Nrf2对锰致GSH合成障碍的调控作用

Regulatory role of Nrf2 in manganese-induced GSH synthesis dysfunction

锰(manganese,Mn)是一种常见的环境和职业污染物,其主要的毒作用部位是脑。锰神经毒性的主要病变部位位于黑质、纹状体、苍白球和尾状核等,主要表现为锥体外系神经受损。其主要机制之一是由于体内氧化-抗氧化系统的失衡,产生大量的ROS(reactive oxygen species,ROS)引起氧化损伤。谷胱甘肽(glutathione,GSH)是体内重要的抗氧化物质,锰中毒时可以导致GSH合成障碍。核转录因子NF-E2相关因子2(nuclear factor-erythroid 2related factor 2,Nrf2)是一类具有抗氧化特征的转录因子,具有提高内源性GSH水平的作用。本文拟从锰暴露途径和神经毒性、锰与氧化应激、锰中毒对GSH的影响、Nrf2信号通路对锰致GSH合成障碍的调控四个方面作以综述。

Manganese （Mn） is a widespread environmental and occupational pollutant, and its target organ is the brain. Mn ac- cumulates in the substantia nigar, striatum, globus pallidus and caudate nucleus, and causes nerve injury in extrapyramidal sys- tem. One of the mechanisms on manganism is something that breaks the balance of oxidation- antioxidation system and results in over production of reactive oxygen species （ROS） and oxidative damage. Glutathione （GSH） is an important endogenous antioxi- dant. Mangansim can cause GSH synthesis dysfunction. Nuclear factor- frythroid 2 related factor 2 （Nrf2） is a transcription fac- tor with antioxidation characteristics, which increases the synthesis of endogenous GSH levels. This review will focus on four as- pects, including exposure pathway and neurotoxicity of Mn, Mn and oxidative stress, the effect of manganism on GSH and the regulatory role of Nrf2 in Mn induced GSH synthesis dysfunction.