Nrf2/ARE信号通路在抑郁症中的研究进展  

Advances of Nrf 2/ARE Signaling Pathway in the Major Depression Disorder

作　　者：王莎莎 张钊[2] 张美金[2] 胡金凤[2] 陈乃宏 WANG Sha-sha;ZHANG Zhao;ZHANG Mei-jin;HU Jin-feng;CHEN Nai-hong(College of Traditional Chinese Medicine,Shanxi University of Chinese Medcine,Shanxi,030619,China;State Key Laboratory of Bioactive Substances and Functions of Natural Medicines,Institute of Materia Medica, Neuroscienee Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, China)

机构地区：[1]山西中医药大学,中药学院,中国太原030619 [2]天然药物活性物质与功能国家重点实验室,中国医学科学院北京协和医学院药物研究所,中国北京100050

出　　处：《神经药理学报》2016年第3期32-37,共6页Acta Neuropharmacologica

基　　金：国家自然科学基金项目(No.81274122、81373997、81273629、81473376、U1402221、81573640);北京市自然科学基金项目(No.7131013);新药作用机制研究与药效评价北京市重点实验室资助项目(No.BZ0150)

摘　　要：抑郁症是严重危害人类身心健康的重要疾病,氧化应激与慢性炎症反应是其发病的主要作用机制之一。由于心理应激导致的交感神经过度激活以及下丘脑-垂体-肾上腺(hypothalamic-pituitary-adrenal,HPA)轴过度兴奋引起的糖皮质激素水平升高,都可引发氧化应激与炎症反应。核因子E2相关因子2(nuclear factor erythroid-2-related factor 2,Nrf2)/抗氧化反应元件(anti-oxidant response element,ARE)信号通路是体内主要的抗氧化信号途径,Nrf2作为转录因子,可通过与ARE的结合对机体主要的抗氧化酶表达发挥调控作用。前期研究表明Nrf2-/-小鼠具有典型的抑郁症状表现,而给予抗炎药物治疗后可显著缓解其抑郁症状,提示免疫炎症在Nrf2缺失引发的抑郁症中具有重要的作用。该文将对抑郁症中Nrf2介导的抗氧化应激和调控免疫炎症的作用机制进行综述,以期为Nrf2/ARE信号通路为靶标,开发新型的抗抑郁药物奠定理论基础。Major depression disorder is a seriously psychological disease, which was characterized by oxidative stress and inflammation in pathogenesis. Oxidative stress and inflammatory response can be induced by excessive activation of thesympathetic nerve and hypothalamic pituitary adrenal axis,which would increase the level of glucocorticoid significantly in depression individuals. Nrf2/ARE signaling pathway is the main antioxidant signaling pathway,Nrf2 as a transcription factor, can be combined with ARE in the nuclear and induce antioxidant enzymes expression. Previous studies showed that Nrf2-/- mice with typical symptoms of depression, while treated with anti-inflammatory drugs alleviate it significantly, suggesting that the immune inflammatory was involved in depression caused by Nrf2 deletion. This article will review the role of Nrf2 mediated oxidative stress and immune inflammation in depression, and provided the theoretical basis for Nrf2/ARE signaling pathway as a novel target for antidepressant development.

关 键 词：抑郁症 NRF2 氧化应激 炎症 抗氧化剂 

分 类 号：R964[医药卫生—药理学]