妊娠期高血压患者血清miR...其对不良妊娠结局的预测价值_庞琪.pdf

广西医科大学学报JOURNAL OF GUANGXI MEDICAL UNIVERSITY2023 Jan；40（1）妊娠期高血压患者血清miR-142-3p、FOXM1水平及其对不良妊娠结局的预测价值*庞琪，陈蕾（中国人民解放军总医院第六医学中心，北京100037）摘要目的：分析妊娠期高血压疾病患者血清微小RNA-142-3p（miR-142-3p）、叉头框蛋白M1（FOXM1）的表达情况，并探讨FOXM1、miR-142-3p对不良妊娠结局的预测价值。方法：选取2015年6月至2020年6月在本院接受治疗并分娩的681例妊娠期高血压疾病患者作为研究组，将以上患者根据疾病严重程度划分为3组，分别是妊娠期高血压组（274例）、轻度子痫前期组（218例）、重度子痫前期组（189例）；按照患者妊娠结局分为不良妊娠结局组（298例）、正常妊娠结局组（383例）；以同期在本院分娩的正常孕妇700例作为对照组；分别对比分析研究组和对照组、不同疾病严重程度、不良妊娠结局组和正常妊娠结局组血清FOXM1、miR-142-3p表达水平差异；影响妊娠期高血压发生的Logistic回归分析；Spearman等级相关分析法分析血清FOXM1、miR-142-3p表达水平与妊娠期高血压患者病情严重程度和不良妊娠结局的相关性；ROC曲线分析血清FOXM1、miR-142-3p联合对妊娠期高血压患者不良妊娠结局的预测价值。结果：与对照组比较，妊娠期高血压患者血清FOXM1表达水平降低（P0.05），miR-142-3p表达水平升高（P0.05）；24 h尿蛋白、收缩压、FOXM1和miR-142-3p是妊娠期高血压发生的影响因素（P0.05）；随着妊娠期高血压患者病情严重程度加重，血清FOXM1表达水平降低（P0.05），血清miR-142-3p升高（P0.05）；患者病情严重程度与血清FOXM1负相关关系（P0.05），与血清miR-142-3p正相关关系（P0.05）；血清FOXM1、miR-142-3p以及二者联合预测妊娠期高血压患者不良妊娠结局的AUC分别为0.714、0.689、0.782。结论：妊娠期高血压患者血清FOXM1、miR-142-3p异常表达，与患者病情严重程度及不良妊娠结局关系密切。关键词妊娠期高血压；微小RNA-142-3p；叉头框蛋白M1；不良妊娠结局中图分类号：R714.2文献标志码：A文章编号：1005-930X（2023）01-0126-07DOI：10.16190/ki.45-1211/r.2023.01.020Serum miR-142-3p and FOXM1 levels in patients with gestational hypertension and theirpredictive value for adverse pregnancy outcomesPang Qi,Chen Lei.(The Sixth Medical Center of the General Hospital of the Peoples Liberation Army,Beijing100037,China)AbstractObjective:To analyze the expressions of serum microRNA-142-3p(miR-142-3p)and forkhead boxprotein M1(FOXM1)in patients with gestational hypertension and explore the predictive value of FOXM1 andmiR-142-3p for adverse pregnancy outcomes.Methods:681 patients with gestational hypertension who receivedtreatment and gave birth in in our hospital from June 2015 to June 2020 were selected as the study group.Theabove patients were divided into three groups according to the severity of the disease,namely gestational hyper-tension group(274 cases),mild preeclampsia group(218 cases)and severe preeclampsia group(189 cases);ac-cording to pregnancy outcomes,patients were grouped into adverse pregnancy outcome group(298 cases)andnormal pregnancy outcome group(383 cases);a total of 700 normal pregnant women who gave birth in our hospi-tal during the same period served as the control group;the differences in the expressions of serum FOXM1 andmiR-142-3p between the study group and the control group,among different disease severities,and between ad-verse pregnancy outcome group and normal pregnancy outcome group were compared and analyzed respectively;logistic regression was applied to analyze the influ-encing factors of gestational hypertension;Spearmanrank correlation was applied to analyze the correla-*基金项目：北京市卫生科技发展专项基金（No.2019-4-420）通信作者，E-mail：收稿日期：2022-10-12 126tion of serum FOXM1 and miR-142-3p expressions with disease severity and adverse pregnancy outcomes in pa-tients with gestational hypertension;ROC curves were applied to analyze the predictive value of the combinationof serum FOXM1 and miR-142-3p for adverse pregnancy outcomes in patients with gestational hypertension.Re-sults:Compared with the control group,the expression of serum FOXM1 in patients with gestational hyperten-sion decreased(P0.05),and the expression of miR-142-3p increased(P0.05);24 h urinary protein,systolicblood pressure,FOXM1 and miR-142-3p were the influencing factors of gestational hypertension(P0.05);with the aggravation of the disease severity in patients with gestational hypertension,the expression of serumFOXM1 decreased(P0.05),and the serum miR-142-3p increased(P0.05);the severity of the disease wasnegatively correlated with serum FOXM1(P0.05)and positively correlated with serum miR-142-3p(P0.05);the AUC of serum FOXM1,miR-142-3p,and their combination in predicting adverse pregnancy outcomes in pa-tients with gestational hypertension was 0.714,0.689,and 0.782,respectively.Conclusion:The abnormal expres-sions of serum FOXM1 and miR-142-3p in patients with gestational hypertension are closely related to the severi-ty of the patients disease and adverse pregnancy outcomes.Keywordsgestational hypertension;microRNA-142-3p;forkhead box protein M1;adverse pregnancy outcomes妊娠期高血压疾病是妊娠期较为常见的并发症，表现为妊娠和血压升高并存。有数据统计，妊娠期高血压发病率在5%10%1，常发生于妊娠20周后以及分娩后2周内2，是导致孕妇死亡的第二大原因3。研究发现，妊娠期高血压与产妇高龄、流产次数、高血压家族史、多胎妊娠、甲状腺功能减退等因素相关，其发病机制目前尚不清楚，与同龄健康孕妇比较，孕产妇及新生儿病死率更高，不良妊娠结局及日后患有高血压或心脑血管疾病的风险更高4。因此，探寻更有效诊断妊娠期高血压的血清标志物，对降低孕产妇致死率和不良妊娠结局具有重要意义。微小RNA（microRNA，miRNA）是非编码RNA，miRNA参与调控滋养层细胞的生物学行为，过表达miR-142-3p抑制滋养细胞的增殖、迁移和侵袭能力，诱发妊娠期子痫前期发展。研究表明，叉头框蛋白M1（forkhead box M1，FOXM1）参与滋养细胞的侵袭过程，在体外模拟妊娠期并发子痫前期胎盘中异常低表达5。动物模型验证FOXM1在妊娠期间对胰岛 细胞的增殖起调控作用，FOXM1表达水平降低抑制胰岛细胞的增殖6。研究发现，miR-142-3p可负调控FOXM1抑制滋养细胞增殖，与妊娠期合并子痫前期关系密切7。因此，推测miR-142-3p或可靶向调控FOXM1参与妊娠期高血压疾病的发生发展，为此，本研究分析妊娠期高血压患者血清FOXM1、miR-142-3p表达对不良妊娠结局的预测价值，以期为临床早诊断、早控制妊娠期高血压患者和降低不良妊娠结局提供理论参考。1资料和方法1.1一般资料选取2015年6月至2020年6月在本院接受治疗并分娩的681例妊娠期高血压疾病患者作为研究组，年龄2443岁，平均（33.304.68）岁；孕周（入院治疗时妊娠周期）3440周，平均（37.850.83）周。以同期在本院定期产检并分娩的700例正常妊娠者作为对照组，年龄 2240 岁，平均（33.695.47）岁；孕周3640 周，平均（37.921.10）周。本研究经医院伦理委员会审核批准院科伦审：（2015）伦审第（247）号后进行。