Department of Surgery, University of Pittsburgh Medical Center, 200 Lothrop Street, Pittsburgh, Pennsylvania 15213, USA.
Kidney Int. 2010 Jan;77(2):101-9. doi: 10.1038/ki.2009.421. Epub 2009 Nov 11.
Reactive oxygen species (ROS) contribute to the development of interstitial fibrosis and tubular atrophy seen in chronic allograft nephropathy (CAN). As molecular hydrogen gas can act as a scavenger of ROS, we tested the effect of treatment with hydrogen water (HW) in a model of kidney transplantation, in which allografts from Lewis rats were orthotopically transplanted into Brown Norway recipients that had undergone bilateral nephrectomy. Molecular hydrogen was dissolved in water and recipients were given HW from day 0 until day 150. Rats that were treated with regular water (RW) gradually developed proteinuria and their creatinine clearance declined, ultimately leading to graft failure secondary to CAN. In contrast, treatment with HW improved allograft function, slowed the progression of CAN, reduced oxidant injury and inflammatory mediator production, and improved overall survival. Inflammatory signaling pathways, such as mitogen-activated protein kinases, were less activated in renal allografts from HW-treated rats as compared with RW-treated rats. Hence, oral HW is an effective antioxidant and antiinflammatory agent that prevented CAN, improved survival of rat renal allografts, and may be of therapeutic value in the setting of transplantation.
活性氧 (ROS) 有助于慢性移植肾肾病 (CAN) 中观察到的间质纤维化和肾小管萎缩的发展。由于氢气可以作为 ROS 的清除剂，我们在肾移植模型中测试了氢水 (HW) 治疗的效果，在该模型中，来自 Lewis 大鼠的同种异体移植物被原位移植到接受过双侧肾切除术的 Brown Norway 受者体内。氢气溶解在水中，受者从第 0 天到第 150 天给予 HW。用常水 (RW) 治疗的大鼠逐渐出现蛋白尿，其肌酐清除率下降，最终导致 CAN 继发的移植物失功。相比之下，HW 治疗改善了同种异体移植物功能，减缓了 CAN 的进展，减少了氧化损伤和炎症介质的产生，并提高了整体存活率。HW 治疗的大鼠肾同种异体移植物中的促分裂原激活蛋白激酶等炎症信号通路的激活程度低于 RW 治疗的大鼠。因此，口服 HW 是一种有效的抗氧化和抗炎剂，可预防 CAN，改善大鼠肾移植的存活率，并可能在移植中具有治疗价值。
