谢建林, 林明宝, 侯琦. 核转录因子Nrf2与肺部炎症疾病研究进展J. 药学学报, 2015,50(9): 1080-1087.
引用本文: 谢建林, 林明宝, 侯琦. 核转录因子Nrf2与肺部炎症疾病研究进展J. 药学学报, 2015,50(9): 1080-1087.
XIE Jian-lin, LIN Ming-bao, HOU Qi. Recent advances in the study of Nrf2 and inflammatory respiratory diseasesJ. Acta Pharmaceutica Sinica, 2015,50(9): 1080-1087.
Citation: XIE Jian-lin, LIN Ming-bao, HOU Qi. Recent advances in the study of Nrf2 and inflammatory respiratory diseasesJ. Acta Pharmaceutica Sinica, 2015,50(9): 1080-1087.

核转录因子Nrf2与肺部炎症疾病研究进展

Recent advances in the study of Nrf2 and inflammatory respiratory diseases

  • 摘要: 核因子NF-E2相关因子(nuclear factor erythroid 2-related factor 2, Nrf2)是氧化应激反应敏感基因的重要转录因子之一,可调节依赖抗氧化反应元件(antioxidant response elements, ARE)的多种抗氧化蛋白的生成。研究显示, Nrf2-Keap1(Kelch样ECH联合蛋白1)-ARE信号通路是细胞内重要的内源性抗氧化防御机制之一,上调该信号通路可诱导其下游调控的多种抗氧化酶及解毒酶,提高谷胱甘肽及超氧化物歧化酶等抗氧化物质的表达水平,清除自由基,维持细胞内氧化还原平衡状态,发挥内源性细胞保护作用。近年来,大气污染尤其PM2.5可能是导致呼吸道炎症发病率升高以及炎症加重的关键因素之一, Nrf2及其信号通路对气道炎症性疾病如支气管哮喘、慢性阻塞性肺疾病(chronic obstructive pulmonary disease, COPD)和急性肺损伤(acute lung injury,ALI)的调控,有望成为防治肺部炎症性疾病药物研究潜在性靶点。本文就Nrf2与气道炎症和氧化应激相关信号通路调控进行综述。

     

    Abstract: Nuclear factor-erythroid 2 related factor 2 (Nrf2) is an ubiquitous and important transcription factor. It regulates antioxidant response elements (AREs)-mediated expression of antioxidant enzyme and cytoprotective proteins. A large body of research showed that Nrf2-Keap1 (Kelch-like ECH-associated protein1, Keap1)-ARE signaling pathway is involved in the endogenous antioxidant defense mechanisms. Nrf2 increases the expression of a number of cytoprotective genes, protects cells and tissues from the injury of a variety of toxicants and carcinogens. As a result, Nrf2 enhances the expression of glutathione and antioxidants such as superoxide dismutase and glutathione S-transferase, and subsequently scavenging free radicals. Air pollution especially from PM2.5 particles, is associated with an increasing morbidity of inflammatory pulmonary diseases and their deterioration. More and more studies demonstrated that Nrf2 was a novel signaling molecule in the modulation of inflammatory responses in these inflammatory respiratory diseases, such as asthma, acute lung injury (ALI) and COPD. Therefore, Nrf2 targeting might be a therapeutic target, which will provide clinical benefit by reducing both oxidative stress and inflammation in asthma, acute lung injury (ALI) and COPD. This review focused on the relationship between Nrf2 and inflammatory respiratory diseases and oxidative stress.

     

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