘発による Disseminated intravascular coagulation (DIC) モデル (それぞれTF-DIC, LPS-DICと略) に対する all-<i>trans</i> retinoic acid (ATRA), 活性化ビタミンD<sub>3</sub> (Vit D<sub>3</sub>) および低分子ヘパリン (LMWH) の薬効を比較検討した. TF-DICモデルに対し, LMWHは血小板数とフィブリノゲンの減少, D-dimer とTATの上昇を有意に抑制したが, ATRAおよび Vit D<sub>3</sub>はまったく無効であった. 一方, LPS-DICモデルに対しては, ATRA, Vit D<sub>3</sub>, LMWHともに有効であり, 腎糸球体血栓も有意に減少したが, 高用量のLMWH投与では死亡・出血が高頻度にみられた.<br>以上, 動物DICモデルを用いてDIC治療薬の薬効評価を行う際に, 両モデル間で成績が大きく異なる場合がありうることが明らかとなり, 今後の動物DICモデルを用いてのDIC研究を行う上での重要な注意点と思われた.

Tissue factor (TF) and lipopolysaccharide (LPS) were used to induce disseminated intravascular coagulation (DIC) in rats. In these TF- and LPS-induced animal DIC-models, we studied efficacy of all-<i>trans</i> retinoic acide (ATRA), vitamin D<sub>3</sub> (Vit D<sub>3</sub>) and low molecular weight heparin (LMWH) for the treatment of DIC. In the TF-DIC model, decreases in platelet counts (PLT) and plasma fibrinogen (Fbg), and increases in the D-dimer and the thrombin-antithrombin III complex (TAT) were both significantly inhibited by LMWH, but not by ATRA or Vit D<sub>3</sub>. On the other hand, all three drugs inhibited formation of fibrin thrombin significantly in the LPS-DIC model, although increase in the amount of LMWH from 200 U to 500 U resulted in higher incidence of severe bleeding and mortality. Thus care must be taken in the selection of DIC-inducing agents in animal experiments to evaluate therapeutic efficacy of these drugs that are widely accepted for the treatment of DIC in man.

Journal

  • Japanese Journal of Thrombosis and Hemostasis

    Japanese Journal of Thrombosis and Hemostasis 11(1), 65-73, 2000-02-01

    The Japanese Society on Thrombosis and Hemostasis

References:  21

Codes

  • NII Article ID (NAID)
    10008600951
  • NII NACSIS-CAT ID (NCID)
    AN10353762
  • Text Lang
    JPN
  • Article Type
    ART
  • ISSN
    09157441
  • Data Source
    CJP  J-STAGE 
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