子痫前期患者血清miR-20b、miR-4443水平及与不良妊娠结局的关系

Serum levels of miR-20b and miR-4443 of patients with severe preeclampsia and their relationships with adverse pregnancy outcomes

摘要

目的 检测子痫前期(PE)患者血清微小RNA-20b(miR-20b)、微小RNA-4443(miR-4443)的水平,并探讨二者对PE患者妊娠结局的预测价值。方法 选取2021年2月至2023年1月在本院接受治疗的212名PE患者为研究组,根据病情严重程度分为重度PE组(n=106)和轻度PE组(n=106);另选取同期106例孕检健康的孕妇作为对照组.根据重度PE组患者的妊娠结局分为妊娠结局良好组和妊娠结局不良组.采用实时荧光定量PCR法(qRT-PCR)检测所有受试者血清中miR-20b和miR-4443的表达水平;使用多因素Logistic回归分析患者妊娠结局的影响因素;采用受试者工作特征(ROC)曲线评估miR-20b、miR-4443对重度PE孕妇妊娠不良结局的预测价值。结果 对照组、轻度PE组、重度PE组血清miR-20b、miR-4443水平逐渐升高(F值分别为486.199和354.434,P<0.001),胎儿宫内窘迫和早产的发生率在各组之间差异显著(χ²值为10.498和15.163,P<0.001).重度PE组不良妊娠结局总发生率为48.11%,显著高于轻度PE组及对照组(χ²=50.956,P<0.001).妊娠结局不良组miR-20b水平及miR-4443水平均显著高于妊娠结局良好组(t=5.750,5.853,P<0.001).多因素Logistic回归分析表明,miR-20b(OR=3.564,95%CI:1.546~8.214)、miR-4443(OR=2.365,95%CI:1.472~3.800)、收缩压(OR=2.869,95%CI:1.373~5.995)、尿蛋白(OR=3.837,95%CI:1.910~7.709)、甘油三酯(TG)(OR=4.236,95%CI:2.027~8.851)是患者发生不良妊娠结局的危险因素(P<0.05).ROC曲线分析结果显示,miR-20b、miR-4443联合预测重度PE妊娠结局的曲线下面积(AUC)为0.945(95%CI:0.901~0.989),显著高于miR-20b及miR-4443单独预测(Z值分别为2.412和2.055,P<0.05)。结论 重度PE患者血清miR-20b、miR-4443呈高表达,与不良妊娠结局的发生风险有关,二者联合使用可作为重度PE患者不良妊娠结局的预测指标.

Abstract

Objective To detect serum levels of microRNA-20b (miR-20b) and microRNA-4443 (miR-4443) of patients with severe preeclampsia, and to explore their predictive values for pregnancy outcomes of the patients. Methods A total of 106 patients with severe preeclampsia who were treated in our hospital from February 2021 to January 2023 were selected as severe preeclampsia group, and 106 patients with mild preeclampsia were selected as mild preeclampsia group, other 106 healthy pregnant women who received regular prenatal examination in the same period were as the control group. Quantitative real-time PCR (qRT-PCR) method was applied to detect expression levels of miR-20b and miR-4443 in serum. According to pregnancy outcome, the patients with preeclampsia were divided into good pregnancy outcome group (n=55) and poor pregnancy outcome group (n=51). Multivariate Logistic regression was applied to analyze influencing factors of pregnancy outcomes of the patients with severe preeclampsia. Receiver operating characteristic (ROC) curve was applied to evaluate values of miR-20b and miR-4443 in predicting adverse pregnancy outcomes of the patients with severe preeclampsia. Results The serum levels of miR-20b and miR-4443 of the pregnant women in the control group, mild preeclampsia group and severe preeclampsia group gradually increased (F=486.199 and 354.434 respectively, both P<0.001). There were significant differences in incidences of fetal intrauterine distress and preterm delivery (χ²=10.498 and 15.163 respectively, both P<0.001). The total incidence of adverse pregnancy outcomes in the severe preeclampsia group was 48.11%, which was significantly higher than those in the mild preeclampsia group and the control group (χ²=50.956, P<0.001). The serum levels of miR-20b and miR-4443 of the pregnant women in the poor pregnancy outcome group were significantly higher than those in the good pregnancy outcome group (t=5.750 and 5.853 respectively, both P<0.001). Multivariate Logistic regression analysis showed that miR-20b (OR=3.564, 95% CI: 1.546-8.214), miR-4443 (OR=2.365, 95% CI: 1.472-3.800), systolic blood pressure (OR=2.869, 95% CI: 1.373-5.995), urinary protein (OR=3.837, 95% CI: 1.910-7.709) and triglycerides (TG) (OR=4.236, 95% CI: 2.027-8.851) were all risk factors for adverse pregnancy outcomes of the patients with severe preeclampsia (all P<0.05). ROC curve analysis showed that area under the curve (AUC) of combination detection of serum miR-20b and miR-4443 levels for predicting pregnancy outcome of the patients with severe preeclampsia was 0.945 (95% CI: 0.901-0.989), which was significantly higher than those predicted by single detection of miR-20b (Z=2.412, P<0.05) and miR-4443 alone (Z=2.055, P<0.05). Conclusion The miR-20b and miR-4443 of the patients with severe preeclampsia are highly expressed in serum, which is related to risk of adverse pregnancy outcomes. The combination detection of serum miR-20b and miR-4443 levels can be considered as a predictive index for adverse pregnancy outcomes of the patients with severe preeclampsia.

关键词

子痫前期 / 微小RNA-20b / 微小RNA-4443 / 妊娠结局 / 预测

Key words

severe preeclampsia / microRNA-20b / microRNA-4443 / pregnancy outcome / prediction

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基金资助

2022年河北省医学科学研究课题计划项目(20221770)

2023年河北省医学科学研究课题计划项目(20231749)