无机砷对Chang肝细胞核转录因子Nrf2及其下游抗氧化酶mRNA表达的影响

Effects of inorganic arsenic on mRNA expression of Nrf2 and Nrf2-regulated downstream anti-oxidant enzymes in Chang hepatocytes

目的观察亚砷酸钠(NaAsO2)对Chang肝细胞株核转录因子Nrf2及Nrf2调控的下游抗氧化酶醌氧化还原酶1(NQO1)和血红素单加氧酶-1(HO-1)mRNA表达的影响。方法分别以不同浓度NaAsO2(5、10、25和50μmol/L)染毒人类Chang肝细胞株6h,采用RT-PCR法测定Nrf2、NQO1和HO-1的mRNA表达水平。结果 5、10、25和50μmol/L NaAsO2暴露6h,Nrf2的mRNA表达分别为对照组的(100.74±3.70)%、(105.96±1.75)%、(101.76±1.01)%和(101.81±6.33)%,与对照组比较,差异未见统计学意义(P>0.05);各暴露组NQO1的mRNA表达均较对照组相比显著增加(P<0.05),分别为对照组的(106.52±3.11)%、(113.27±2.84)%、(111.96±6.96)%和(107.33±2.76)%;NaAsO2暴露还能够显著诱导HO-1的mRNA表达增强,且具有剂量-效应关系,差异具有统计学意义(P<0.01)。5、10、25和50μmol/L NaAsO2暴露,HO-1的mRNA表达分别为对照组的(186.92±1.75)%、(194.08±2.75)%、(196.93±2.55)%和(200.02±0.83)%。结论无机砷暴露未显著增强Chang肝细胞核转录因子Nrf2的转录,却能够显著提高Nrf2调控的下游抗氧化酶NQO1和HO-1的mRNA表达水平。

Objective To study the effects of inorganic arsenic on mRNA expression of transcription factor Nrf2 and Nrf2-regulated downstream anti-oxidant enzymes,NADPH：quinine oxidoreductase 1（NQO1）and heme oxygenase 1（HO-1）in Chang hepatocytes.Methods Chang hepatocytes were treated with 5,10,25 and 50μmol/L of sodium arsenite（NaAsO2）for 6h,and RT-PCR were then performed to detect the mRNA expression of Nrf2,NQO1 and HO-1.Results When exposed to 5,10,25 and 50μmol/L of NaAsO2,Nrf2 mRNA were（100.74±3.70）%,（105.96±1.75）%,（101.76±1.01）% and（101.81±6.33）% of control,showing no statistic significance（P0.05）.NQO1 mRNA expression were significantly increased（P0.05）,and the levels of NQO1 mRNA were（106.52±3.11）%,（113.27±2.84）%,（111.96±6.96）% and（107.33±2.76）% of control,respectively.Moreover,HO-1 mRNA expression were also significantly induced by sodium arsenite exposure,and a definite dose-effect relationship was confirmed（P0.01）.Conclusion No elevation of Nrf2 transcription was found,while inorganic arsenic could increase the Nrf2-regulated NQO1 and HO-1 mRNA expression in human hepatocytes.