妊娠期高血压疾病孕妇胎盘组织中HDAC8和SMAD4的表达及与妊娠结局的相关性

Expression of HDAC8 and SMAD4 in placental tissue of pregnant women with hypertensive disorder complicating pregnancy and the correlation with pregnancy outcomes

目的探讨妊娠期高血压疾病(HDCP)孕妇胎盘组织中组蛋白去乙酰化酶8(HDAC8)、果蝇母本抗生存因子蛋白同源物4(SMAD4)的表达与疾病严重程度及妊娠结局的相关性。方法选择2020年8月至2022年12月河北中石油中心医院收治的96例HDCP孕妇为观察对象(HDCP组),根据病情严重程度将其分为妊娠期高血压组35例,轻度子痫前期(PE)组33例,重度PE组28例;选择同期96例健康孕妇为对照组。根据妊娠结局,将HDCP孕妇分为妊娠结局良好组57例与妊娠结局不良组39例。以免疫组化法检测HDCP孕妇胎盘组织中HDAC8、SMAD4的表达水平,以实时荧光定量PCR(RT-qPCR)检测胎盘组织中HDAC8 mRNA、SMAD4 mRNA的表达水平;比较不同组别孕妇及不同妊娠结局孕妇胎盘组织中HDAC8、SMAD4的表达,以受试者工作特征(ROC)曲线分析HDAC8 mRNA、SMAD4 mRNA诊断HDCP孕妇发生不良妊娠结局的价值;采用多因素Logistic回归分析HDCP孕妇妊娠结局的影响因素。结果HDCP组与对照组胎盘组织中HDAC8、SMAD4的阳性表达率(χ^(2)值分别为30.561、40.776),以及HDAC8 mRNA、SMAD4 mRNA表达水平(t值分别为12.101、22.342)比较,差异均有统计学意义(P<0.05)。妊娠期高血压组、轻度PE组、重度PE组胎盘组织中HDAC8、SMAD4的阳性表达率(χ^(2)值分别为21.055、15.903),以及HDAC8 mRNA、SMAD4 mRNA表达水平(F值分别为48.158、21.879)比较,差异均有统计学意义(P<0.05)。HDCP组与对照组早产儿、胎儿生长受限、胎儿窘迫、新生儿窒息的发生率比较差异均有统计学意义(χ^(2)值分别为5.858、6.391、6.752、4.301,P<0.05)。妊娠结局良好组的收缩压、舒张压、24h尿蛋白及HDAC8 mRNA和SMAD4 mRNA表达水平比较,差异均有统计学意义(t值分别为2.770、5.058、3.062、7.282、6.031,P<0.05)。HDAC8 mRNA、SMAD4 mRNA及二者联合诊断HDCP孕妇发生不良妊娠结局的曲线下面积分别为0.780、0.779、0.918,二者联合诊断的曲线下面积明显高于单独诊断者(Z值分别为2.412、2.522,P<0.05)。收缩压(OR=2.895,95%CI:1.580~5.305)、舒张压(OR=2.342,95%CI:1.241~4.419)、SMAD4 mRNA(OR=2.765,95%CI:1.545~4.948)均是HDCP孕妇发生不良妊娠结局的独立危险因素(P<0.05),HDAC8 mRNA(OR=0.764,95%CI:0.638~0.915)是HDCP孕妇发生不良妊娠结局的保护因素(P<0.05)。结论HDCP孕妇胎盘组织中HDAC8表达降低,SMAD4表达升高;其与孕妇病情严重程度及不良妊娠结局有关,可能参与了HDCP的发生及发展。

Objective To investigate the correlation between the expression of histone deacetylase 8(HDAC8)and small mother against decapentaplegic(SMAD)in placental tissue of pregnant women with hypertensive disorder complicating pregnancy(HDCP)and the severity of disease and pregnancy outcomes.Methods A total of 96 pregnant women diagnosed with HDCP at Hebei PetroChina Central Hospital from August 2020 to December 2022 were selected as the observation group(HDCP group).Based on disease severity,they were divided into three subgroups:35 cases in the gestational hypertension group,33 cases in the mild preeclampsia(PE)group,and 28 cases in the severe PE group.Additionally,96 healthy pregnant women during the same period were selected as the control group.According to pregnancy outcomes,HDCP pregnant women were further divided into a good outcome group(57 cases)and a poor outcome group(39 cases).The expression levels of HDAC8 and SMAD4 in the placental tissue of HDCP pregnant women were detected using immunohistochemistry,while real-time quantitative PCR(RT-qPCR)was employed to assess the expression levels of HDAC8 mRNA and SMAD4 mRNA in placental tissue.The expression of HDAC8 and SMAD4 in different groups and different pregnancy outcome groups was compared.The diagnostic value of HDAC8 mRNA and SMAD4 mRNA for adverse pregnancy outcomes in HDCP pregnant women was analyzed using receiver operating characteristic(ROC)curves.Multivariable logistic regression was used to analyze the influencing factors of pregnancy outcomes in HDCP pregnant women.Results The positive expression rates of HDAC8 and SMAD4 in placental tissues of the HDCP group(χ^(2)=30.561 and 40.776,respectively,P<0.05)and the mRNA expression levels of HDAC8 and SMAD4(t=12.101 and 22.342,respectively,P<0.05)in the placental tissues of the HDCP group were significantly different from those of the control group.The positive expression rates of HDAC8 and SMAD4 in placental tissue among the gestational hypertension group,mild PE group,and severe PE group(χ^(2)=21.055 and 15.903,respectively,P<0.05),as well as the expression levels of HDAC8 mRNA and SMAD4 mRNA(F=48.158 and 21.879,respectively,P<0.05),also demonstrated statistically significant differences.The incidence rates of preterm birth,fetal growth restriction,fetal distress,and neonatal asphyxia in the HDCP group compared to the control group were statistically significant(χ^(2)=5.858,6.391,6.752,and 4.301,respectively,P<0.05).The systolic blood pressure,diastolic blood pressure,24h urine protein,and expression levels of HDAC8 mRNA and SMAD4 mRNA in the good pregnancy outcome group showed statistically significant differences(t=2.770,5.058,3.062,7.282 and 6.031,respectively,P<0.05).The area under the curve of HDAC8 mRNA,SMAD4 mRNA and the combined diagnosis of HDCP patients with adverse pregnancy outcomes were 0.780,0.779 and 0.918,respectively,and the area under the curve of the combined diagnosis of HDCP patients was significantly higher than that of patients diagnosed alone(Z=2.412 and 2.522,respectively,P<0.05).Systolic blood pressure(OR=2.895,95%CI:1.580-5.305),diastolic blood pressure(OR=2.342,95%CI:1.241-4.419),SMAD4 mRNA(OR=2.765,95%CI:1.545-4.948)was an independent risk factor for adverse pregnancy outcomes in HDCP patients(P<0.05),while HDAC8 mRNA was a protective factor(OR=0.764,95%CI:0.638-0.915,P<0.05).Conclusion The expression of HDAC8 is decreased,and SMAD4 is increased in the placental tissue of HDCP pregnant women.These expressions are associated with the severity of the mother's condition and adverse pregnancy outcomes,and they may be involved in the occurrence and development of HDCP.