Comprehensive Understanding of Liver Tissue for Curative Treatment of Liver Diseases and Development of Liver Regeneration Therapies

2023 Fiscal Year Final Research Report

• Project/Area Number: 20K17678
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 55020:Digestive surgery-related
• Research Institution: Shinshu University
• Principal Investigator: Yasukawa Koya 信州大学, 医学部, 特任助教 (30868071)
• Project Period (FY): 2020-04-01 – 2024-03-31
• Keywords: ALPPS / 肝再生 / eNOS / 炎症性サイトカイン

Outline of Final Research Achievements

Although the associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) induces more rapid liver regeneration than portal vein embolization, the mechanism remains unclear.
The ALPPS group showed significant FLR regeneration compared with that observed in the PVL group 48 h after surgery. In the ALPPS group, serum interleukin-6 expression was suppressed using GdCl3 to the same extent as that in the PVL group. However, the FLR/BW ratio and Ki-67 labeling index were significantly higher in the ALPPS group administered GdCl3 than in the PVL group. Phospho-Akt Ser473 and phospho-eNOS Ser1177 levels were enhanced in the ALPPS group. In the PVL group treated with molsidomine, the FLR/BW ratio and Ki-67 labeling index increased to the same level as in the ALPPS group.
Early induction of inflammatory cytokines may not be pivotal for accelerated FLR regeneration after ALPPS, whereas Akt-eNOS pathway activation may contribute to accelerated regeneration of the FLR.

Free Research Field

肝胆膵外科学分野

Academic Significance and Societal Importance of the Research Achievements

ALPPS手術における肝の早期再生に関わる因子はいまだ未解明であり、何が重要な因子として寄与しているかをつきとめた研究はない。我々はALPPSモデルならびに従来の門脈結紮法との肝再生に関わる因子を比較・同定するために研究を行った。結果から、従来炎症性サイトカインの早期誘導がALPPS後のFLRの再生促進には重要と考えられていたが、Akt-eNOS経路の活性化はFLRの再生促進に寄与する可能性が考えられた。