Alchera Elisa, Imarisio Chiara, Mandili Giorgia, Merlin Simone, Chandrashekar Bangalore R, Novelli Francesco, Follenzi Antonia, Carini Rita
Department of Health Science, University of Piemonte Orientale, 28100 Novara, Italy.
Centre for Experimental and Clinical Studies (CERMS), Azienda Universitaria Ospedaliera Città della Salute e della Scienza Città di Torino, 10100 Turin, Italy ; Department of Molecular Biotechnology and Heath Sciences, University of Turin, 10100 Turin, Italy.
Biomed Res Int. 2015;2015:286746. doi: 10.1155/2015/286746. Epub 2015 Oct 11.
Ischemic preconditioning (IP) of the liver by a brief interruption of the blood flow protects the damage induced by a subsequent ischemia/reperfusion (I/R) preventing parenchymal and nonparenchymal liver cell damage. The discovery of IP has shown the existence of intrinsic systems of cytoprotection whose activation can stave off the progression of irreversible tissue damage. Deciphering the molecular mediators that underlie the cytoprotective effects of preconditioning can pave the way to important therapeutic possibilities. Pharmacological activation of critical mediators of IP would be expected to emulate or even to intensify its salubrious effects. In vitro and in vivo studies have demonstrated the role of the adenosine A2a receptor (A2aR) as a trigger of liver IP. This review will provide insight into the phenotypic changes that underline the resistance to death of liver cells preconditioned by pharmacological activation of A2aR and their implications to develop innovative strategies against liver IR damage.
肝脏短暂血流中断进行的缺血预处理（IP）可保护后续缺血/再灌注（I/R）诱导的损伤，防止肝实质细胞和非实质细胞损伤。IP的发现表明存在内在的细胞保护系统，其激活可延缓不可逆组织损伤的进展。破解预处理细胞保护作用背后的分子介质可为重要的治疗可能性铺平道路。预计IP关键介质的药理学激活将模拟甚至增强其有益作用。体外和体内研究已证明腺苷A2a受体（A2aR）作为肝脏IP触发因素的作用。本综述将深入探讨通过A2aR药理学激活预处理的肝细胞对死亡产生抗性的表型变化及其对开发抗肝脏IR损伤创新策略的意义。
