Elucidation of pathophysiology of Sinusoidal Obstruction Syndrome and development of new prevention and treatment methods

2018 Fiscal Year Final Research Report

• Project/Area Number: 15K10158
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Kanazawa University
• Principal Investigator: Tajima Hidehiro 金沢大学, 附属病院, 講師 (00436825)
• Co-Investigator(Kenkyū-buntansha): 宮下 知治 金沢大学, 附属病院, 助教 (30397210) ; 太田 哲生 金沢大学, 医学系, 教授 (40194170)
• Project Period (FY): 2015-04-01 – 2019-03-31
• Keywords: 肝類洞閉塞症候群 / 血小板 / veno-occlusive disease / シロスタゾール

Outline of Final Research Achievements

Chronic rejection after liver transplantation, anticancer agents such as oxaliplatin, and hematopoietic stem cell transplantation are cause sinusoid obstruction syndrome (SOS) characterized by splenomegaly and thrombocytopenia, resulting in liver dysfunction. SOS have the common feature of progressing chronically around the central vein (zone 3). If it is hypothesized that extravascular platelet aggregation in the Disse’s space cause of SOS, it will be possible to unify the series of pathogenesis that accompanies SOS. In this study, we aimed to confirm the state of platelet aggregation with rat SOS model and to examine the preventive effect of antiplatelet drug on SOS. We made rat SOS model with monocrotaline and discovered the presence of platelet aggregation in the Disse’s space around central vein (zone 3) with immunohistological examination and electron microscopy, and also certified that antiplatelet drug (cilostazol) has preventive effect for SOS.

Free Research Field

肝胆膵・移植外科学

Academic Significance and Societal Importance of the Research Achievements

血小板は核を持たないため、通常のHE染色では組織内での存在を確認することができず、その重要性は認識されながらもこれまで研究が進展してこなかった。血小板からは様々な成長因子が分泌されることが知られており、血小板が原因であると仮定するとSOS以外にも敗血症時の肝障害や癌の転移など様々な病態を説明することができることから、今後の研究の発展が期待される。