Liu Xin, Wan Jun, Wei Ming, Tong Yanan, Yao Zhaomin
Department of Nuclear Medicine, General Hospital of Northern Theater Command, Shenyang, Liaoning, China.
Department of Blood Transfusion, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
Immun Inflamm Dis. 2024 Dec;12(12):e70097. doi: 10.1002/iid3.70097.
Preeclampsia (PE) is a multifaceted medical condition that manifests during pregnancy, characterized by hypertension and damage to multiple organs. In PE, the placenta's impaired functionality leads to continuous hypoxia in placental tissues, which is considered the primary cause of the condition. Inhibition of hypoxia-induced injury in trophoblast cells presents a potential therapeutic strategy for PE. Edaravone (EDA) is a potent antioxidant with proven efficacy against various diseases and injuries, yet its impact on PE requires further exploration.
Placenta tissues from pregnant women, with or without PE, were collected, and levels of hypoxia-inducible factor (HIF-1α), P-AKT, AKT, and PI3K proteins were analyzed using Western blotting. An in vitro anoxia model was established by treating the human trophoblast cell line HTR-8/SVneo with cobalt chloride (CoCl). Standard techniques were employed to measure proliferation, apoptosis, and reactive oxygen species (ROS) production rates in the anoxic cells, with and without EDA treatment.
HIF-1α, P-AKT, AKT, and PI3K protein levels were significantly elevated in the placenta of the PE group compared with the control group. EDA mitigated the CoCl-induced decrease in HTR-8/SVneo cell viability and reduced apoptosis and ROS production. Furthermore, EDA counteracted the activation of the PI3K/AKT pathway in CoCl-treated trophoblasts.
EDA protected trophoblasts against hypoxic injury by inhibiting the PI3K/AKT pathway, suggesting that it may serve as a promising therapeutic option for PE.
子痫前期（PE）是一种在孕期出现的多方面病症，其特征为高血压和多器官损伤。在子痫前期中，胎盘功能受损导致胎盘组织持续缺氧，这被认为是该病症的主要病因。抑制滋养层细胞缺氧诱导的损伤为子痫前期提供了一种潜在的治疗策略。依达拉奉（EDA）是一种有效的抗氧化剂，已被证明对各种疾病和损伤有效，但其对子痫前期的影响仍需进一步探索。
收集患有或未患子痫前期的孕妇的胎盘组织，采用蛋白质免疫印迹法分析缺氧诱导因子（HIF-1α）、磷酸化AKT（P-AKT）、AKT和磷脂酰肌醇-3激酶（PI3K）蛋白的水平。通过用氯化钴（CoCl）处理人滋养层细胞系HTR-8/SVneo建立体外缺氧模型。采用标准技术测量在有无EDA处理的缺氧细胞中的增殖、凋亡和活性氧（ROS）产生率。
与对照组相比，子痫前期组胎盘组织中HIF-1α、P-AKT、AKT和PI3K蛋白水平显著升高。EDA减轻了CoCl诱导的HTR-8/SVneo细胞活力下降，并减少了细胞凋亡和ROS产生。此外，EDA抵消了CoCl处理的滋养层细胞中PI3K/AKT信号通路的激活。
EDA通过抑制PI3K/AKT信号通路保护滋养层细胞免受缺氧损伤，表明它可能是子痫前期一种有前景的治疗选择。
