Nrf2/ARE信号通路激活对放射治疗中减轻组织损伤的作用机制  

Activation of Nrf2/ARE signal pathway reduces radiotherapy-induced tissue injury

作　　者：林培琦 龙远铸 张霓霓 黄桂林 Lin Peiqi;Long Yuanzhu;Zhang Nini;Huang Guilin(Zunyi Medical University,Zunyi 563000,Guizhou Province,China;Department of Maxillofacial Surgery,Affiliated Stomatological Hospital of Zunyi Medical University,Zunyi 563000,Guizhou Province,China)

机构地区：[1]遵义医科大学,贵州省遵义市563000 [2]遵义医科大学附属口腔医院颌面外科,贵州省遵义市563000

出　　处：《中国组织工程研究》2022年第11期1780-1787,共8页Chinese Journal of Tissue Engineering Research

基　　金：国家自然科学基金(81960204),项目负责人:黄桂林;国家自然科学基金(81860198),项目负责人:张霓霓。

摘　　要：背景:放射治疗的严重并发症之一是放射性电离辐射所致的组织损伤。研究表明,通过Nrf2/ARE信号通路激活内源性抗氧化应激反应,对放射性组织损伤有一定的预防与治疗作用。目的:阐释Nrf2/ARE信号通路激活对放射性组织损伤的预防与修复的作用,为探索预防放射治疗并发症策略的新思路。方法:计算机检索PubMed、Web of Science、中国知网、万方数据和维普数据库相关文献,以"放射性损伤,辐射损伤,放射损伤,放射性组织损伤(肠、肝、舌、肺、骨髓、皮肤、造血系统、神经系统及循环系统等),辐射综合征,Nrf2"为中文数据库检索词,以"radiation injury,radiation-induced tissue injury,radiation damage,radiation syndrome,Nrf2"为英文数据库检索词,最终纳入67篇文献进行综述。结果与结论:(1)放射性组织损伤是由于电离辐射生物分子的分子内键均裂,导致细胞毒性自由基与活性氧增加,从而引起相关组织损伤。(2)Nrf2/ARE信号通路是重要的机体内源性抗氧化防御机制,通过增强抗氧化反应元件表达,达到减轻DNA损伤、促进受损DNA修复和抑制放射诱导细胞凋亡的目的,因此Nrf2/ARE信号通路对参与预防与纠正包括放射性组织损伤在内的细胞氧化还原失衡有重要意义。(3)目前研究发现,Nrf2/ARE信号通路的激活存在两面性,一方面通过Nrf2/ARE信号通路激活剂的运用,不仅能够预防放射治疗所致组织损失,还能诱导放射后受损组织修复;另一方面,各种原因所致的Nrf2/ARE信号通路长期和慢性激活,存在恶性肿瘤对放、化疗的敏感性降低的风险。(4)上述文献证据表明,Nrf2/ARE信号通路具有作为放射治疗并发症的新防治策略潜力,但是否能广泛运用于临床,还需更加深入的研究来证实。BACKGROUND:Tissue damage induced by radioactive ionizing radiation is one of the serious complications of radiotherapy.Activation of endogenous antioxidative stress response through nuclear factor(erythroid-derived 2)-like 2(Nrf2)/antioxidant responsive element(ARE)signaling pathway has shown preventive and therapeutic effects on radiation-induced tissue injuries.OBJECTIVE:To explain the preventive and therapeutic mechanisms of Nrf2/ARE signaling pathway on radiation-induced injuries,and provide new ideas for exploring the treatment and prevention strategies of radiotherapy complications.METHODS:PubMed,Web of Science,CNKI,WanFang and VIP databases were searched using the keywords of"radiation injury,radiation-induced tissue injury(intestine,liver,tongue,lung,bone marrow,skin,hematopoietic system,nervous system,circulatory system),radiation damage,radiation syndrome,Nrf2"in Chinese and English,respectively.A total of 67 literatures were finally included and reviewed.RESULTS AND CONCLUSION:Radiation-induced injury is damage to tissues caused by the intramolecular bond homolysis of ionizing radiation biomolecules that lead to an increase in cytotoxic free radicals and reactive oxygen species.The Nrf2/ARE signaling pathway is an important endogenous antioxidant defense mechanism in the body.By enhancing the expression of antioxidant response elements,it can reduce DNA damage,promote damaged DNA repair,and inhibit radiation-induced cell apoptosis.Therefore,the Nrf2/ARE signaling pathway is of great significance for the prevention and correction of cellular redox imbalances including radioactive tissue damage.Current studies have found that the activation of Nrf2/ARE signaling pathway has two sides.On the one hand,the application of Nrf2/ARE signaling pathway activator cannot only prevent tissue loss caused by radiotherapy,but also induce the repair of damaged tissue after radiotherapy.On the other hand,the long-term and chronic activation of the Nrf2/ARE signaling pathway caused by various reasons may reduce the sensi

关 键 词：放射性组织损伤 放射治疗 电离辐射 辐射损伤 抗氧化应激 NRF2 ARE 修复与再生 

分 类 号：R459.9[医药卫生—治疗学] R363[医药卫生—临床医学]