Hydrogen-rich pure water prevents cigarette smoke-induced pulmonary emphysema in SMP30 knockout mice
Hydrogen-rich pure water prevents cigarette smoke-induced pulmonary emphysema in SMP30 knockout mice
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DOI：
10.1016/j.bbrc.2017.08.035
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发表时间：
2017-10-07
影响因子：
3.1
通讯作者：
Takahashi, Kazuhisa
中科院分区：
文献类型：
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作者：
Suzuki, Yohei;Sato, Tadashi;Takahashi, Kazuhisa
慢性阻塞性肺疾病（COPD）主要是一种由香烟烟雾（CS）引发的疾病，具有慢性全身性炎症的特征。CS产生的氧化剂可导致呼吸系统DNA损伤和应激诱导的细胞过早衰老，在COPD中发挥重要作用。因此，抗氧化剂应该为COPD的治疗提供益处;然而，由于这种疾病的复杂性，它们的治疗潜力仍然有限。最近，分子氢（H-2）已被报道作为一种预防性和治疗性抗氧化剂。分子H-2可以选择性地减少羟基自由基的积累，没有已知的副作用，在管理氧化应激，炎症，细胞凋亡和脂质代谢中显示出潜在的应用。然而，尚未有关于分子H-2在COPD患者中的疗效的报道。在本研究中，我们使用了小鼠模型的慢性阻塞性肺病，以调查是否CS诱导的肺组织损伤可以通过管理分子H-2衰减。我们给衰老标记蛋白30敲除（SMP 3 O-KO）小鼠施用富含H-2的纯水，使其暴露于CS 8周。给予富含H-2的水减轻了CS诱导的SMP 3 O-KO小鼠的肺损伤，并降低了肺的平均线性截距和破坏指数。此外，与CS暴露的H-2未处理的小鼠相比，富含H-2的水显著恢复CS暴露的小鼠的静态肺顺应性。此外，用富含H-2的水处理降低了CS暴露小鼠中氧化DNA损伤标记物（如磷酸化组蛋白H2 AX和8-羟基-2 '-脱氧鸟苷）和衰老标记物（如细胞周期蛋白依赖性激酶抑制剂2A、细胞周期蛋白依赖性激酶抑制剂1和β-半乳糖苷酶）的水平。这些结果表明，富含H-2的纯水通过减少CS诱导的肺中的氧化性DNA损伤和过早细胞衰老来减轻SMP 3 O-KO小鼠中CS诱导的肺气肿。我们的研究表明，分子H-2的管理可能是一种新的预防和治疗COPD的策略。(C)2017爱思唯尔公司All rights reserved.
Chronic obstructive pulmonary disease (COPD) is predominantly a cigarette smoke (CS)-triggered disease with features of chronic systemic inflammation. Oxidants derived from CS can induce DNA damage and stress-induced premature cellular senescence in the respiratory system, which play significant roles in COPD. Therefore, antioxidants should provide benefits for the treatment of COPD; however, their therapeutic potential remains limited owing to the complexity of this disease. Recently, molecular hydrogen (H-2) has been reported as a preventive and therapeutic antioxidant. Molecular H-2 can selectively reduce hydroxyl radical accumulation with no known side effects, showing potential applications in managing oxidative stress, inflammation, apoptosis, and lipid metabolism. However, there have been no reports on the efficacy of molecular H-2 in COPD patients. In the present study, we used a mouse model of COPD to investigate whether CS-induced histological damage in the lungs could be attenuated by administration of molecular H-2. We administered H-2-rich pure water to senescence marker protein 30 knockout (SMP3O-KO) mice exposed to CS for 8 weeks. Administration of H-2-rich water attenuated the CS-induced lung damage in the SMP3O-KO mice and reduced the mean linear intercept and destructive index of the lungs. Moreover, H-2-rich water significantly restored the static lung compliance in the CS-exposed mice compared with that in the CS-exposed H-2-untreated mice. Moreover, treatment with H-2-rich water decreased the levels of oxidative DNA damage markers such as phosphorylated histone H2AX and 8-hydroxy-2'-deoxyguanosine, and senescence markers such as cyclin-dependent kinase inhibitor 2A, cyclin-dependent kinase inhibitor 1, and P-galactosidase in the CS-exposed mice. These results demonstrated that H-2-rich pure water attenuated CS-induced emphysema in SMP3O-KO mice by reducing CS-induced oxidative DNA damage and premature cell senescence in the lungs. Our study suggests that administration of molecular H-2 may be a novel preventive and therapeutic strategy for COPD. (C) 2017 Elsevier Inc. All rights reserved.