Department of Obstetrics and Gynecology, The First Affiliated Hospital of Naval Medical University, Shanghai, China.
Department of Laboratory Medicine, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Gynecol Obstet Invest. 2024;89(5):387-401. doi: 10.1159/000538261. Epub 2024 Apr 17.
Necroptosis, a form of programmed cell death, can occur in the placenta of patients with preeclampsia (PE). Hydrogen sulfide (H2S) can inhibit necroptosis of human umbilical vein endothelial cells under the high glucose-induced injury. Whether H2S can protect trophoblasts against necroptosis underlying PE has not been elucidated. This study aimed to explore the protective role of H2S in trophoblast cells against necroptosis underlying PE.
This is an in vitro experimental study.
A total of 10 pregnant women with severe PE and 10 matched control normotensive pregnant women were included. The placenta tissues were extracted from participators. The human JEG-3 trophoblasts were commercially available.
The expression and localization of necrotic proteins were assayed in human placenta samples, and the effect of necrotic cell death on the proliferation and apoptosis of human JEG-3 trophoblasts was evaluated. The component expressions of inflammatory cytokine and p38MAPK signaling pathway were measured in samples pretreated with or without NaHS (H2S donor) and SB203580 (p38 inhibitor).
RIPA1, RIPA3, and p-p38 levels were significantly higher in PE placental tissue, whereas cystathionine β-synthase expression was decreased. In JEG-3 trophoblasts, necroptosis increased apoptotic cell numbers, suppressed cell proliferation, increased inflammatory cytokine expression, and increased p38MAPK activation, which can be prevented by NaHS.
In the present study, we did not provide sufficient evidence that necroptosis was a part of the pathogenesis of PE.
We proposed the putative role of necroptosis in early-onset PE, reflected by the blockage of caspase-8/3 and increased expression of RIPA1 and RIPA3 in PE placenta tissues. Furthermore, we demonstrated that exogenous H2S protected cytotrophoblasts against ceramide-induced necroptosis via the p38MAPK pathway.
细胞程序性死亡的一种形式——坏死性凋亡，可发生在子痫前期（PE）患者的胎盘组织中。在高糖诱导损伤下，硫化氢（H2S）可以抑制人脐静脉内皮细胞的坏死性凋亡。H2S 是否可以保护滋养细胞免受子痫前期相关的坏死性凋亡尚未阐明。本研究旨在探讨 H2S 对滋养细胞抵抗子痫前期相关坏死性凋亡的保护作用。
这是一项体外实验研究。
共纳入 10 例重度 PE 孕妇和 10 例匹配的正常血压孕妇。从参与者中提取胎盘组织。人 JEG-3 滋养层细胞可商购获得。
检测人胎盘组织中坏死蛋白的表达和定位，评估坏死细胞死亡对人 JEG-3 滋养层细胞增殖和凋亡的影响。在预处理或未预处理 NaHS（H2S 供体）和 SB203580（p38 抑制剂）的样本中测量炎症细胞因子和 p38MAPK 信号通路的组成表达。
PE 胎盘组织中 RIPA1、RIPA3 和 p-p38 水平显著升高，胱硫醚β-合酶表达降低。在 JEG-3 滋养层细胞中，坏死性凋亡增加了凋亡细胞数量，抑制了细胞增殖，增加了炎症细胞因子的表达，并增加了 p38MAPK 的激活，而这些作用可以被 NaHS 所阻止。
在本研究中，我们没有提供足够的证据表明坏死性凋亡是子痫前期发病机制的一部分。
我们提出了坏死性凋亡在早发型子痫前期中的潜在作用，这反映在子痫前期胎盘组织中 caspase-8/3 被阻断和 RIPA1 和 RIPA3 的表达增加。此外，我们证明了外源性 H2S 通过 p38MAPK 通路保护绒毛滋养细胞免受神经酰胺诱导的坏死性凋亡。
