Department of Specific Organ Regulation (Urology), Graduate School of Medicine, Osaka University, Osaka, Japan.
Transplantation. 2012 Jul 15;94(1):14-21. doi: 10.1097/TP.0b013e318255f8be.
Renal ischemia-reperfusion (I/R) injury is unavoidable in kidney transplantation and frequently influences both short- and long-term allograft survival rates. One of the major events in I/R injury is the generation of cytotoxic oxygen radicals. Recently, hydrogen gas has been reported to display antioxidant properties and protective effects against organ dysfunction induced by various I/R injuries. We investigated whether hydrogen-rich University of Wisconsin (HRUW) solution attenuates renal cold I/R injury.
We prepared HRUW solution by a novel method involving immersion of centrifuge tubes containing UW solution into hydrogen-saturated water. Hydrogen readily permeates through the centrifuge tubes, and thus, the hydrogen concentration of the UW solution gradually increases in a time-dependent manner. Syngeneic rat kidney transplantation was performed, and the animals were divided into three groups: recipients with nonpreserved grafts (control group), recipients with grafts preserved in UW solution for 24 to 48 hr (UW group), and recipients with grafts preserved in HRUW solution for 24 to 48 hr (HRUW group).
In the early phases, HRUW solution decreased oxidative stress, tubular apoptosis, and interstitial macrophage infiltration in the kidney grafts. Consequently, HRUW solution improved renal function and prolonged recipient survival rate compared with simple cold storage using UW solution. Histopathologically, HRUW treatment alleviated tubular injury and suppressed development of interstitial fibrosis.
HRUW solution improved graft function and prolonged graft survival compared with simple cold storage using UW solution by protecting tubular epithelial cells from inflammation and apoptosis. Our new method of organ preservation is a groundbreaking, safe, and simple strategy that may be applied in the clinical setting.
肾缺血再灌注(I/R)损伤在肾移植中不可避免,经常影响短期和长期移植物存活率。I/R 损伤中的主要事件之一是细胞毒性氧自由基的产生。最近,氢气被报道具有抗氧化特性,并能防止各种 I/R 损伤引起的器官功能障碍。我们研究了富含氢的威斯康星大学(HRUW)溶液是否能减轻肾冷 I/R 损伤。
我们通过一种新的方法制备 HRUW 溶液,将含有 UW 溶液的离心管浸入氢气饱和水中。氢气很容易透过离心管,因此 UW 溶液中的氢气浓度会在时间依赖的方式下逐渐增加。进行同基因大鼠肾移植,将动物分为三组:未保存供体肾的受体(对照组)、保存于 UW 溶液中 24 至 48 小时的供体肾(UW 组)和保存于 HRUW 溶液中 24 至 48 小时的供体肾(HRUW 组)。
在早期,HRUW 溶液减少了肾移植中的氧化应激、管状细胞凋亡和间质巨噬细胞浸润。因此,与单纯使用 UW 溶液冷储存相比,HRUW 溶液改善了肾功能并延长了受体的存活率。组织病理学检查显示,HRUW 治疗减轻了管状损伤并抑制了间质纤维化的发展。
与单纯使用 UW 溶液冷储存相比,HRUW 溶液通过保护管状上皮细胞免受炎症和凋亡,改善了移植物的功能并延长了移植物的存活时间。我们的器官保存新方法是一种具有开创性的、安全的、简单的策略,可能在临床环境中得到应用。