Analysis of promoting factor of liver regeneration in ALPPS

Research Project

Project/Area Number	17K10664
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Research Field	Digestive surgery
Research Institution	Shinshu University
Principal Investigator	Shimizu Akira 信州大学, 学術研究院医学系(医学部附属病院), 講師 (00447773)
Co-Investigator(Kenkyū-buntansha)	本山博章信州大学, 学術研究院医学系(医学部附属病院), 助教 (20569587) 宮川眞一信州大学, 医学部, 特任教授 (80229806) 小林聡信州大学, 学術研究院医学系, 准教授 (90334903)
Project Period (FY)	2017-04-01 – 2020-03-31
Project Status	Completed (Fiscal Year 2019)
Budget Amount *help	¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000) Fiscal Year 2019: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000) Fiscal Year 2018: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000) Fiscal Year 2017: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Keywords	ALPPS / NOS / NO誘導 / 肝再生 / 外科
Outline of Final Research Achievements	Although Associating Liver Partition and Portal vein ligation for Staged hepatectomy (ALPPS) has been reported to achieve future liver remnant liver (FLR) hypertrophy in a short period, the underlying mechanisms are unclear. We established rat portal vein ligation (PVL) model, ALPPS (ALP) model, and hepatectomy model (in which ischemic liver area was resected after ALPPS), and assess the relationship between activation or inhibition of eNOS and liver regeneration in FLR. Since inhibition of eNOS suppressed liver regeneration and activation of eNOS enhanced liver regeneration in FLR, eNOS activation might be pivotal for accelerated FLR regeneration after ALPPS.
Academic Significance and Societal Importance of the Research Achievements	ALPPS手術に関して，肝血流動態やeNOS活性化に着目した基礎研究報告はなく，本研究は極めて独創的であると考えられる．本研究の意義は，ALPPS手術でみられる迅速な肝再生促進因子を同定しその解析を行うことにより，(1) 現存する治療法よりも効率的な肝再生と代償性肥大を促す治療法の開発により，大量肝切除後の肝不全リスクを低減し，肝胆道癌手術の安全性・確実性の向上に貢献する点，(2) 肝移植以外に治療選択肢のない肝不全症例において，将来的に既存の肝細胞・肝組織の再生を促す移植代替療法，もしくは肝機能を維持し移植待機可能期間の延長をもたらす中継療法を開発するための端緒となりうる点，にある．