HIF-1α及脂质氧化应激标记物对早期妊娠结局的影响研究

Study on the effects of HIF-1α and lipid oxidative stress markers on early pregnancy outcomes

摘要

目的 探究早孕期母体缺氧诱导因子1-α(HIF-1α)诱导的氧化损伤对早期妊娠结局的影响,并分析脂质氧化损伤标记物对氧磷酶-1(PON-1)和8-异前列腺素F_2α(8-iso-PGF_2α)预测早期妊娠丢失的临床价值。方法 选取2020年9月至2021年9月于青岛市市立医院妇产科就诊的早期妊娠孕妇61例为研究对象,其中早期先兆流产19例、胚胎停育20例、正常妊娠22例.收集孕妇基本信息,采集血样,通过酶联免疫法(ELISA)检测血清HIF-1α、PON-1和8-iso-PGF_2α水平.采用受试者工作特征(ROC)曲线分析本实验中生物指标的灵敏度、特异度并计算曲线下面积(AUC)。结果 先兆流产组和胚胎停育组HIF-1α、8-iso-PGF_2α水平均高于正常妊娠组,PON-1水平均低于正常妊娠组,且胚胎停育组8-iso-PGF_2α水平高于先兆流产组,差异有统计学意义(F值分别为16.21、20.65、21.46,P<0.01);Pearson相关性分析显示血清HIF-1α和8-iso-PGF_2α呈正相关性(r=0.357,P<0.05),血清中PON-1与HIF-1α、8-iso-PGF_2α均呈负相关性(r值分别为-0.420、-0.309,P<0.05);ROC曲线中HIF-1α、PON-1、8-iso-PGF_2α及HIF-1α和8-iso-PGF_2α二者联合指标预测早期妊娠丢失的AUC分别为0.854、0.886、0.815、0.929,灵敏度分别为79.49%、74.36%、69.23%、84.62%,特异度分别为81.82%、95.45%、86.36%、95.45%。结论 母体血清HIF-1α、8-iso-PGF_2α、PON-1水平与早期妊娠结局有关,HIF-1α和8-iso-PGF_2α水平升高、PON-1降低者易发生早期妊娠丢失.血清HIF-1α和8-iso-PGF_2α联合对早期妊娠丢失具有较高的临床预测价值.

Abstract

Objective To explore the effects of oxidative damage induced by hypoxia-inducible factor 1-α (HIF-1α) on early pregnancy outcomes and analyze the clinical value of lipid oxidative damage markers, paraoxonase-1 (PON-1) and 8-iso-prostaglandin F_2α (8-iso-PGF_2α), in predicting early pregnancy loss. Methods A total of 61 early pregnant women who visited the department of obstetrics and gynecology at Qingdao Municipal Hospital from September 2020 to September 2021 were selected for the study. Among them, 19 cases were early threatened abortion, 20 cases embryo arrest, and 22 cases normal pregnancy. Basic maternal information was collected, and blood samples were obtained. Serum levels of HIF-1α, PON-1, and 8-iso-PGF_2α were measured by enzyme-linked immunosorbent assay (ELISA). The sensitivity and specificity of these biomarkers were analyzed using the receiver operating characteristic (ROC) curve, and the area under the curve (AUC) was calculated. Results The levels of HIF-1α and 8-iso-PGF_2α were higher in the threatened abortion and embryonic arrest groups compared to the normal pregnancy group, while PON-1 levels were lower in these groups, and the embryonic arrest group had higher 8-iso-PGF_2α levels than the threatened abortion group, with statistically significant differences (F=16.21, 20.65, and 21.46, respectively, P<0.01). Pearson correlation analysis indicated a positive correlation between serum HIF-1α and 8-iso-PGF_2α (r=0.357, P<0.05), while PON-1 was negatively correlated with both HIF-1α and 8-iso-PGF_2α (r=-0.420 and -0.309, respectively, P<0.05). The AUC values for predicting early pregnancy loss using HIF-1α, PON-1, 8-iso-PGF_2α, and the combined markers of HIF-1α and 8-iso-PGF_2α were 0.854, 0.886, 0.815, and 0.929, with corresponding sensitivities of 79.49%, 74.36%, 69.23% and 84.62%, and specificity of 81.82%, 95.45%, 86.36% and 95.45%, respectively. Conclusion Maternal serum levels of HIF-1α, 8-iso-PGF_2α, and PON-1 are associated with early pregnancy outcomes. Elevated HIF-1α and 8-iso-PGF_2α levels and reduced PON-1 levels increase the risk of early pregnancy loss. The combination of serum HIF-1α and 8-iso-PGF_2α has high clinical predictive value for early pregnancy loss.

关键词

早期妊娠 / 妊娠丢失 / 脂质氧化应激 / 缺氧诱导因子1-α / 8-异前列腺素F _2α / 对氧磷酶

Key words

early pregnancy / pregnancy loss / lipid oxidative stress / hypoxia-inducible factors 1-α / 8-iso-prostaglandin F _2α / paraoxonase

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基金资助

青岛市卫健委基金项目(2020GWJZD010)