Nakayama Masaaki, Zhu Wan-Jun, Watanabe Kimio, Gibo Ayano, Sherif Ali M, Kabayama Shigeru, Ito Sadayoshi
Tohoku University, Tohoku University Hospital, Research Division of Chronic Kidney Disease and Dialysis Treatment, 1-1 Seiryo-machi, Aoba-ku, Sendai city, 980-8574, Japan.
Tohoku University, United Centers for Advanced Research and Translational Medicine, Center for Advanced and Integrated Renal Science, Sendai, Japan.
BMC Nephrol. 2017 Oct 31;18(1):327. doi: 10.1186/s12882-017-0741-0.
Peritoneal dialysis (PD) is used as renal replacement therapy in patients with end-stage kidney disease. However, peritoneal membrane failure remains problematic and constitutes a critical cause of PD discontinuation. Recent studies have revealed the unique biological action of molecular hydrogen (H) as an anti-oxidant, which ameliorates tissue injury. In the present study, we aimed to examine the effects of H on the peritoneal membrane of experimental PD rats.
Eight-week-old male Sprague-Dawley rats were divided into the following groups (n = 8-11 each) receiving different test solutions: control group (no treatment), PD group (commercially available lactate-based neutral 2.5% glucose PD solution), and HPD group (PD solution with dissolved H at 400 ppb). Furthermore, the influence of iron (FeCl: 5 μM: inducer of oxidative cellular injury) in the respective PD solutions was also examined (Fe-PD and Fe-HPD groups). The HPD solution was manufactured by bathing a PD bag in H-oversaturated water created by electrolysis of the water. Twenty mL of the test solutions were intraperitoneally injected once a day for 10 days. Parietal peritoneum samples and cells collected from the peritoneal surface following treatment with trypsin were subjected to analysis.
In the PD group as compared to controls, a mild but significant sub-mesothelial thickening was observed, with increase in the number of cells in the peritoneal surface tissue that were positive for apoptosis, proliferation and vimentin, as seen by immunostaining. There were significantly fewer of such changes in the HPD group, in which there was a dominant presence of M2 (CD163+) macrophages in the peritoneum. The Fe-PD group showed a significant loss of mesothelial cells with sub-mesothelial thickening, these changes being ameliorated in the Fe-HPD group.
H-dissolved PD solutions could preserve mesothelial cells and peritoneal membrane integrity in PD rats. Clinical application of H in PD could be a novel strategy for protection of peritoneal tissue during PD treatment.
腹膜透析（PD）被用作终末期肾病患者的肾脏替代疗法。然而，腹膜衰竭仍然是个问题，并且是PD治疗中断的关键原因。最近的研究揭示了分子氢（H）作为一种抗氧化剂的独特生物学作用，它可以减轻组织损伤。在本研究中，我们旨在研究H对实验性PD大鼠腹膜的影响。
将8周龄雄性Sprague-Dawley大鼠分为以下几组（每组n = 8 - 11），给予不同的测试溶液：对照组（未治疗）、PD组（市售基于乳酸盐的中性2.5%葡萄糖PD溶液）和HPD组（溶解有400 ppb H的PD溶液）。此外，还研究了各PD溶液中铁（FeCl：5 μM：细胞氧化损伤诱导剂）的影响（Fe-PD组和Fe-HPD组）。HPD溶液是通过将PD袋浸泡在通过水电解产生的H过饱和水中制成的。每天腹腔注射20 mL测试溶液，持续10天。对用胰蛋白酶处理后从腹膜表面收集的壁层腹膜样本和细胞进行分析。
与对照组相比，PD组观察到轻度但显著的间皮下增厚，通过免疫染色可见腹膜表面组织中凋亡、增殖和波形蛋白阳性细胞数量增加。HPD组中此类变化明显较少，其中腹膜中主要存在M2（CD163 +）巨噬细胞。Fe-PD组显示间皮细胞显著丢失并伴有间皮下增厚，这些变化在Fe-HPD组中得到改善。
溶解有H的PD溶液可在PD大鼠中保留间皮细胞和腹膜完整性。H在PD中的临床应用可能是PD治疗期间保护腹膜组织的一种新策略。
