シムバスタチンは,エンドトキシン誘発性組織因子をin vivoで鈍化する
Sabine Steiner1, Walter S Speidl, Johannes Pleiner
1Second Department of Medicine, Division of Angiology, Medical University of Vienna,Vienna, Austria.
Circulation
|April 13, 2005
まとめ
シムバスタチンは,エンドトキセミア中の炎症と単細胞組織因子 (TF) 発現を減少させます. このスタチン治療は,健康な被験者の血小板活性化に影響を与えませんでした.
科学分野:
- 薬理学 薬理学とは
- 免疫学 免疫学とは
- 心血管医学は,心臓血管医学である.
背景:
- スタチンは,脂質を下げること以外にも,抗炎症的特性を持っています.
- 実験室内研究では,スタチンはリポポリサッカリド (LPS) 誘発の単細胞組織因子 (TF) 発現を阻害することを示唆しています.
- この研究では,実験的なエンドトキシミアにおける炎症および血栓形成反応に対するスタチンの効果を調査しています.
研究 の 目的:
- LPSに対する炎症性および血栓形成反応に対するシムバスタチンのインビボ効果を評価する.
- モノサイトTF発現および関連する炎症マーカーに対するシムバスタチンの影響を評価する.
- シムバスタチンが,エンドトキセミア中の血小板活性化に影響を与えるかどうかを判断する.
主な方法:
- ダブルブラインド・プラセボ対照試験で,健康な男性20人を対象に,シムバスタチンまたはプラセボを4日間ランダムに割り当てました.
- LPSを静脈内投与すると,血のhsCRP,MCP-1,sCD40L,sCD40およびF1.2.2.の測定が行われます.
- 単細胞TF発現と単細胞-血小板集積は全血流細胞測定で評価された.
主要な成果:
- シムバスタチンは,hsCRPとMCP-1におけるLPS誘発の上昇を著しく抑制しました.
- スタチンの治療は,LPSの挑戦後のモノサイトTF発現の上昇を鈍化させた.
- シムバスタチンは,エンドトキシン誘発のプロトロンビン断片F1.2.2.の形成を有意に減少させた.
- LPSの輸注は,単細胞・血小板の集積形成やsCD40/sCD40Lの血レベルを変化させなかった.
結論:
- シムバスタチンは,エンドトキシンに対する炎症反応を in vivo で効果的に抑制します.
- シムバスタチンは,実験的なエンドトキセミア中にモノサイト組織因子の発現を弱める.
- このモデルにおけるスタチンの投与は,血小板活性化に影響を与えませんでした.
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