Department of Pharmacy, Urumqi Youai Hospital, Urumqi, 830000, China.
Department of Pharmacy, Xinjiang Production & Construction Corps Hospital, Urumqi, 830000, China.
Placenta. 2023 Dec;144:55-63. doi: 10.1016/j.placenta.2023.11.008. Epub 2023 Nov 18.
Pre-eclampsia (PE) is a pregnancy complication that can lead to maternal, fetal, and neonatal deaths in clinical practice. Accumulation of trophoblastic reactive oxygen species (ROS), which could result in oxidative stress and cell apoptosis, is considered to play an important role in PE pathology. It has been reported that aspirin has a positive effect on PE treatment in high-risk pregnant women.
In vitro, extravillous trophoblast cell line (HTR-8/SVneo) were treated with hydrogen peroxide (HO, 150 μM) after the presence of aspirin (90 and 120 μM) with or without GKT137831 (a Nox4 inhibitor, 20 μM). A series of experiments including CCK-8 assays, flow cytometry, biochemical testing, and Western Blotting etc. verified the protective effects and potential mechanisms of aspirin against oxidative stress-induced damage in PE.
Our results demonstrated that HO induces oxidative stress and apoptosis in HTR8/SVneo cells. However, aspirin pretreatment rescue cell viability and reduce LDH activity of HTR-8/SVneo cells. Aspirin can suppress the ROS overproduction and MDA level while increase SOD content and CAT activity. In addition, aspirin pretreatment significantly alleviated cell apoptosis and suppressed the expression of Nox4 and its subunits (p22phox and p47phox) at protein and mRNA levels. The above results were more obvious after the combination of aspirin with GKT137831.
This study demonstrated that aspirin protects human trophoblasts against HO-induced oxidative stress and cell apoptosis via suppressing NADPH/ROS pathway. These findings provide novel insights for the application of aspirin as a protective and curative agent against PE.
子痫前期（PE）是一种妊娠并发症，在临床实践中可导致母婴、胎儿和新生儿死亡。滋养细胞活性氧（ROS）的积累，可能导致氧化应激和细胞凋亡，被认为在 PE 病理中发挥重要作用。据报道，阿司匹林对高危孕妇的 PE 治疗有积极作用。
在体外，绒毛外滋养细胞系（HTR-8/SVneo）在存在阿司匹林（90 和 120 μM）后用过氧化氢（HO，150 μM）处理，并加入或不加入 GKT137831（Nox4 抑制剂，20 μM）。一系列实验，包括 CCK-8 测定、流式细胞术、生化测试和 Western Blotting 等，验证了阿司匹林对 PE 诱导的氧化应激损伤的保护作用及其潜在机制。
我们的结果表明，HO 诱导 HTR8/SVneo 细胞发生氧化应激和细胞凋亡。然而，阿司匹林预处理可挽救 HTR-8/SVneo 细胞的活力并降低 LDH 活性。阿司匹林可抑制 ROS 过度产生和 MDA 水平，同时增加 SOD 含量和 CAT 活性。此外，阿司匹林预处理可显著减轻细胞凋亡，并抑制 Nox4 及其亚基（p22phox 和 p47phox）的蛋白和 mRNA 表达。在阿司匹林与 GKT137831 联合使用后，上述结果更为明显。
本研究表明，阿司匹林通过抑制 NADPH/ROS 途径保护人滋养细胞免受 HO 诱导的氧化应激和细胞凋亡。这些发现为阿司匹林作为预防和治疗 PE 的保护和治疗剂的应用提供了新的见解。
