Control mechanisms and its failure of endothelial hyperpermeability in sepsis: from a view point of erythrocyte and platelet

Research Project

Project/Area Number	15K11000
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Research Field	Emergency medicine
Research Institution	Kurume University
Principal Investigator	Takasu Osamu 久留米大学, 医学部, 教授 (90236216)
Co-Investigator(Kenkyū-buntansha)	新山修平久留米大学, 医学部, 准教授 (40258455)
Project Period (FY)	2015-04-01 – 2018-03-31
Project Status	Completed (Fiscal Year 2017)
Budget Amount *help	¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000) Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000) Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000) Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Keywords	敗血症 / 臓器不全 / 血管透過性亢進 / CLP / バイオインピーダンス法 / VE-カドヘリン / Angiopoietin-1 / 盲腸結紮穿孔モデル / カドヘリン / 赤血球変形能
Outline of Final Research Achievements	Endothelial hyper permeability is attracted attention as one of the mechanisms of the organ failure in critically ill patients. The purpose of this study was to clarify the potential of platelets or erythrocytes as modulator of the endothelial hyperpermeability. On the cecal ligation and puncture (CLP) model of mice, there was a positive correlation between the sVE-Cadherin and the extracellular water ratio (ECW% ratio) measured by bioimpedance analysis. The characteristic changes of platelets were prominent than that of erythrocytes in early phase of sepsis. Angiopoietin-1, which acts as a positive regulating factor for VE-cadherin, decreased depending the number of platelets. Administration of the platelet rich plasma (PRP) extraction containing abundant Ang-1 suppressed increase in the ECW% on CLP mice. These findings suggested that a therapeutic potential of PRP extraction for endothelial hyperpermeability.