Zhongnan Hospital of Wuhan University, Institute of Hepatobiliary Diseases of Wuhan University, Transplant Center of Wuhan University, Hubei Key Laboratory of Medical Technology on Transplantation, Wuhan, Hubei 430071, China.
Research Center of National Health Ministry on Transplantation Medicine Engineering and Technology, The 3rd Xiangya Hospital of Central South University, Changsha, Hunan 410013, China.
Oxid Med Cell Longev. 2017;2017:3861914. doi: 10.1155/2017/3861914. Epub 2017 Nov 19.
Severe hepatic ischemia reperfusion injury (IRI) can result in poor short- and long-term graft outcome after transplantation. The way to improve the viability of livers from donors after circulatory death (DCD) is currently limited. The aim of the present study was to explore the protective effect of simvastatin on DCD livers and investigate the underlying mechanism.
24 male rats randomly received simvastatin or its vehicle. 30 min later, rat livers were exposed to warm ischemia in situ for 30 min. Livers were removed and cold-stored in UW solution for 24 h, subsequently reperfused for 60 min with an isolated perfused rat liver system. Liver injury was evaluated during and after warm reperfusion.
Pretreatment of DCD donors with simvastatin significantly decreased IRI liver enzyme release, increased bile output and ATP, and ameliorated hepatic pathological changes. Simvastatin maintained the expression of KLF2 and its protective target genes (eNOS, TM, and HO-1), reduced oxidative stress, inhibited innate immune responses and inflammation, and increased the expression of Bcl-2/Bax to suppress hepatocyte apoptosis compared to DCD control group.
Pretreatment of DCD donors with simvastatin improves DCD livers' functional recovery probably through a KLF2-dependent mechanism. These data suggest that simvastatin may provide a potential benefit for clinical DCD liver transplantation.
严重的肝脏缺血再灌注损伤（IRI）可导致移植后供体肝脏的短期和长期移植物结局不佳。目前，提高循环死亡（DCD）供体肝脏活力的方法有限。本研究旨在探讨辛伐他汀对 DCD 肝脏的保护作用，并探讨其潜在机制。
24 只雄性大鼠随机接受辛伐他汀或其载体。30 分钟后，大鼠肝脏在原位暴露于 30 分钟的热缺血中。肝脏被取出并在 UW 溶液中冷储存 24 小时，随后用离体灌注大鼠肝脏系统再灌注 60 分钟。在热再灌注期间和之后评估肝损伤。
辛伐他汀预处理 DCD 供体显著降低了 IRI 肝酶释放，增加了胆汁产量和 ATP，并改善了肝组织学变化。与 DCD 对照组相比，辛伐他汀维持了 KLF2 及其保护性靶基因（eNOS、TM 和 HO-1）的表达，减少了氧化应激，抑制了固有免疫反应和炎症，并增加了 Bcl-2/Bax 的表达，从而抑制了肝细胞凋亡。
辛伐他汀预处理 DCD 供体可改善 DCD 肝脏的功能恢复，可能通过 KLF2 依赖的机制。这些数据表明，辛伐他汀可能为临床 DCD 肝移植提供潜在益处。
