孕妇孕中期血清HIF-1α和CXCL6水平对子痫前期及妊娠结局的预测价值分析

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摘要 目的: 探讨孕妇孕中期血清缺氧诱导因子-1α（HIF-1α）和趋化因子配体6（CXCL6）水平对子痫前期（preeclampsia,PE）及妊娠结局的预测价值评估。方法: 纳入2020年1月—2022年1月于西北妇女儿童医院分娩并定期产检的PE患者140例（PE组）,根据病情严重程度进一步分为轻度组（66例）和重度组（74例）。同时纳入单纯妊娠高血压疾病患者140例（妊娠高血压组）,同期产检正常者100例为对照组。采用ELISA法检测受试者血清缺氧诱导因子（hypoxia inducible factor-1α,HIF-1α）、趋化因子配体6（chemokine C-C motif ligand 6,CXCL6）水平;采用受试者工作特征（ROC）曲线评价血清HIF-1α、CXCL6水平及其联合对PE及妊娠结局的预测价值;采用Pearson法分析血清HIF-1α、CXCL6水平及与实验室指标的相关性分析;采用进行Logistic回归分析PE妊娠结局不良的影响因素。结果: 对照组、妊娠高血压组、PE组患者HIF-1α、CXCL6水平依次增高,两两比较差异有统计学意义。相较于轻度组,重度组的舒张压、收缩压、胆固醇（TC）、甘油三酯（TG）、低密度脂蛋白（LDL-C）、白介素-1β（IL-1β）、白细胞介素-6（IL-6）、肿瘤坏死因子-α（TNF-α）、HIF-1α、CXCL6水平显著升高,高密度脂蛋白（HDL-C）水平显著降低。ROC结果显示,血清中HIF-1α、CXCL6水平及二者联合诊断PE的严重程度的AUC分别为0.730、0.751、0.858,其中联合预测AUC显著高于二者单独预测AUC（Z=3.367、2.940,P<0.05）。相较于妊娠结局良好组,妊娠结局不良的舒张压、收缩压、TC、TG、LDL-C、IL-1β、IL-6、TNF-α、HIF-1α、CXCL6水平显著升高,HDL-C水平显著降低。PE血清中HIF-1α的水平分别与CXCL6、IL-1β、IL-6、TNF-α呈正相关（r=0.611、0.639、0.612、0.569,P<0.05）。CXCL6的水平分别与IL-1β、IL-6、TNF-α呈正相关（r=0.605、0.584、0.593,P<0.05）。多因素Logistic分析结果显示,IL-1β、TNF-α、HIF-1α、CXCL6均是PE发生妊娠结局不良的独立危险因素。ROC结果显示,血清中HIF-1α、CXCL6水平及二者联合预测PE疾病发生妊娠结局不良的AUC分别为0.754、0.775、0.854,其中联合预测AUC显著高于二者单独预测AUC（Z=6.295、6.912,P<0.05）。结论: PE孕妇血清HIF-1α、CXCL6水平升高,PE病情程度关系密切,二者有望成为PE及孕妇不良妊娠结局的发生的预测因子。

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	曹香汆
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关键词 ：先兆子痫, 不良分娩结局, 缺氧诱导因子-1α, 趋化因子配体6, 预测

Abstract：Objective To evaluate the predictive value of serum hypoxia inducible factor-1α (HIF-1α) and chemokine C-C motif ligand 6(CXCL6) levels in the second trimester of pregnancy for preeclampsia (PE) and pregnancy outcome. Methods A total of 140 PE patients (PE group) who delivered in northwest women's and children's hospital from January 2020 to January 2022 and had regular antenatal examination were included. They were further divided into mild group (66 cases) and severe group (74 cases) according to the severity of the disease.140 patients with simple hypertensive disorder complicating pregnancy (hypertensive disorder complicating pregnancy) were included. The control group consisted of 100 normal cases in the same period. The levels of serum HIF-1α and CXCL6 were detected by ELISA; the predictive value of serum HIF-1α, CXCL6 levels and their combination for PE and pregnancy outcome was evaluated by receiver operating characteristic (ROC) curve. Analysis of serum HIF-1α by Pearson method, CXCL6 level and correlation analysis with laboratory indicators; Logistic regression was used to analyze the influencing factors of PE pregnancy outcome. Results The levels of serum HIF-1α and CXCL6 in PE group were obviously higher than those in control group. Compared with the mild group, the diastolic blood pressure, systolic blood pressure, levels of TC, TG, LDL-C, IL-1β, IL-6, TNF-α, HIF-1α, CXCL6 in the severe group were obviously higher, while the level of HDL-C was obviously lower. ROC results showed that HIF-1α in serum, The level of CXCL6 and the AUC of the combined diagnosis of PE were 0.730, 0.751 and 0.858, respectively. The combined prediction of AUC was significantly higher than the two independent prediction of AUC (Z=3.367, 2.940, P<0.05). Compared with the good pregnancy outcome group, the diastolic blood pressure, systolic blood pressure, levels of TC, TG, LDL-C, IL-1β, IL-6, TNF-α, HIF-1α, CXCL6 with poor pregnancy outcome were obviously higher, while the level of HDL-C was obviously lower. HIF-1α in PE serum And the level of CXCL6 and IL-1βrespectively, IL-6, TNF-α There was a positive correlation (r=0.611, 0.639, 0.612, 0.569, P<0.05). The level of CXCL6 is different from IL-1β, IL-6, TNF-α There was a positive correlation (r=0.605, 0.584, 0.593, P<0.05). Multi-factor logistic analysis results show that IL-1β, TNF-α, HIF-1α, CXCL6 was an independent risk factor for poor pregnancy outcome in PE. ROC results showed that the AUC of serum HIF-1α, CXCL6 levels and their combination to predict the adverse pregnancy outcome of PE disease was 0.754, 0.775 and 0.854, respectively, the AUC of combined prediction was obviously higher than that of the two alone (Z=6.295, 6.912, P<0.05). Conclusion The levels of serum HIF-1α and CXCL6 in pregnant women with PE are increased, and are closely related to the severity of PE. They are expected to be predictive factors of PE and adverse pregnancy outcomes of pregnant women.

Key words： preeclampsia bad delivery outcome hypoxia inducible factor-1α chemokine C-C motif ligand 6 prediction

收稿日期: 2023-03-21

中图分类号:

R714.24

基金资助:中国孕产妇子痫前期风险预测研究项目（2021AMCHS003）

通讯作者: 谢丹,E-mial：XDwyh880425@163.com

引用本文:

曹香汆, 谢丹, 白芡蓉. 孕妇孕中期血清HIF-1α和CXCL6水平对子痫前期及妊娠结局的预测价值分析[J]. 湖南师范大学学报(医学版), 2023, 20(4): 96-101. CAO Xiangcuan, XIE Dan, BAI Qianrong. Evaluation of the predictive value of serum HIF-1α and CXCL6 levels in the second trimester of pregnancy for preeclampsia and pregnancy outcome. HuNan ShiFan DaXue XueBao(YiXueBan), 2023, 20(4): 96-101.

链接本文:

http://yxb.hunnu.edu.cn/CN/ 或 http://yxb.hunnu.edu.cn/CN/Y2023/V20/I4/96

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