摘要
核因子E2相关因子2(nuclear factor erythroid 2-related factor 2,Nrf2)是应对氧化应激的敏感因子,通过调控体内的抗氧化酶和解毒酶,降低有毒物质对机体的损伤。核因子κB(nuclear factor-kappa light chain enhancer of B cells,NF-κB)是调节炎症反应和免疫应答的关键因子。生理条件下,两个转录因子相互制约共同维持细胞内氧化还原平衡。功能水平分析Nrf2缺失小鼠,NF-κB的诱导明显增强,相反地,NF-κB也可抑制Nrf2的活性。研究表明,药源性肝损伤(drug induced liver injury,DILI)的分子机制是扰乱了Nrf2和NF-κB通路之间的平衡。近年来,发现许多天然活性物质同时具有激活Nrf2和抑制NF-κB的药理效应。因此,这两条通路中的交互环节有望成为治疗和预防DILI的靶点。笔者旨在阐述Nrf2和NF-κB在DILI中交互的分子机制以及探究天然药理活性物质如何调节Nrf2和NF-κB通路。
Nrf2 （ nuclear factor erythroid 2-related factor 2）, a transcription factor, is sensitive to oxidative stress. It drives the pro- duction of endogenous antioxidant enzymes and detoxifying enzymes to prevent damage from poisonous substance. NF-κB （ nuclear fac- tor-kappa light chain enhancer of B cells） is an essential transcription factor for regulation of immuno-inflammatory reaction. The two pathways interact to maintain intracellular redox homeostasis under physiological conditions. Nrf2 deficient mice exhibit greater induc- tion of NF-KB, whereas NF-κB also inhibit Nrf2 activity at function level. Previous studies indicate the molecular mechanism of drug induced liver injury （DILI） is the imbalance of Nrf2 and NF-κB pathways. Recently, many bioactive natural products could active Nrf2 and inhibit NF-κB. Hence, the interaction of the two pathways may be targets for the treatment and prevention of DILl. The aims of this review are to dissect the interactive molecular mechanism between Nrf2 and NF-κB in DILI, and explore how natural pharmaco- logical active products regulate Nrf2 and NF-κB pathways.
作者
李紫薇
黄菁菁
杨婉花
LI Zi-wei, HUANG Jing-jing, YANG Wan-hua(Department of Pharmacy, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, Chin)
出处
《中国药学杂志》
CAS
CSCD
北大核心
2018年第9期666-670,共5页
Chinese Pharmaceutical Journal
基金
国家自然科学基金青年项目资助(81503137)
关键词
药源性肝损伤
核因子E2相关因子2
核因子-ΚB
氧化应激
炎症反应
drug induced liver injury
nuclear factor erythroid 2-related factor 2
NF-κB
oxidative stress
inflammatory reaction
