Abstract：
Oxidative stress plays a key role in chronic kidney disease (CKD) development and progression, inducing kidney cell damage, inflammation, and fibrosis. However, effective therapeutic interventions to slow down CKD advancement are currently lacking. The multifaceted pharmacological effects of molecular hydrogen (H2) have made it a promising therapeutic avenue. H2 is capable of capturing harmful •OH and ONOO- while maintaining the crucial reactive oxygen species (ROS) involved in cellular signaling. The NRF2-KEAP1 system, which manages cell redox balance, could be used to treat CKD. H2 activates this pathway, fortifying antioxidant defenses and scavenging ROS to counteract oxidative stress. H2 can improve NRF2 signaling by using the Wnt/β-catenin pathway and indirectly activate NRF2-KEAP1 in mitochondria. Additionally, H2 modulates NF-κB activity by regulating cellular redox status, inhibiting MAPK pathways, and maintaining Trx levels. Treatment with H2 also attenuates HIF signaling by neutralizing ROS while indirectly bolstering HIF-1α function. Furthermore, H2 affects FOXO factors and enhances the activity of antioxidant enzymes. Despite the encouraging results of bench studies, clinical trials are still limited and require further investigation. The focus of this review is on hydrogen\'s role in treating renal diseases, with a specific focus on oxidative stress and redox signaling regulation, and it discusses its potential clinical applications.
摘要：
氧化应激在慢性肾脏病(CKD)的发生、发展中起着关键作用,诱导肾细胞损伤，炎症,和纤维化。然而,目前缺乏减缓CKD进展的有效治疗干预措施.分子氢（H2）的多方面药理作用使其成为有希望的治疗途径。H2能够捕获有害的·OH和ONOO-，同时维持参与细胞信号传导的关键活性氧（ROS）。NRF2-KEAP1系统，管理细胞氧化还原平衡，可用于治疗CKD。H2激活了这个途径,强化抗氧化防御和清除ROS以抵消氧化应激。H2可以通过Wnt/β-catenin途径改善NRF2信号传导，并间接激活线粒体中的NRF2-KEAP1。此外,H2通过调节细胞氧化还原状态调节NF-κB活性，抑制MAPK通路，并保持Trx水平。用H2处理还通过中和ROS减弱HIF信号,同时间接增强HIF-1α功能。此外，H2影响FOXO因子并增强抗氧化酶的活性。尽管实验室研究的结果令人鼓舞，临床试验仍然有限,需要进一步研究.这篇综述的重点是氢在治疗肾脏疾病中的作用，特别关注氧化应激和氧化还原信号调节，并讨论了其潜在的临床应用。
