子痫前期中Nrf2和NQO1的关系及NQO1对HTR-8/SVneo细胞侵袭力影响的研究

The Relationship Between Nrf2 and NQO1 in Preeclampsia and the Effect of NQO1 on the Invasiveness of htr-8/svneo Cells

目的探讨子痫前期中核因子E2相关因子2(Nrf2)和醌氧化还原酶1(NQO1)的关联性及HTR-8/SVneo细胞中NQO1对其侵袭力的影响。方法选取子痫前期患者74例,同时选取正常妊娠妇女74例,在剖宫产前1d采集两组血浆样本,应用酶联免疫吸附试验测量Nrf2和NQO1水平,并进行Pearson相关分析。使用Nrf2诱导剂(tBHQ)与抑制剂(ML385)、NQO1诱导剂(2-HBA)与抑制剂(Dicoumarol)分别对HTR-8/SVneo细胞进行预处理,再应用双氧水处理或空白处理4h,对细胞模型(HTR-8/SVneo)中Nrf2和NQO1水平以及NQO1mRNA具备的相对表达水平进行检测,分析其对HTR-8/SVneo细胞的影响。结果子痫前期患者的Nrf2和NQO1水平均低于对照组(P<0.05);子痫前期患者的Nrf2和NQO1表达水平呈正相关(P<0.05);相较于对照组,双氧水组和tBHQ组细胞中Nrf2和NQO1蛋白和NQO1mRNA相对表达水平更高,差异有统计学意义(P<0.05);ML385组与对照组细胞中Nrf2和NQO1蛋白和NQO1mRNA相对表达水平差异无统计学意义(P>0.05);相较于双氧水组,双氧水联合ML385组细胞中Nrf2和NQO1蛋白和NQO1mRNA相对表达水平均更低(P<0.05)。结论子痫前期患者Nrf2、NQO1水平下降,其会导致机体抗氧化能力减弱,在氧化应激条件下,Nrf2可激活NQO1从而使HTR-8/SVneo细胞侵袭力增强。

Objective To investigate the relationship between nuclear factor E2 related factor 2(Nrf2)and quinone oxidoreductase-1(NQO1)in preeclampsia and the effect of NQO1 on the invasiveness of htr-8/svneo cells.Methods 74 cases of preeclampsia and 74 cases of normal pregnant women were selected.The plasma samples were collected one day before cesarean section.The levels of Nrf2 and NQO1 were measured by enzyme-linked immunosorbent assay(ELISA),and Pearson correlation analysis was performed.Htr-8/svneo cells were pretreated with Nrf2 inducer(TBHQ),NQO1 inducer(2-hbas),Nrf2 inhibitor(ml385)and NQO1 inhibitor(dicoumarol),respectively.Then,htr-8/svneo cells were pretreated with hydrogen peroxide or blank treatment for 4 h.The relative expression level of NQO1 mRNA and Nrf2 and NQO1 mRNA in htr-8/svneo cell model were detected to analyze the invasiveness of htr-8/svneo cells.Results The levels of Nrf2 and NQO1 in preeclampsia patients were lower than those in the control group,the difference was statistically significant(P<0.05);the expression levels of Nrf2 and NQO1 in preeclampsia patients were positively correlated(P<0.05);compared with the control group,the relative expression levels of Nrf2 and NQO1 protein and NQO1 mRNA in cells of hydrogen peroxide group and TBHQ group were higher,and the difference was statistically significant(P<0.05);ml385 There was no significant difference in the relative expression levels of Nrf2,NQO1 protein and NQO1 mRNA between the two groups(P>0.05);compared with the hydrogen peroxide group,the relative expression levels of Nrf2 and NQO1 proteins and NQO1 mRNA in the cells of the hydrogen peroxide combined with ml385 group were lower,and the difference was statistically significant(P<0.05).Conclusion The decrease of plasma Nrf2 and NQO1 levels in patients with preeclampsia may lead to the decrease of antioxidant capacity.Under oxidative stress,Nrf2 can activate NQO1 in htr-8/svneo cells,thus enhancing cell invasion.