Shimizu K, Miyagi S, Miyazawa K, Maida K, Kashiwadate T, Hara Y, Goto M, Kawagishi N, Ohuchi N
Division of Advanced Surgical Science and Technology, Graduate School of Medicine, Tohoku University, Sendai, Japan.
Division of Advanced Surgical Science and Technology, Graduate School of Medicine, Tohoku University, Sendai, Japan.
Transplant Proc. 2016 May;48(4):1221-5. doi: 10.1016/j.transproceed.2015.11.031.
Successful liver transplantation from non-heart-beating donors (NHBDs) might enlarge donor source. Some studies have reported that resveratrol (RES), an activator of sirtuins, has cytoprotective effects on ischemia-reperfusion (I/R) injury. The purpose of this study was to investigate the effects of RES on warm I/R injury in rats.
Male Wister rats were divided into 5 groups: (1) the heart-beating (HB) group, whose livers were retrieved from HB donors; (2) the NHB group, whose livers were retrieved under apnea-induced NHB conditions; (3) the ethanol group, retrieved in the same manner as the NHB group with ethanol (10 μL) as a solvent; (4) the RES-1 group, retrieved in the same manner as the NHB group and pretreated with RES (0.4 mg/kg, dissolved in 10 μL ethanol); and (5) the RES-2 group, retrieved in the same manner as the NHB group and pretreated with RES (2 mg/kg, dissolved in 10 μL ethanol). The resected livers were perfused for 60 minutes with Krebs-Henseleit bicarbonate buffer after 6 hours of cold preservation, after which the perfusate and liver tissues were investigated.
The bile production, portal vein flow volume, tumor necrosis factor-α level, and adenosine triphosphate level in the RES-2 group were significantly improved compared with in the NHB group. Histology revealed numerous well-preserved sinusoidal endothelial cells in the RES-2 group.
RES might reduce warm I/R injury and improve the viability of liver grafts from NHBDs. We considered that this method may represent a promising approach for clinical liver transplantation from NHBDs.
非心脏跳动供体(NHBDs)肝移植成功可能会扩大供体来源。一些研究报告称,白藜芦醇(RES)作为一种沉默调节蛋白激活剂,对缺血再灌注(I/R)损伤具有细胞保护作用。本研究旨在探讨RES对大鼠热缺血再灌注损伤的影响。
雄性Wistar大鼠分为5组:(1)心脏跳动(HB)组,其肝脏取自HB供体;(2)NHB组,其肝脏在呼吸暂停诱导的NHB条件下获取;(3)乙醇组,与NHB组获取方式相同,以乙醇(10μL)作为溶剂;(4)RES-1组,与NHB组获取方式相同,并用RES(0.4mg/kg,溶于10μL乙醇)预处理;(5)RES-2组,与NHB组获取方式相同,并用RES(2mg/kg,溶于10μL乙醇)预处理。切除的肝脏在冷保存6小时后用Krebs-Henseleit碳酸氢盐缓冲液灌注60分钟,之后对灌注液和肝组织进行检测。
与NHB组相比,RES-2组的胆汁生成、门静脉血流量、肿瘤坏死因子-α水平和三磷酸腺苷水平均显著改善。组织学检查显示RES-2组有大量保存良好的肝窦内皮细胞。
RES可能减轻热缺血再灌注损伤并提高NHBDs肝移植的活力。我们认为这种方法可能是临床NHBDs肝移植的一种有前景的方法。