脳血栓症急性期における血管内皮細胞機能変化  エンドセリン‐1,組織プラスミノーゲンアクチベーターとそのインヒビターの変動からの解析:エンドセリン-1, 組織プラスミノーゲンアクチベーターとそのインヒビターの変動からの解析  [in Japanese] Changes in vascular endothelial cell function at the acute phase of cerebral thrombosis: Analysis from alterations in endothelin-1, tissue plasminogen activator and its inhibitor.:Analysis from alterations in endothelin-1, tissue plasminogen activator and its inhibitor  [in Japanese]

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Author(s)

    • 米波 浩二 Yonenami Kouji
    • 聖マリアンナ医科大学第二内科 Second Department of Internal Medicine, St. Marianna University School of Medicine
    • 杉原 浩 Sugihara Hiroshi
    • 聖マリアンナ医科大学第二内科 Second Department of Internal Medicine, St. Marianna University School of Medicine
    • 鴨川 旭 Kamogawa Asahi
    • 聖マリアンナ医科大学第二内科 Second Department of Internal Medicine, St. Marianna University School of Medicine

Abstract

脳血栓症急性期において, エンドセリン-1 (ET-1) は経時的に低下し, 組織プラスミノーゲンアクチベーター (t-PA) は鏡像的に増加する.今回はそのメカニズムの解析を目的に基礎的, 臨床的検討を行った.<BR>培養血管内皮細胞へのオザグレルナトリウム添加で培養液中の両因子濃度は非添加対照と差が認められない.トロンビン添加で両因子とも対照より有意の高値を示した.このことから両因子の脳血栓症急性期の変化に治療薬剤や凝固の直接的関与は否定される.急性期1~7病日のET-1とt-PAの各変化量が逆相関を示した "逆相関群" では相関しない "非相関群" に比してt-PAのインヒビターPAI-1の遊離型 (free) PAI-1の相対的高値が認められた.<BR>t-PAはET-1放出を抑制する既報の成績からt-PA増加がET-1放出を主導的に抑制し, 急性期の血栓抵抗性をfree PAI-1高値例においては誘導しているものと考えられた.すなわち, 脳血栓症治療に際しては抗血小板・抗凝固だけではなく, このt-PA・PAI-1の線溶系を考慮すべきである.

At the acute phase of cerebral thrombosis, endothelin-1 (ET-1), a vasopressor factor derived from vascula : endothelial cells, decreases with time. On the other band, tissue plasminogen activator (t-PA), a rate-determining factor of fibrinolysis, increases enantiomorphically. Elucidation of the mechanism involved is important for analyzing and for determining the guidelines for the treatment of the disease. In the present study, in an attempt to analyze the above mechanism, we conducted a basic clinical study. Release of both factors was not altered by the addition of sodium ozagrel or thrombin to cultured vascular endothelial cells. From this finding, it is denied that therapeutic drugs and coagulation may be associated with an increse in free PAI-1 which reflects the activity of PAI. In combination with previously reported results showing a decrease in the release of ET-1 following addition of t-PA, the data suggest that t-PA may influence an inhibitory effect on fibrinolysis when both factors change at the acute phase. It is considered that the increased t-PA may inhibit predominantly the relcase of ET-1 and induce resistance against thrombosis at the acute phase. In the treatment of cerebral thrombosis, we should therefore consider not only antiplatelet effects and anticoagulation but also such increase in t-PA.

Journal

  • Nosotchu

    Nosotchu 19(5), 366-372, 1997

    The Japan Stroke Society

Codes

  • NII Article ID (NAID)
    130003631293
  • Text Lang
    JPN
  • ISSN
    0912-0726
  • Data Source
    J-STAGE 
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