Ischemia reperfusion-facilitated sinusoidal endothelial cell injury in liver transplantation and the resulting impact of extravasated platelet aggregation.
Ischemia reperfusion-facilitated sinusoidal endothelial cell injury in liver transplantation and the resulting impact of extravasated platelet aggregation.
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DOI：
10.1007/s10353-015-0363-3
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发表时间：
2016
期刊：
影响因子：
--
通讯作者：
Ohta T
中科院分区：
文献类型：
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作者：
Miyashita T;Nakanuma S;Ahmed AK;Makino I;Hayashi H;Oyama K;Nakagawara H;Tajima H;Takamura H;Ninomiya I;Fushida S;Harmon JW;Ohta T
缺血/再灌注（I/R）后导致最终肝细胞损伤的事件的确切顺序尚不完全清楚。在这篇文章中，我们回顾了肝脏I/R或免疫抑制剂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抑制肝细胞损伤的潜力。使用PubMed-NCBI进行文献综述，以提供I/R后肝细胞损伤发展所需的成分信息。众所周知，肝I/R或免疫抑制剂治疗后的LSECs损伤以及随后的外渗血小板聚集（EPA）是肝移植中器官功能障碍的根本原因。我们已经分类三个阶段，从LSECs损害器官功能障碍，利用预测的发病机制窦阻塞综合征。第一阶段是肝I/R或免疫抑制剂治疗导致LSEC损伤后LSEC脱离和窦壁破坏。第二阶段是EPA，通过正弦壁破坏完成。EPA在第三区的Disse间隙中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，诱导门静脉高压和肝纤维化的进展。第三阶段是门静脉高压、肝纤维化和通过EPA分泌的各种生长因子抑制的肝再生后的器官功能障碍。我们认为，EPA在空间的Disse，启动LSECs损伤由于肝I/R或免疫抑制剂治疗，活化血小板可能主要有助于肝移植中的肝损伤。内皮保护治疗或抗血小板治疗可能有助于EPA后肝I/R的治疗。
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.