Oxidative stress is proven to be critical for the initiation and progression of vitiligo. Molecular hydrogen (H₂) possesses potent antioxidant activity and has been shown to protect against various oxidative stress–related diseases. In this study, we first investigated the effects and mechanisms of H₂ in human melanocytes damaged by hydrogen peroxide. We initially found that H₂ reduced intracellular ROS accumulation and malondialdehyde levels in both vitiligo specimens and hydrogen peroxide–treated melanocytes in vitro in a concentration- and time-dependent manner, concomitant with the enhancement of antioxidant enzyme activity. Correspondingly, H₂ reversed hydrogen peroxide–induced apoptosis and dysfunction in both normal and vitiligo melanocytes. H₂ protected mitochondrial morphology and function in melanocytes under stress and promoted the activation of Nrf2 signaling, whereas Nrf2 deficiency abolished the protective effect of H₂ against hydrogen peroxide–induced oxidative damage. Furthermore, H₂ positively modulated β-catenin in hydrogen peroxide–treated melanocytes, and the β-catenin pathway was implicated in H₂-induced Nrf2 activation. Collectively, our results indicate that H₂ could be a promising therapeutic agent for vitiligo treatment via attenuating oxidative damage, and its beneficial effect in human melanocytes might involve Wnt/β-catenin–mediated activation of Nrf2 signaling.

氧化应激被证明对于白癜风的发生和发展至关重要。分子氢（H ₂）具有强大的抗氧化活性，并已被证明可以抵抗各种与氧化应激有关的疾病。在这项研究中，我们首先研究了H ₂在被过氧化氢损伤的人黑素细胞中的作用和机制。我们最初发现，H ₂以浓度和时间依赖性方式减少了体外白癜风标本和过氧化氢处理的黑素细胞中细胞内ROS的积累和丙二醛水平，同时还增强了抗氧化酶的活性。相应地，H ₂逆转过氧化氢引起的正常和白癜风黑素细胞的凋亡和功能障碍。H ₂保护了黑素细胞在压力下的线粒体形态和功能，并促进了Nrf2信号的激活，而Nrf2缺乏则取消了H ₂对过氧化氢引起的氧化损伤的保护作用。此外，H ₂在过氧化氢处理的黑素细胞中正调节β-catenin，而β-catenin途径与H ₂诱导的Nrf2活化有关。总的来说，我们的结果表明H ₂ 通过减轻氧化损伤，可能是治疗白癜风的有前途的治疗剂，其对人黑素细胞的有益作用可能涉及Wnt /β-catenin介导的Nrf2信号传导的激活。