抗氧化因子Nrf2对H_(2)O_(2)诱导的人黑素细胞氧化应激水平和抗氧化基因表达的影响  

The Role of Nrf2 in Modulating H_(2)O_(2)-induced Oxidative Stress and Nrf2 Target Antioxidant Gene Expression in Human Melanocytes

作　　者：王琪[1] 倪清蓉 姜兆婷 张甲 周钰奇 王博[1] 陈佳希[1] 易秀莉[1] 坚哲[1] WANG Qi;NI Qingrong;JIANG Zhaoting;ZHANG Jia;ZHOU Yuqi;WANG Bo;CHEN Jiaxi;YI Xiuli;JIAN Zhe(Department of Dermatology,Xijing Hospital,Fourth Military Medical University,Xi′an 710032,China)

机构地区：[1]第四军医大学西京皮肤医院,陕西西安710032

出　　处：《中国皮肤性病学杂志》2022年第7期744-750,共7页The Chinese Journal of Dermatovenereology

基　　金：国家自然科学基金(82173414,81872521);空军军医大学凌云工程翱翔计划(axjhjz-102)。

摘　　要：干预人黑素细胞中激活转录因子NF-E2相关因子2(Nrf2)的表达,观察其对过氧化氢(H_(2)O_(2))诱导的氧化损伤作用,以及对Nrf2下游相关抗氧化基因表达影响。方法将siRNA或pCMV6-XL5-Nrf2瞬时转染入PIG1细胞,从而上调或者下调Nrf2的表达,检测黑素细胞内活性氧簇(ROS)和丙二醛(MDA)浓度、细胞增殖情况,以及下游抗氧化基因还原型烟酰胺腺嘌呤二核苷酸磷酸[NAD(P)H]、醌氧化还原酶(NQO-1)、血红素氧化酶(HO-1)和谷氨酰半胱氨酸合成酶(γ-GCS)的表达。结果H_(2)O_(2)预处理可促进PIG1细胞中ROS和MDA的生成。上调Nrf2的表达可在人黑素细胞中抑制H_(2)O_(2)诱导的ROS和MDA产生,促进细胞增殖及Nrf2核转位,增强NQO-1、HO-1及γ-GCS的表达,而下调Nrf2表达可观察到相反的结果。结论在人黑素细胞中干预抗氧化因子Nrf2的表达可通过影响Nrf2相关抗氧化酶的活性来调控H_(2)O_(2)诱导的黑素氧化损伤及细胞增殖。Objective To investigate the effect of modulation of the nuclear factor E2-related factor 2(Nrf2)expression on H_(2)O_(2)-induced oxidative damage and Nrf2 target antioxidant gene expression in human melanocytes.Methods PIG1 cells were transiently transfected with Nrf2-specic siRNA or pCMV6-XL5-Nrf2 to downregulate or upregulate Nrf2 expression.H_(2)O_(2)-induced intracellular reactive oxygen species(ROS),malondialdehyde(MDA)and cell proliferation were detected.The levels of nicotinamide adenine dinucleotide phosphate[NAD(P)H],quinone oxidoreductase(NQO-1),heme oxygenase-1(HO-1),γ-glutamylcysteine synthetase(γ-GCS)and Nrf2 nuclear expression were determined.Results It was found that H_(2)O_(2) induced the expression of ROS and MDA in PIG1 cells.The upregulation of Nrf2 reduced the expression of H_(2)O_(2)-induced ROS and MDA,promoted cell proliferation,enhanced Nrf2 nuclear accumulation and upregulated the expression of NQO-1,HO-1 andγ-GCS in human melanocytes.However,the opposite result could be observed by down-regulating of Nrf2.Conclusion The modulation of Nrf2 alters H_(2)O_(2)-induced oxidative stress and cell proliferation though regulating the expression of Nrf2-mediated antioxidant enzymes in human melanocytes.

关 键 词：转录因子NF-E2相关因子2(Nrf2) 氧化应激 活性氧簇(ROS) 黑素细胞 白癜风 

分 类 号：R758.41[医药卫生—皮肤病学与性病学]