Experimental Transplantation Surgery, Department of General, Visceral, and Vascular Surgery, Jena University Hospital, Jena, Germany.
Department of Obstetrics and Gynecology, Wuhan Central Hospital, Wuhan, China.
Transplantation. 2018 Mar;102(3):368-377. doi: 10.1097/TP.0000000000001999.
Because of the lack of adequate organs, the number of patients with end-stage liver diseases, acute liver failure or hepatic malignancies waiting for liver transplantation is constantly increasing. Accepting aged liver grafts is one of the strategies expanding the donor pool to ease the discrepancy between the growing demand and the limited supply of donor organs. However, recipients of organs from old donors may show an increased posttransplantation morbidity and mortality due to enhanced ischemia-reperfusion injury. Energy metabolism, inflammatory response, and autophagy are 3 critical processes which are involved in the aging progress as well as in hepatic ischemia-reperfusion injury. Compared with young liver grafts, impairment of energy metabolism in aged liver grafts leads to lower adenosine triphosphate production and an enhanced generation of free radicals, both aggravating the inflammatory response. The aggravated inflammatory response determines the extent of hepatic ischemia-reperfusion injury and augments the liver damage. Autophagy protects cells by removal of damaged organelles, including dysfunctional mitochondria, a process impaired in aging and involved in ischemia-reperfusion-related apoptotic cell death. Furthermore, autophagic degradation of cellular compounds relieves intracellular adenosine triphosphate level for the energy depressed cells. Strategies targeting the mechanisms involved in energy metabolism, inflammatory response, and autophagy might be especially useful to prevent the increased risk for ischemia-reperfusion injury in aged livers after major hepatic surgery.
由于缺乏足够的器官，等待肝移植的终末期肝病、急性肝衰竭或肝恶性肿瘤患者的数量不断增加。接受老年供肝是扩大供者库以缓解不断增长的需求与有限的供体器官供应之间差距的策略之一。然而，由于增强的缺血再灌注损伤，老年供者器官的受者可能表现出增加的移植后发病率和死亡率。能量代谢、炎症反应和自噬是参与衰老过程以及肝缺血再灌注损伤的 3 个关键过程。与年轻供肝相比，老年供肝的能量代谢受损导致三磷酸腺苷产生减少和自由基生成增加，两者均加重炎症反应。加重的炎症反应决定了肝缺血再灌注损伤的程度，并加重了肝损伤。自噬通过去除受损的细胞器（包括功能失调的线粒体）来保护细胞，这一过程在衰老过程中受损，并参与与缺血再灌注相关的细胞凋亡。此外，细胞化合物的自噬降解为能量不足的细胞释放细胞内三磷酸腺苷水平。针对能量代谢、炎症反应和自噬机制的策略可能特别有助于预防大型肝手术后老年肝脏缺血再灌注损伤的风险增加。
