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.
万方数据