Covington Stephen M, Bauler Laura D, Toledo-Pereyra Luis H
a Michigan State University College of Osteopathic Medicine , East Lansing, Michigan , USA.
b Division of Epidemiology and Biostatistics , Western Michigan University Homer Stryker M.D. School of Medicine , Kalamazoo , Michigan , USA.
J Invest Surg. 2017 Feb;30(1):47-55. doi: 10.1080/08941939.2016.1206999. Epub 2016 Jul 27.
Liver transplantation is the second most common transplant procedure in the United States. A leading cause of post-transplantation organ dysfunction is I/R injury. During I/R injury, the serine/threonine kinase Akt is activated, stimulating downstream mediators to promote cellular survival. Due to the cellular effects of Akt, therapeutic manipulation of the Akt pathway can help reduce cellular damage during hepatic I/R that occurs during liver transplantation.
A full description of therapeutic options available that target Akt to reduce hepatic I/R injury has not been addressed within the literature. The purpose of this review is to illuminate advances in the manipulation of Akt that can be used to therapeutically target I/R injury in the liver.
An in depth literature review was performed using the Scopus and PubMed databases. A total of 75 published articles were utilized for this manuscript. Terminology searched includes a combination of "hepatic ischemia/reperfusion injury", "Akt/PKB", "preconditioning" and "postconditioning."
Four principal methods that reduce I/R injury include hepatic pre- and postconditioning, pharmacological intervention and future miRNA/gene therapy. Discussed therapies used serum alanine aminotransferase levels, liver histology and phosphorylation of downstream mediators to confirm the Akt protective effect.
The activation of Akt from the reviewed therapies has resulted in predictable reduction in hepatocyte damage using the previously mentioned measurements. In a clinical setting, these therapies could potentially be used in combination to achieve better outcomes in hepatic transplant patients. Evidence supporting reduced I/R injury through Akt activation warrants further studies in human clinical trials.
肝移植是美国第二常见的移植手术。移植后器官功能障碍的一个主要原因是缺血/再灌注损伤（I/R损伤）。在I/R损伤期间，丝氨酸/苏氨酸激酶Akt被激活，刺激下游介质以促进细胞存活。由于Akt的细胞效应，对Akt通路进行治疗性调控有助于减少肝移植期间发生的肝脏I/R损伤时的细胞损伤。
文献中尚未对靶向Akt以减少肝脏I/R损伤的现有治疗选择进行全面描述。本综述的目的是阐明在调控Akt方面取得的进展，这些进展可用于对肝脏I/R损伤进行治疗性靶向。
使用Scopus和PubMed数据库进行了深入的文献综述。本手稿共使用了75篇已发表的文章。搜索的术语包括“肝脏缺血/再灌注损伤”、“Akt/PKB”、“预处理”和“后处理”的组合。
减少I/R损伤的四种主要方法包括肝脏预处理和后处理、药物干预以及未来的微小RNA/基因治疗。所讨论的治疗方法使用血清丙氨酸转氨酶水平、肝脏组织学以及下游介质的磷酸化来证实Akt的保护作用。
使用上述测量方法，所综述治疗方法中Akt的激活已导致肝细胞损伤得到可预测的减少。在临床环境中，这些治疗方法可能联合使用，以在肝移植患者中取得更好的结果。支持通过激活Akt减少I/R损伤的证据值得在人类临床试验中进一步研究。
