Nrf2抑制氧化应激对放射性组织纤维化的作用研究进展

Research progress of Nrf2 alleviating radiation-induced fibrosis by inhibiting oxidative stress

放射性组织纤维化是放射治疗的严重长期不良反应。研究表明,核因子E2相关因子2(nuclear factor-E2 related factor 2,Nrf2)通过增强内源性抗氧化防御机制,对放射性组织纤维化有一定减轻和预防作用。近年来的研究发现,放射性组织纤维化不仅与电离辐射诱导的直接DNA损伤有关,而且与组织中水分子产生的活性氧类物质(ROS)引起的间接损伤有关。Nrf2通过与抗氧化反应元件ARE结合以启动下游靶基因及相关抗氧化酶表达,中和放射产生的ROS,促进DNA修复以及抑制炎性因子的激活来减轻放射诱导的氧化应激和细胞凋亡及衰老,从而发挥了抗纤维化作用。诱导Nrf2对抗放射性损伤中的氧化应激有望成为降低随后的组织纤维化程度的一个很好策略。但能否安全运用于临床治疗,还需进一步的深入研究。文章综述Nrf2通过抑制氧化应激在放射性组织纤维化中的作用及研究进展,为放射治疗所致的组织纤维化预防以及患者放射治疗后的组织修复相关研究提供新思路。

Radiation-induced fibrosis(RIF)is a serious and long-term adverse effect in radiation therapy.Studies have shown that Nuclear factor-E2 related factor 2(Nrf2)can reduce and prevent RIF by up-regulations in endogenous antioxidant defenses.Recent studies have found that RIF is not only related to Ionizing radiation-induced direct DNA damage,but also to reactive oxygen species(ROS)-induced indirect damage via interacting with water molecules within cells.Nrf2 alleviates radiation-induced oxidative stress,apoptosis and senescence by binding to the antioxidant-responsive element(ARE)to initiate the expression of downstream target genes and related antioxidant enzymes,neutralize radiation-generated ROS,promote DNA repair,and inhibit the activation of inflammatory factors and aging,thereby exerting an anti-fibrotic effect.Nrf2 can be induced to combat oxidative stress of RFI during radiation damage,which is expected to be a good strategy to reduce the degree of subsequent tissue fibrosis.However,whether it can be safely applied in clinical treatment still needs further in-depth research.This article reviews the role and research progress of Nrf2 in RFI by inhibiting oxidative stress,and provides new ideas for the prevention of FRI and the related research on wound healing after radiotherapy.