摘 要：为探索微小核糖核酸RNA-128-3p（miR-128-3p）调控沉默信息调节因子2相关酶1（SIRT1）/缺氧诱导因子-1α（HIF-1α）通路对妊娠滋养层细胞增殖和侵袭的影响，收集2023年10月—2024年10月邯郸市中心医院子痫前期患者和正常足月孕妇胎盘组织，利用实时荧光定量聚合酶链式反应测定组织和细胞中miR-128-3p的表达。培养JEG-3细胞并分别转染anti-miR-128-3p、si-SIRT1，同时设置阴性对照，采用四甲基噻唑蓝（MTT）法测定JEG-3细胞活力，Transwell试验测定JEG-3细胞的迁移和侵袭，Western blot法检测细胞周期依赖性蛋白激酶抑制因子1A（P21）、基质金属蛋白酶-2（MMP-2）、E-钙黏附素（E-cadherin）、SIRT1、细胞周期蛋白D1（Cyclin D1）、HIF-1α的蛋白表达，双荧光素酶试验验证miR-128-3p与SIRT1的靶向关系。试验结果表明：子痫前期组胎盘组织miR-128-3p水平比正常胎盘组织高（P<0.05）；抑制miR-128-3p表达后，P21、E-cadherin、HIF-1α蛋白表达量下降，而细胞存活率、迁移细胞数、侵袭细胞数及MMP-2、Cyclin D1、SIRT1蛋白表达升高（P<0.05）。SIRT1是miR-128-3p的靶基因，抑制miR-128-3p和SIRT1表达后，上述指标的表达均呈相反趋势（P<0.05）。过表达miR-128-3p可能通过调控SIRT1/HIF-1α通路抑制妊娠滋养层细胞增殖和侵袭。

关键词：miR-128-3p；SIRT1；缺氧诱导因子-1α；子痫前期；妊娠滋养层细胞增殖和侵袭
中图分类号：R714.256；R714.24             文献标志码：A          DOI：10.3969/j.issn.1007-7146.2025.05.009

Abstract: To explore the effects of microRNA-128-3p (miR-128-3p) on proliferation and invasion of gestational trophoblast cells by modulating silent information regulator 2 homolog 1(SIRT1)/hypoxia inducible factor-1α (HIF-1α) pathway, the placental tissues were collected from preeclampsia patients and normal full-term pregnant women who gave birth in the Handan Central Hospital from October 2023 to October 2024. The real-time fluorescence quantitative polymerase chain reaction experiment was performed to detect miR-128-3p in tissues and cells. JEG-3 cells were cultured and transfected with anti-miR-128-3p, si-SIRT1, and negative controls, respectively. Tetramethylthiazole blue (MTT) assay was used to detect the viability of JEG-3 cells; transwell experiment was applied to measure the migration and invasion of JEG-3 cells; Western blot was applied to measure expression of cycle-dependent protein kinase inhibitor 1A (P21), matrix metalloproteinase 2 (MMP-2), E-cadherin (E-Cadherin), SIRT1, Cyclin D1(Cyclin D1), HIF-1α protein; dual luciferase assay was used to validate the targeting relationship between miR-128-3p and SIRT1. The experimental results indicate that, the expression level of miR-128-3p in placental tissues of preeclampsia group was higher than that of normal placental tissues (P<0.05). After inhibiting the expression of miR-128-3p, the expression of P21, E-cadherin and HIF-1α decreased, while the cell survival rate, the number of migrating cells and the number of invading cells, and the protein expressions of MMP-2, Cyclin D1 and SIRT1 increased (P<0.05). SIRT1 was the target gene of miR-128-3p, after simultaneously inhibiting the expression of miR-128-3p and SIRT1, the above indicators showed opposite expressions (P<0.05). Overexpression of miR-128-3p may inhibit the proliferation and invasion of gestational trophoblast cells by modulating SIRT1/HIF-1α pathway.
Key words: miR-128-3p; SIRT1; hypoxia inducible factor-1α; preeclampsia; pregnancy trophoblast cell proliferation and invasion
（Acta Laser Biology Sinica, 2025, 34(5): 459-465）