Prophylactic and therapeutic strategy based on the molecular pathology of septic disseminated intravascular coagulation (DIC)

We used the cecal ligation and puncture (CLP)-induced sepsis mouse model. In septic mice, the mRNA expression levels of tissue factor (TF) and plasminogen activator inhibitor 1 (PAI-1) were greatly increased. In addition, the number of platelets in CLP-induced septic mice were markedly reduced and prothrombin time was significantly prolonged in CLP mice in comparison with controls. These results imply that CLP-induced sepsis is a relevant model of sepsis-associated disseminated intravascular coagulation (DIC). Transfection of NF-κB decoy oligodeoxynucleotides via intravenous injection, when given 1 h after CLP, resulted in a striking reduction in the DNA binding of NF-κB in lungs at 6 h and strongly inhibited elevations in blood levels of pro-inflammatory cytokines in CLP mice. However, NF-κB decoy transfection failed to affect the changes in measures as DIC in CLP mice, suggesting no involvement of the transcription factor NF-κB in the molecular mechanisms underlying septic DIC.

本研究により，盲腸結紮穿孔敗血症マウスは敗血症性DIC病態を研究するうえでよいモデルであることを明らかにした。本研究は，敗血症によるDICの分子病態機構の解明に新たな展開を与えるとともに，現時点で確立されたよい治療法の全くない本病態において，新たなDIC発症予防の開発を模索していくうえでも意義のある研究となったと考えられる。