Oxidative stress activated by Keap-1/Nrf2 signaling pathway in pathogenesis of preeclampsia

We aimed to investigate the effect of Keap1/Nrf2 pathway on the biologic function of trophoblast cells in the oxidative stress model at the cellular level, and analyze the expression levels and clinical significance of Keap1/Nrf2 related antioxidant factors in placental tissues of preeclampsia (PE) patients at clinical level. In this study, we found that under hypoxia/reoxygenation conditions, the activities of oxidative stress-related enzymes (CAT, GSH-Px, SOD) in HTR8/SVneo cells were significantly lower than those before treatment (P<0.01). The activities of CAT, GSH-Px and SOD in HTR8/SVneo cells in siRNA+H/R group decreased significantly (P<0.01), which indicated the important defensive effect of Keap1/Nrf2 pathway in oxidative stress. Compared with Nrf2 siRNA+H/R group, Si-NC+H/R group had CAT, GSH-Px and SOD activities decreasing, which were similar to those in the H/R group. Moreover, the activities of oxidative stress-related active enzymes in patients with preeclampsia were further confirmed by detecting and comparing the activities of CAT, GSH-Px and SOD in placental tissues. The results showed that the activities of SOD (P<0.001), GSH-Px (P<0.01) and CAT (P<0.01) in placental tissues of patients with PE were significant different from those of normal placental tissues. The expression level of Keap1 in placenta of patients with PE was slightly lower than that of normal placenta, while the expression of Nrf2 and HO-1 in placenta of patients with PE were significantly higher than those of normal placenta, which implicated the importance of Keap-1/Nrf2 pathway in PE.