Changes in Plasma Levels of Tissue Plasminogen Activator and Plasminogen Activator Inhibitor-1 in Sepsis with Organ Failure

重症敗血症時の臓器不全の発生には,凝固機能の亢進や血管内皮障害による微小血栓形成,組織循環障害が関与していると考えられているが,線溶機能に関しては明らかにされていない点も多い。今回敗血症時の線溶機能の変動を明らかにするため,systemic inflammatory response syndrome(以下SIRSと略す)の基準を満たす敗血症症例43例において,tissue plasminogen activator(以下t-PAと略す)とplasminogen activator inhibitor-1(以下PAI-1と略す)を測定し,臓器不全を合併した20例と臓器不全を合併しなかった23例の間で比較した。さらに血中interleukin 6(以下IL-6と略す),好中球エラスターゼ(以下PMN-Eと略す)やlactateとt-PAやPAI-1の関係についても検討を行った。その結果,血中PAI-1値は臓器不全を合併した群(540.1±435.3[mean±SDng/ml])が臓器不全を合併しなかった群(52.6±47.5)に比して有意に高値を示した(p<0.01)。一方,血中t-PA値は臓器不全合併群,非合併群ともに上昇のみられない場合が多く,両群の間で有意差は認められなかった。敗血症重症度の程度を反映する血中IL-6値やPMN-E値とPAI-1値の間には正の相関関係が認められた(IL-6: r=0.81, p<0.01; PMN-E: r=0.34, p<0.05)が,t-PAとの間には明らかな関係は認められなかった。また経時的変動をみるとPAI-1はIL-6やPMN-Eの上昇に約1日遅れて変動がみられる場合が多かった。また血中lactateとPAI-1の間には正の相関が認められ(r=0.70, p<0.01), PAI-1と組織循環障害との関連性が示唆された。以上の結果から,敗血症時には炎症性メディエータによる刺激でPAI-1値が上昇し,線溶機能が抑制されるものと考えられた。この線溶機能低下は血栓形成などによる組織循環障害を助長し,臓器不全に至る準備状態を形成しているものと考えられた。

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