Robertson Francis P, Fuller Barry J, Davidson Brian R
Division of Surgery and Interventional Science, Royal Free Campus, University College London, 9th Floor, Royal Free Hospital, Pond Street, London NW3 2QG, UK.
Department of Hepaticopancreatobiliary Surgery and Liver Transplantation, Royal Free Foundation Trust, 9th Floor, Royal Free Hospital, Pond Street, London NW3 2QG, UK.
J Clin Med. 2017 Jul 14;6(7):69. doi: 10.3390/jcm6070069.
Liver Ischaemia Reperfusion (IR) injury is a major cause of post-operative liver dysfunction, morbidity and mortality following liver resection surgery and transplantation. There are no proven therapies for IR injury in clinical practice and new approaches are required. Ischaemic Preconditioning (IPC) can be applied in both a direct and remote fashion and has been shown to ameliorate IR injury in small animal models. Its translation into clinical practice has been difficult, primarily by a lack of knowledge regarding the dominant protective mechanisms that it employs. A review of all current studies would suggest that IPC/RIPC relies on creating a small tissue injury resulting in the release of adenosine and l-arginine which act through the Adenosine receptors and the haem-oxygenase and endothelial nitric oxide synthase systems to reduce hepatocyte necrosis and improve the hepatic microcirculation post reperfusion. The next key step is to determine how long the stimulus requires to precondition humans to allow sufficient injury to occur to release the potential mediators. This would open the door to a new therapeutic chapter in this field.
肝脏缺血再灌注(IR)损伤是肝切除手术和肝移植术后肝功能障碍、发病率和死亡率的主要原因。在临床实践中,尚无经证实的针对IR损伤的治疗方法,因此需要新的治疗方法。缺血预处理(IPC)可以直接和远程应用,并且已被证明可减轻小动物模型中的IR损伤。将其转化为临床实践一直很困难,主要是因为缺乏对其主要保护机制的了解。对所有当前研究的综述表明,IPC/RIPC依赖于造成轻微的组织损伤,从而导致腺苷和L-精氨酸的释放,它们通过腺苷受体以及血红素加氧酶和内皮型一氧化氮合酶系统发挥作用,以减少肝细胞坏死并改善再灌注后的肝微循环。下一个关键步骤是确定刺激人类进行预处理所需的时间,以使足够的损伤发生以释放潜在的介质。这将为该领域开启新的治疗篇章。