Qiu Dongmei, Wu Jufei, Li Min, Wang Li, Zhu Xianggan, Chen Youguo
Department of Obstetrics and Gynecology, The First Affiliated Hospital of Soochow University, Suzhou.
Department of Obstetrics and Gynecology, Yancheng Maternity and Child Health Care Hospital.
Medicine (Baltimore). 2021 Mar 19;100(11):e23666. doi: 10.1097/MD.0000000000023666.
We aimed to investigate the effect of Kelch-like ECH-associated protein 1/NF-E2 p45-related factor 2 (Keap1/Nrf2) pathway on the biological function of trophoblast cells in oxidative stress model at the cellular level, and analyzed the expression level and clinical significance of Keap1/Nrf2 pathway and related antioxidant factors in placental tissues of Preeclampsia (PE) patients at clinical level. In present study, we found that under hypoxia/reoxygenation conditions, the activity of oxidative stress-related enzymes (CAT, GSH-Px, SOD) in HTR8/SVneo cells was significantly lower than that before treatment (P < .01). The activities of CAT, GSH-Px and SOD in HTR8/SVneo cells in SiRNA+H/R group decreased significantly (P < .01), indicating the important defense effect of Keap1/Nrf2 signaling pathway in oxidative stress. As a control group of Nrf2 SiRNA+H/R group, Si-NC+H/R group had CAT, GSH-Px and SOD activities decreasing, which was similar to that in H/R group. Moreover, the activities of oxidative stress-related active enzymes in patients with PE were further confirmed by detecting and comparing the activities of CAT, GSH-Px and SOD in placental tissues. The results showed that the activity of SOD (P < .001), GSH-Px (P < .01) and CAT (P < .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 in placenta of patients with PE was significantly higher than that of normal placenta. HO-1 expression in placenta of patients with PE was significantly higher than that of normal placenta. These results implicate the importance of Keap-1/Nrf2 pathway in PE.
我们旨在在细胞水平上研究 Kelch 样 ECH 相关蛋白 1/核因子 E2 p45 相关因子 2(Keap1/Nrf2)通路对氧化应激模型中滋养层细胞生物学功能的影响,并在临床水平分析子痫前期(PE)患者胎盘组织中 Keap1/Nrf2 通路及相关抗氧化因子的表达水平和临床意义。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),表明 Keap1/Nrf2 信号通路在氧化应激中具有重要的防御作用。作为 Nrf2 siRNA+H/R 组的对照组,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 PE 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 的表达显著高于正常胎盘。PE 患者胎盘中 HO-1 的表达显著高于正常胎盘。这些结果表明 Keap-1/Nrf2 通路在 PE 中具有重要意义。