Novel therapeutic strategy for hepatic ischemia-reperfusion injury based on ADAMTS13-related factors

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K18100
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 55020:Digestive surgery-related
• Research Institution: Nara Medical University
• Principal Investigator: Yoshikawa Takahiro 奈良県立医科大学, 医学部附属病院, 研究員 (80773275)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: ADAMTS13 / 肝切除

Outline of Final Research Achievements

Introduction : von Willebrand factor (VWF) is synthesised in vascular endothelial cells and released into the plasma as unusually large VWF multimers (UL-VWFMs). Sinusoidal endothelial cells are a major target of ischaemia reperfusion injury due to liver surgery. This study aimed to clarify the effect of hepatectomy on ULVWFMs. Results : By multivariable analysis, Pringle's maneuver duration was significantly associated with increased UL-VWFMs level after hepatectomy[odds ratio 1.049, p=0.043]. UL-VWFMs index was significantly correlated with Pringle's maneuver duration (r=0.444,p=0.017).Conclusions : Plasma UL-VWFMs levels increased after hepatectomy due to ischaemia reperfusion injury with Pringle's maneuver.

Free Research Field

肝臓外科

Academic Significance and Societal Importance of the Research Achievements

本研究で肝切除中のPringle法が血管内皮細胞傷害を惹起し，VWFマルチマーが増加することで，肝内に病的血栓が形成され易い状態にあることが示された．
今まで虚血再灌流障害に対する治療法として，肝切除とADAMTS13関連因子に着目した検討は，国内外において報告がない．本研究はADAMTS13関連因子という観点から，術中Pringle法による虚血再灌流障害のメカニズムを解明することで，肝切除後肝不全に対する新たな治療戦略を創生することを目的とし，今後研究がすすめば，新たな肝切除後肝不全治療戦略となる可能性がある．