Miyashita T, Nakanuma S, Ahmed A K, Makino I, Hayashi H, Oyama K, Nakagawara H, Tajima H, Takamura H, Ninomiya I, Fushida S, Harmon J W, Ohta T
Department of Gastroenterological Surgery, Kanazawa University Hospital, 13-1 Takaramachi, 920-8641 Kanazawa, Ishikawa Japan.
Department of Surgery, Johns Hopkins University School of Medicine, 4940 Eastern Avenue, 21224 Baltimore, MD USA.
Eur Surg. 2016;48:92-98. doi: 10.1007/s10353-015-0363-3. Epub 2015 Oct 14.
The exact sequence of events leading to ultimate hepatocellular damage following ischemia/reperfusion (I/R) is incompletely understood. In this article, we review a mechanism of organ dysfunction after hepatic I/R or immunosuppressive treatment, in addition to the potential of liver sinusoidal endothelial cell (LSEC) protection and antiplatelet treatment for the suppression of hepatocellular damage.
A review of the literature, utilizing PubMed-NCBI, was used to provide information on the components necessary for the development of hepatocellular damage following I/R.
It is well-established that LSECs damage following hepatic I/R or immunosuppressive treatment followed by extravasated platelet aggregation (EPA) is the root cause of organ dysfunction in liver transplantation. We have classified three phases, from LSECs damage to organ dysfunction, utilizing the predicted pathogenic mechanism of sinusoidal obstruction syndrome. The first phase is detachment of LSECs and sinusoidal wall destruction after LSECs injury by hepatic I/R or immunosuppressive treatment. The second phase is EPA, accomplished by sinusoidal wall destruction. The various growth factors, including thromboxane A2, serotonin, transforming growth factor-beta and plasminogen activator inhibitor-1, released by EPA in the Disse's space of zone three, induce portal hypertension and the progression of hepatic fibrosis. The third phase is organ dysfunction following portal hypertension, hepatic fibrosis, and suppressed liver regeneration through various growth factors secreted by EPA.
We suggest that EPA in the space of Disse, initiated by LSECs damage due to hepatic I/R or immunosuppressive treatment, and activated platelets may primarily contribute to liver damage in liver transplantation. Endothelial protective therapy or antiplatelet treatment may be useful in the treatment of hepatic I/R following EPA.
缺血/再灌注（I/R）后导致最终肝细胞损伤的确切事件顺序尚未完全明了。在本文中，我们除了回顾肝I/R或免疫抑制治疗后器官功能障碍的机制，以及肝窦内皮细胞（LSEC）保护和抗血小板治疗对抑制肝细胞损伤的潜力外，还将进行相关阐述。
利用PubMed-NCBI对文献进行综述，以提供有关I/R后肝细胞损伤发展所需成分的信息。
公认的是，肝I/R或免疫抑制治疗后LSECs损伤，随后发生血管外渗性血小板聚集（EPA），是肝移植中器官功能障碍的根本原因。我们利用窦性阻塞综合征的预测致病机制，将从LSECs损伤到器官功能障碍分为三个阶段。第一阶段是肝I/R或免疫抑制治疗导致LSECs损伤后，LSECs脱离和肝窦壁破坏。第二阶段是EPA，由肝窦壁破坏引起。EPA在肝小叶三区的狄氏间隙释放的各种生长因子，包括血栓素A2、5-羟色胺、转化生长因子-β和纤溶酶原激活物抑制剂-1，可导致门静脉高压和肝纤维化进展。第三阶段是门静脉高压、肝纤维化以及通过EPA分泌的各种生长因子抑制肝再生后出现的器官功能障碍。
我们认为，由肝I/R或免疫抑制治疗导致的LSECs损伤引发的狄氏间隙内的EPA以及活化的血小板，可能是肝移植中肝损伤的主要原因。内皮保护疗法或抗血小板治疗可能对EPA后的肝I/R治疗有用。
