2022 Fiscal Year Final Research Report
Analysis to elucidate the pathogenesis of thrombotic microangiopathy and improve graft function after living donor liver transplantation
| Project/Area Number |
19K18111
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 55020:Digestive surgery-related
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| Research Institution | Mie University |
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Principal Investigator |
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| Project Period (FY) |
2019-04-01 – 2023-03-31
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| Keywords | 血栓性微小血管障害 / 生体肝移植 / 肝虚血再還流障害 |
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| Outline of Final Research Achievements |
Thrombotic microangiopathy is one of the cause of graft failure after living donor liver transplantation. In mice liver ischemia-reperfusion injury (IRI) model, we evaluated the efficacy of ADAMTS13, which was a cleavage enzyme of von Willebrand Factor, in liver IRI. However, there was no significant efficacy. Therefore, we administered FXa inhibitor, edoxaban, as anticoagulant agent.
Postoperative liver injury was alleviated. As anticoagulant effect, sinusoidal congestion was improved in the live tissue. Moreover, inflammatory cytokines and chemokines were reduced, and the infiltration of inflammatory cells into liver tissue was attenuated. Apoptosis of hepatocyte was also prevented. FXa protected liver IRI by these anticoagulant, anti-inflammatory and anti-apoptotic effects.
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| Free Research Field |
肝胆膵・移植外科学
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| Academic Significance and Societal Importance of the Research Achievements |
本邦では肝移植の約9割が生体肝移植である。部分肝である生体肝移植では術後肝機能の回復に時間を要する。その中で術後早期のグラフト機能不全は周術期死亡の最も大きな要因である。血栓性微小血管障害症はグラフト肝機能不全となる原因の一つであり、移植肝における微小循環を改善することが命題である。今回われわれは抗凝固因子の一つであるXa阻害薬が肝虚血再還流障害を軽減させることを示した。またその肝保護効果が本来の抗凝固作用のみならず、抗炎症、抗細胞死作用からも示された。 これらを臨床応用できれば、早期のグラフト肝不全を防ぎ、生体肝移植の成績を向上させる可能性があると考えられた。
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