Oral Administration of Si-Based Agent Attenuates Oxidative Stress and Ischemia-Reperfusion Injury in a Rat Model: A Novel Hydrogen Administration Method
Oral Administration of Si-Based Agent Attenuates Oxidative Stress and Ischemia-Reperfusion Injury in a Rat Model: A Novel Hydrogen Administration Method
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DOI：
10.3389/fmed.2020.00095
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发表时间：
2020-03-20
影响因子：
3.9
通讯作者：
Nonomura, Norio
中科院分区：
文献类型：
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作者：
Kawamura, Masataka;Imamura, Ryoichi;Nonomura, Norio
器官缺血再灌注损伤(IRI)是肾移植过程中不可避免的一种损伤，它会导致体内活性氧物质的产生，从而导致器官损伤。尽管分子氢(H-2)治疗IRI的疗效已有报道，但口服富含H-2的水和吸入H-2气体仍然没有在临床上广泛使用，因为缺乏效率和操作困难。我们成功地将硅(Si)粉碎成纳米硅颗粒(Nano-Si)，并允许其与水反应，从而生成了大量的H-2分子。将纳米硅或相对大尺寸的硅颗粒(大硅)灌胃给肾缺血再灌注大鼠。动物分为假手术组、缺血再灌注组、再灌注+纳米硅组和再灌注+大硅组。给予纳米硅的大鼠IRI后72h，血肌酐和尿蛋白水平显著降低。氧化应激标志物8-羟基脱氧鸟苷水平也显著降低。转录组和基因本体论分析表明，口服纳米硅的摄入下调了与氧化应激相关的生物学过程，如免疫反应、细胞因子的产生和外源性的凋亡信号通路。定量聚合酶链式反应验证了改变途径中基因子集调控的改变。此外，免疫组织化学分析显示，纳米硅处理减轻了间质巨噬细胞的浸润和肾小管上皮细胞的凋亡，提示纳米硅具有抗炎和抗细胞凋亡的作用。结论：口服纳米硅可减轻肾脏IRI，是一种新的H-2给药方法。
Organ ischemia-reperfusion injury (IRI), which is unavoidable in kidney transplantation, induces the formation of reactive oxygen species and causes organ damage. Although the efficacy of molecular hydrogen (H-2) in IRI has been reported, oral intake of H-2-rich water and inhalation of H-2 gas are still not widely used in clinical settings because of the lack of efficiency and difficulty in handling. We successfully generated large quantities of H-2 molecules by crushing silicon (Si) to nano-sized Si particles (nano-Si) which were allowed to react with water. The nano-Si or relatively large-sized Si particles (large-Si) were orally administered to rats with renal IRI. Animals were divided into four groups: sham, IRI, IRI + nano-Si, and IRI + large-Si. The levels of serum creatinine and urine protein were significantly decreased 72 h following IRI in rats that were administered nano-Si. The levels of oxidative stress marker, urinary 8-hydroxydeoxyguanosine were also significantly decreased with the nano-Si treatment. Transcriptome and gene ontology enrichment analyses showed that the oral nano-Si intake downregulated the biological processes related to oxidative stress, such as immune response, cytokine production, and extrinsic apoptotic signaling pathway. Alterations in the regulation of a subset of genes in the altered pathways were validated by quantitative polymerase chain reaction. Furthermore, immunohistochemical analysis demonstrated that the nano-Si treatment alleviated interstitial macrophage infiltration and tubular apoptosis, implicating the anti-inflammatory and anti-apoptotic effects of nano-Si. In conclusion, renal IRI was attenuated by the oral administration of nano-Si, which should be considered as a novel H-2 administration method.