Department of Medical Sciences, University of East Piedmont "A. Avogadro", Via Solaroli 17, 28100 Novara, Italy.
World J Gastroenterol. 2010 Dec 28;16(48):6058-67. doi: 10.3748/wjg.v16.i48.6058.
Ischemia/reperfusion (I/R) injury still represents an important cause of morbidity following hepatic surgery and limits the use of marginal livers in hepatic transplantation. Transient blood flow interruption followed by reperfusion protects tissues against damage induced by subsequent I/R. This process known as ischemic preconditioning (IP) depends upon intrinsic cytoprotective systems whose activation can inhibit the progression of irreversible tissue damage. Compared to other organs, liver IP has additional features as it reduces inflammation and promotes hepatic regeneration. Our present understanding of the molecular mechanisms involved in liver IP is still largely incomplete. Experimental studies have shown that the protective effects of liver IP are triggered by the release of adenosine and nitric oxide and the subsequent activation of signal networks involving protein kinases such as phosphatidylinositol 3-kinase, protein kinase C δ/ε and p38 MAP kinase, and transcription factors such as signal transducer and activator of transcription 3, nuclear factor-κB and hypoxia-inducible factor 1. This article offers an overview of the molecular events underlying the preconditioning effects in the liver and points to the possibility of developing pharmacological approaches aimed at activating the intrinsic protective systems in patients undergoing liver surgery.
缺血/再灌注（I/R）损伤仍然是肝手术后发病率的一个重要原因，并限制了边缘供肝在肝移植中的应用。短暂的血流中断后再灌注可保护组织免受随后的 I/R 引起的损伤。这一过程称为缺血预处理（IP），它依赖于内在的保护系统，其激活可以抑制不可逆组织损伤的进展。与其他器官相比，肝脏 IP 具有额外的特征，因为它可以减轻炎症并促进肝脏再生。我们目前对肝脏 IP 中涉及的分子机制的理解仍然很不完整。实验研究表明，肝脏 IP 的保护作用是由腺苷和一氧化氮的释放以及涉及蛋白激酶（如磷脂酰肌醇 3-激酶、蛋白激酶 C δ/ε 和 p38 MAP 激酶）和转录因子（如信号转导和转录激活因子 3、核因子-κB 和缺氧诱导因子 1）的信号网络的激活触发的。本文概述了肝脏预处理效应的分子事件，并指出了在接受肝手术的患者中开发旨在激活内在保护系统的药理学方法的可能性。
