孕中期血清氧化应激指标动态变化及其对妊娠期高血压疾病的预测价值

Dynamic changes of serum oxidative stress indexes in the second trimester of pregnancy and their predictive value for hypertensive disorders in pregnancy

摘要

目的 探索外周血氧化应激指标与妊娠期高血压疾病(HDP)的相关性。方法 选择2022年1月至2023年8月于沧州市人民医院建档、定期产前检查并确诊HDP的120例患者为研究对象,分为妊娠期高血压组(n=40)、子痫前期组(n=40)、重度子痫前期组(n=40);另外随机选取40位健康孕妇纳入对照组.采集孕早期、孕中期不同时期外周血,测定血清脂质活性氧(ROS)、超氧化物歧化酶(SOD)、人血红素氧合酶(HO-1)、谷胱甘肽过氧化物酶(GSH-PX)、丙二醛(MDA)水平,多因素Logistic回归分析这些指标与HDP疾病发生风险的关联性,构建并评价HDP风险列线图预测模型。结果 在孕8~13⁺⁶周的检查结果中,对照组、妊娠期高血压组、子痫前期组、重度子痫前期组血清SOD、GSH-PX水平均依次降低,差异有统计学意义(F值分别为29.838、7.955,P<0.05);妊娠期高血压组、子痫前期组、重度子痫前期组MDA水平依次升高,差异有统计学意义(F=21.931,P<0.05).孕14~20周指标中,妊娠期高血压、子痫前期和重度子痫前期患者的ROS、MDA水平依次升高,SOD、HO-1、GSH-PX水平依次降低,差异有统计学意义(F值介于33.679~133.145之间,P<0.05).与孕8~13⁺⁶周指标相比,孕14~20周HDP各分组ROS、MDA水平升高,SOD、HO-1水平降低(t值介于5.016~245.488之间,P<0.05);孕14~20周重度子痫前期组GSH-PX水平低于孕8~13⁺⁶周,差异有统计学意义(t=5.227,P<0.05).多因素Logistic回归模型显示孕14~20周的ROS、MDA是HDP发生的独立危险因素(OR值分别为1.917、1.818,P<0.05),SOD、HO-1、GSH-PX是独立保护因素(OR值分别为0.128、0.121、0.149,P<0.05);随着患者水平升高,氧化应激指标与HDP发生风险的关联效应也相应增加(P<0.05).本研究构建的列线图风险预测模型经过Bootstrap验证前后的受试者工作特征(ROC)曲线下面积分别为0.837(0.816~0.871)、0.864(0.835~0.894).校准曲线评价结果显示验证前后模型的预测值与实际值拟合良好。结论 孕14~20周的妊娠期高血压、子痫前期和重度子痫前期患者的ROS、MDA水平依次显著升高,SOD、HO-1、GSH-PX水平依次显著降低.利用超声指数与氧化应激指标共同构建的列线图预测模型准确度高、预测能力强.

Abstract

Objective To explore the correlation between peripheral blood oxidative stress markers and hypertensive disorders in pregnancy (HDP). Methods A total of 120 patients diagnosed with HDP between January 2022 and August 2023 at Cangzhou People's Hospital were selected for the study, divided into three groups: gestational hypertension group (n=40), preeclampsia group (n=40), and severe preeclampsia group (n=40). Additionally, 40 healthy pregnant women were randomly selected as the control group. Peripheral blood samples were collected during early and mid-pregnancy, and the levels of serum lipid reactive oxygen species (ROS), superoxide dismutase (SOD), heme oxygenase-1 (HO-1), glutathione peroxidase (GSH-PX), and malondialdehyde (MDA) were measured. Multivariate logistic regression analysis was performed to assess the association between these indicators and the risk of HDP, and a risk nomogram prediction model for HDP was constructed and evaluated. Results In the examination results at 8-13⁺⁶ weeks of pregnancy, the serum levels of SOD and GSH-PX were sequentially decreased in the control group, gestational hypertension group, preeclampsia group, and severe preeclampsia group, with statistically significant differences (F=29.838 and 7.955, respectively, P<0.05). The MDA levels in the gestational hypertension group, preeclampsia group, and severe preeclampsia group were sequentially increased, with a statistically significant difference (F=21.931, P<0.05). In the 14-20 week measurements, the ROS and MDA levels were sequentially increased in the gestational hypertension, preeclampsia, and severe preeclampsia groups, while the SOD, HO-1, and GSH-PX levels were sequentially decreased, with statistically significant differences (F values ranged from 33.679 to 133.145, P<0.05). Compared to the 8-13⁺⁶ week measurements, at 14-20 weeks, the ROS and MDA levels in HDP subgroups increased, while SOD and HO-1 levels decreased (t values ranged from 5.016 to 245.488, P<0.05). Additionally, the GSH-PX level in the severe preeclampsia group at 14-20 weeks was lower than that at 8-13⁺⁶ weeks, with a statistically significant difference (t=5.227, P<0.05). Multivariate logistic regression models showed that ROS and MDA at 14-20 weeks were independent risk factors for HDP (OR=1.917 and 1.818, respectively, P<0.05), while SOD, HO-1, and GSH-PX were independent protective factors (OR=0.128, 0.121, and 0.149, respectively, P<0.05). As the levels of oxidative stress markers increased, the association between these markers and the risk of HDP also increased (P<0.05). The nomogram risk prediction model constructed in this study showed an area under the receiver operating characteristic (ROC) curve of 0.837 (0.816-0.871) before Bootstrap validation and 0.864 (0.835-0.894) after validation. The calibration curve evaluation showed that the predicted values from the model were well-fitted with the actual values before and after validation. Conclusion In patients with gestational hypertension, preeclampsia, and severe preeclampsia at the 14-20 weeks of pregnancy, the levels of ROS and MDA were significantly increased, while the levels of SOD, HO-1, and GSH-PX were significantly decreased. The nomogram prediction model constructed using both ultrasound indices and oxidative stress markers demonstrated high accuracy and strong predictive ability.

关键词

氧化应激 / 妊娠期高血压疾病 / 脂质活性氧 / 不良妊娠结局 / 丙二醛

Key words

oxidative stress / hypertensive disorders of pregnancy / lipid reactive oxygen species / adverse pregnancy outcome / malondialdehyde

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基金资助

沧州市重点研发计划指导项目(222106052)