Nrf2:非酒精性脂肪性肝病的新靶点  

Nrf2:a new target for nonalcoholic fatty liver disease

作　　者：陈智伟 孙华 CHEN Zhi-wei;SUN Hua(State Key Laboratory of Bioactive Substance and Function of Natural Medicines,Institute of Materia Medica,Chinese Academy of Medical Sciences&Peking Union Medical College,Beijing 100050,China)

机构地区：[1]中国医学科学院、北京协和医学院药物研究所,天然药物活性物质与功能国家重点实验室,北京100050

出　　处：《药学学报》2022年第11期3268-3275,共8页Acta Pharmaceutica Sinica

基　　金：国家科技重大专项重大新药创制项目(2019ZX09201001-002-004);国家重点研发计划-中医药现代化项目(2019YFC1708901);中国医学科学院医学与健康科技创新工程项目(2021-I2M-1-028)。

摘　　要：肝脏是机体重要器官,具有代谢、解毒等多种功能。由于生活方式的急剧改变和公共卫生水平的提高,非感染性疾病发病率显著上升,从根本上改变了世界大多数地区的疾病特点。目前,全球非酒精性脂肪性肝病(nonalcoholic fatty liver disease,NAFLD)的患病率大约为25%,约59.10%的NAFLD患者在5年内进展为非酒精性脂肪性肝炎(non-alcoholic steatohepatitis,NASH),约41%的NASH患者进展为纤维化。NAFLD已成为全球最主要的肝脏疾病之一,并可能在未来几十年内成为终末期肝病的主要原因。NAFLD和相关肝硬化会给患者、医疗保健系统和社会带来巨大经济负担。由于目前尚无获得美国食品和药品管理局(Food and Drug Administration,FDA)批准治疗的药物,NAFLD的治疗主要仍依靠运动和饮食等生活方式的改变。氧化应激和炎症是肝脏疾病发生和发展过程中最重要的病理过程。核因子E2相关因子2(nuclear factor erythroid-2-related factor 2,Nrf2)是机体抗氧化应激系统的关键调节因子,具有抗炎、抗氧化等多种功能。多项研究表明Nrf2通路显著影响NAFLD的进展。本综述旨在总结Kelch样ECH-关联蛋白1-Nrf2-抗氧化反应元件(Keap1-Nrf2-ARE)信号通路在NAFLD发病机制中的调节作用,并揭示Nrf2作为NAFLD治疗靶点的潜力。The liver is an important organ of the body,which has many functions,such as metabolism and detoxification.Due to the rapid change of lifestyle and the improvement of public health,the incidence rate of non-communicable diseases has increased significantly,which fundamentally changed the disease characteristics in most parts of the world.At present,the global prevalence of non-alcoholic fatty liver disease(NAFLD)is about25%.Moreover,about 59.10%of NAFLD patients progress to non-alcoholic steatohepatitis(NASH)within 5years,and about 41%of NASH patients progress to fibrosis.NAFLD has become one of the most important liver diseases in the world and may become the main cause of end-stage liver disease in the next few decades.In addition,NAFLD and related cirrhosis will bring huge economic burden to patients,health care system and society.Since there are currently no medications available that have been approved by Food and Drug Administration(FDA),NAFLD is still treated mainly through lifestyle changes such as exercise and diet.Oxidative stress and inflammation are the most important pathological processes in the occurrence and development of liver diseases.Nuclear factor erythroid-2-related factor 2(Nrf2)is a key regulator of the body’s antioxidant stress system,with anti-inflammatory,antioxidant and other functions.Many studies have shown that Nrf2 pathway significantly affects the progression of liver diseases.In this review,we aimed to summarize the regulatory role of the Kelch-like ECH-associating protein 1(Keap1)-Nrf2-antioxidant response element(ARE)signaling pathway in the pathogenesis of NAFLD,and to reveal the potential of Nrf2 as a therapeutic target for NAFLD.

关 键 词：核因子E2相关因子2 非酒精性脂肪性肝病 胰岛素抵抗 氧化应激 药物开发 

分 类 号：R966[医药卫生—药理学]