1] Department of Pharmacology, Graduate School of Medicine, Chiba University, Chiba [2] Division of Molecular Design, Medical Institute of Bioregulation, Kyushu University, Fukuoka [3] Research Center for Nucleotide Pool, Kyushu University, Fukuoka, Japan [4].
Sci Rep. 2013 Nov 20;3:3273. doi: 10.1038/srep03273.
The therapeutic potential of molecular hydrogen (H₂) is emerging in a number of human diseases and in their animal models, including in particular Parkinson's disease (PD). H₂ supplementation of drinking water has been shown to exert disease-modifying effects in PD patients and neuroprotective effects in experimental PD model mice. However, H₂ supplementation does not result in detectable changes in striatal H₂ levels, indicating an indirect effect. Here we show that H₂ supplementation increases gastric expression of mRNA encoding ghrelin, a growth hormone secretagogue, and ghrelin secretion, which are antagonized by the β1-adrenoceptor blocker, atenolol. Strikingly, the neuroprotective effect of H₂ water was abolished by either administration of the ghrelin receptor-antagonist, D-Lys(3) GHRP-6, or atenolol. Thus, the neuroprotective effect of H₂ in PD is mediated by enhanced production of ghrelin. Our findings point to potential, novel strategies for ameliorating pathophysiology in which a protective effect of H₂ supplementation has been demonstrated.
氢气（H₂）在许多人类疾病及其动物模型中具有治疗潜力，特别是帕金森病（PD）。研究表明，H₂ 饮用水补充剂可对 PD 患者发挥疾病修饰作用，并对实验性 PD 模型小鼠具有神经保护作用。然而，H₂ 补充剂并未导致纹状体 H₂ 水平发生可检测的变化，表明存在间接作用。在这里，我们发现 H₂ 补充剂可增加胃中生长激素释放肽（ghrelin）mRNA 的表达，ghrelin 是一种生长激素释放肽，而β1-肾上腺素受体阻滞剂阿替洛尔可拮抗其作用。引人注目的是，H₂ 水的神经保护作用被 ghrelin 受体拮抗剂 D-Lys（3）GHRP-6 或阿替洛尔的给药所消除。因此，H₂ 在 PD 中的神经保护作用是通过增强 ghrelin 的产生来介导的。我们的研究结果为改善已证明具有 H₂ 补充剂保护作用的病理生理学提供了潜在的新策略。
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