Transplant Biomedicals S.L., Barcelona 08042, Spain.
Institut d'Investigacions Biomèdiques August Pi I Sunyer (IDIBAPS), Barcelona 08036, Spain.
Int J Mol Sci. 2019 Apr 10;20(7):1785. doi: 10.3390/ijms20071785.
We analyzed the participation of mitogen-activated protein kinases (MAPKs), namely p38, JNK and ERK 1/2 in steatotic and non-steatotic livers undergoing ischemia-reperfusion (I-R), an unresolved problem in clinical practice. Hepatic steatosis is a major risk factor in liver surgery because these types of liver tolerate poorly to I-R injury. Also, a further increase in the prevalence of steatosis in liver surgery is to be expected. The possible therapies based on MAPK regulation aimed at reducing hepatic I-R injury will be discussed. Moreover, we reviewed the relevance of MAPK in ischemic preconditioning (PC) and evaluated whether MAPK regulators could mimic its benefits. Clinical studies indicated that this surgical strategy could be appropriate for liver surgery in both steatotic and non-steatotic livers undergoing I-R. The data presented herein suggest that further investigations are required to elucidate more extensively the mechanisms by which these kinases work in hepatic I-R. Also, further researchers based in the development of drugs that regulate MAPKs selectively are required before such approaches can be translated into clinical liver surgery.
我们分析了丝裂原活化蛋白激酶（MAPK），即 p38、JNK 和 ERK1/2 在脂肪肝和非脂肪肝肝脏缺血再灌注（I-R）中的作用，这是临床实践中尚未解决的问题。肝脂肪变性是肝外科的一个主要危险因素，因为这类肝脏对 I-R 损伤的耐受性较差。此外，预计肝外科中脂肪变性的患病率还会进一步增加。我们将讨论基于 MAPK 调节的可能治疗方法，以减少肝 I-R 损伤。此外，我们还回顾了 MAPK 在缺血预处理（PC）中的相关性，并评估了 MAPK 调节剂是否可以模拟其益处。临床研究表明，这种手术策略可能适用于 I-R 期间的脂肪肝和非脂肪肝肝脏的肝外科手术。本文提供的数据表明，需要进一步研究以更广泛地阐明这些激酶在肝 I-R 中发挥作用的机制。此外，在这些方法转化为临床肝外科之前，需要更多的研究人员致力于开发选择性调节 MAPKs 的药物。
