子痫前期中活性氧诱导线粒体功能障碍抑制滋养细胞上皮-间质转化

doi:10.12280/gjfckx.20251306

摘要/Abstract

摘要：

目的：探讨HTR8/SVneo细胞系内氧化应激引发子痫前期（preeclampsia，PE）的可能病理机制。方法：收集1例重度PE患者的胎盘组织，使用生物透视电镜观察线粒体形态。分别使用10、20和50 μmol/L的H₂O₂处理HTR8/SVneo细胞24 h，同时设置对照组，采用流式细胞术检测各组细胞内活性氧（reactive oxygen species，ROS）水平、线粒体膜电位及线粒体通透性转换孔（mitochondrial permeability transition pore，MPTP）开放程度，并使用蛋白质印迹法检测各组细胞内上皮-间质转化（epithelial-mesenchymal transition，EMT）相关标志蛋白水平。结果：重度PE患者胎盘组织中线粒体嵴肿胀、断裂、减少或消失（呈空泡状）。在HTR8/SVneo细胞中，随着H₂O₂浓度的增加，ROS水平逐渐增加，细胞内线粒体膜电位逐渐下降，MPTP开放程度逐渐升高，上皮钙黏蛋白（E-cadherin）表达量逐渐增加，神经钙黏蛋白（N-cadherin）、波形蛋白（Vimentin）表达量逐渐减少。结论：初步证实PE患者胎盘组织中线粒体形态发生变化，ROS水平增加可能通过诱导线粒体功能障碍并抑制EMT进程参与PE发病。

关键词: 先兆子痫, 活性氧, 膜电位, 线粒体, 线粒体通透性转换孔, 上皮-间质转化

Abstract:

Objective: To investigate the potential pathological mechanism of oxidative stress induced preeclampsia (PE) in HTR8/SVneo cell line. Methods: Placental tissue from one patient with severe PE was collected, and mitochondrial morphology was observed using biological transmission electron microscopy. HTR8/SVneo cells were treated with 10, 20, and 50 μmol/L H₂O₂ for 24 hours, with a control group established concurrently. Intracellular reactive oxygen species (ROS) levels, mitochondrial membrane potential, and the opening degree of the mitochondrial permeability transition pore (MPTP) were detected by flow cytometry in each group. Protein levels of epithelial-mesenchymal transition (EMT)-related marker proteins were measured by western blotting. Results: In the placental tissue from the severe PE patient, mitochondrial cristae appeared swollen, fractured, reduced, or disappeared (appearing vacuolated). In HTR8/SVneo cells, with increasing concentrations of H₂O₂, intracellular ROS levels gradually increased, the mitochondrial membrane potential gradually decreased, and MPTP opening degree progressively increased. The expression of the epithelial marker E-cadherin gradually increased, while the expression of the mesenchymal markers N-cadherin and Vimentin gradually decreased. Conclusions: This study preliminarily confirms altered mitochondrial morphology in the placental tissues of PE patients. Increased ROS levels may be involved in the pathogenesis of PE by inducing mitochondrial dysfunction and inhibiting the EMT process.

Key words: Pre-eclampsia, Reactive oxygen species, Membrane potential, Mitochondrial, Mitochondrial permeability transition pore, Epithelial-mesenchymal transition

彭景, 李天静, 张姝怡, 陈苗苗. 子痫前期中活性氧诱导线粒体功能障碍抑制滋养细胞上皮-间质转化[J]. 国际妇产科学杂志, 2026, 53(4): 468-473.

PENG Jing, LI Tian-jing, ZHANG Shu-yi, CHEN Miao-miao. Reactive Oxygen Species Induce Mitochondrial Dysfunction and Inhibit Epithelial-Mesenchymal Transition in Trophoblasts in Preeclampsia[J]. Journal of International Obstetrics and Gynecology, 2026, 53(4): 468-473.

图/表 7

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组别	n	ROS荧光强度
对照组	3	13 381.470±972.958
10 μmol/L H₂O₂组	3	16 353.533±792.802^a
20 μmol/L H₂O₂组	3	21 033.767±680.448^ab
50 μmol/L H₂O₂组	3	29 746.773±1 664.742^abc
F		127.332
P		<0.001

组别	n	ROS荧光强度
对照组	3	13 381.470±972.958
10 μmol/L H₂O₂组	3	16 353.533±792.802^a
20 μmol/L H₂O₂组	3	21 033.767±680.448^ab
50 μmol/L H₂O₂组	3	29 746.773±1 664.742^abc
F		127.332
P		<0.001

组别	n	线粒体膜电位荧光比值	MPTP荧光强度
对照组	3	0.052±0.009	30 531.933±471.537
10 μmol/L H₂O₂组	3	0.140±0.019^a	20 716.267±1 049.623^a
20 μmol/L H₂O₂组	3	0.250±0.025^ab	16 585.467±873.578^ab
50 μmol/L H₂O₂组	3	0.343±0.021^abc	12 030.560±972.318^abc
F		124.271	246.127
P		<0.001	<0.001

组别	n	线粒体膜电位荧光比值	MPTP荧光强度
对照组	3	0.052±0.009	30 531.933±471.537
10 μmol/L H₂O₂组	3	0.140±0.019^a	20 716.267±1 049.623^a
20 μmol/L H₂O₂组	3	0.250±0.025^ab	16 585.467±873.578^ab
50 μmol/L H₂O₂组	3	0.343±0.021^abc	12 030.560±972.318^abc
F		124.271	246.127
P		<0.001	<0.001

组别	n	E-cadherin	N-cadherin	Vimentin
对照组	3	0.358±0.013	1.984±0.007	2.882±0.003
10 μmol/L H₂O₂组	3	0.547±0.005^a	1.950±0.010^a	2.851±0.012^a
20 μmol/L H₂O₂组	3	0.576±0.070^a	1.916±0.005^ab	2.711±0.011^ab
50 μmol/L H₂O₂组	3	0.913±0.120^abc	1.655±0.005^abc	2.378±0.017^abc
F		43.395	1 267.1	1 183.6
P		<0.001	<0.001	<0.001