Study of down-regulation of plasma free hemoglobin during therapeutic hypothermia

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K10755
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Cardiovascular surgery
• Research Institution: Shimane University
• Principal Investigator: Oda Teiji 島根大学, 学術研究院医学・看護学系, 教授 (50448198)
• Co-Investigator(Kenkyū-buntansha): 松本 健一 島根大学, 学術研究院医学・看護学系, 教授 (30202328) ; 今井 健介 島根大学, 学術研究院医学・看護学系, 助教 (60457182) ; 末廣 章一 島根大学, 学術研究院医学・看護学系, 助教 (90596545)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: ヘモグロビン / 低体温 / 溶血 / 体外循環

Outline of Final Research Achievements

Extracorporeal circulation causes hemolysis, resulting into increased free hemoglobin. This plasma free hemoglobin can work for a toxic oxidant and induce acute kidney and lung injury. We have previously demonstrated that hypothermia can decrease plasma free hemoglobin levels during therapeutic hypothermia in resuscitated patients after cardiac arrest for the first time. In this study, we have demonstrated that hemoglobin can bind to haptoglobin-related protein (HPR), protein asteroid homolog 1 (ASTE1) and proteasome subunit beta-1 (PSMB1) as well as haptoglobin, a well-known scavenger protein by biotinylated protein interaction pull-down assay and co-immunoprecipitation assay. Among these proteins, only both ASTE1 and PSMB1 have interacted hemoglobin protein during hypothermia (34℃) and normothermia (36℃）. Future study will search for detailed mechanisms scavenging hemoglobin protein.

Free Research Field

心臓血管外科学

Academic Significance and Societal Importance of the Research Achievements

本研究成果をさらに発展させれば、血中遊離ヘモグロビンに対する新しい中和剤を開発できるため、体外循環治療を受ける患者群（心臓大血管手術を受ける患者、血液透析を受ける患者）に対して血中遊離ヘモグロビンの有害作用を減少させる治療法を提供できるようになる。