Feng Hao, Wang Li, Zhang Guoxiang, Zhang Zhiwei, Guo Wei
Department of Obstetrics and Gynecology, Shandong Provincial Qianfoshan Hospital, The First Hospital Affiliated with Shandong First Medical University Jinan, Shandong, China.
Int J Clin Exp Pathol. 2020 Mar 1;13(3):382-392. eCollection 2020.
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.
我们旨在在细胞水平上研究Keap1/Nrf2通路在氧化应激模型中对滋养层细胞生物学功能的影响，并在临床水平上分析子痫前期（PE）患者胎盘组织中Keap1/Nrf2相关抗氧化因子的表达水平及临床意义。在本研究中，我们发现，在缺氧/复氧条件下，HTR8/SVneo细胞中氧化应激相关酶（CAT、GSH-Px、SOD）的活性显著低于处理前（P<0.01）。siRNA+H/R组HTR8/SVneo细胞中CAT、GSH-Px和SOD的活性显著降低（P<0.01），这表明Keap1/Nrf2通路在氧化应激中具有重要的防御作用。与Nrf2 siRNA+H/R组相比，Si-NC+H/R组CAT、GSH-Px和SOD活性降低，与H/R组相似。此外，通过检测和比较胎盘组织中CAT、GSH-Px和SOD的活性，进一步证实了子痫前期患者氧化应激相关活性酶的活性。结果显示，PE患者胎盘组织中SOD（P<0.001）、GSH-Px（P<0.01）和CAT（P<0.01）的活性与正常胎盘组织有显著差异。PE患者胎盘中Keap1的表达水平略低于正常胎盘，而PE患者胎盘中Nrf2和HO-1的表达显著高于正常胎盘，这提示了Keap-1/Nrf2通路在PE中的重要性。
