子痫前期孕妇血清hTERT和Sirt6水平表达与疾病严重程度及妊娠结局评估中的价值研究

Study on the Serum hTERT and Sirt6 Level Expression and the Evaluation Value of Disease Severity and Pregnancy Outcome in Preeclampsia Pregnant Women

目的检测子痫前期孕妇血清中人端粒酶反转录酶(human telomerase reverse transcriptase,hTERT)、沉默信息调节因子6(silent information regulator 6,Sirt6)表达,并探究hTERT,Sirt6水平表达与疾病严重程度及妊娠结局评估中的价值。方法选取2018年1月~2022年12月在陕西省人民医院进行诊治的300例子痫前期孕妇作为子痫前期组,孕妇均符合《妊娠期高血压疾病诊治指南(2015)》中子痫前期诊断标准,选取同时期孕检的300例健康孕妇为对照组,根据病情严重程度将子痫前期组分为轻症子痫前期组(n=180)和重症子痫前期组(n=120),根据是否发生不良妊娠结局将子痫前期组分为正常妊娠组(n=165)和不良妊娠组(n=135)。酶联免疫吸附实验(enzyme-linked immunosorbnent assay,ELISA)法检测血清中hTERT和Sirt6水平,Spearman相关性分析血清中hTERT和Sirt6水平与子痫前期孕妇病情严重程度的相关性,利用受试者工作特征(receiver operating characteristic,ROC)曲线评估血清hTERT和Sirt6水平在子痫前期诊断及妊娠结局预测中的价值。结果与对照组比较,子痫前期组血清hTERT(22.15±5.82 ng/ml vs 30.12±9.56 ng/ml),Sirt6(5.26±1.62 ng/ml vs 7.06±2.29 ng/ml)水平降低,差异具有统计学意义(t=12.334,11.114,均P<0.001)。与轻症子痫前期组比较,重症子痫前期组孕妇血清hTERT(18.28±4.11 ng/ml vs 24.73±6.96 ng/ml),Sirt6(4.03±1.17 ng/ml vs 6.08±1.92 ng/ml)水平降低,差异具有统计学意义(t=9.142,10.469,均P<0.001)。与正常妊娠组比较,不良妊娠组子痫前期孕妇血清中hTERT(17.75±4.61 ng/ml vs 25.75±6.81 ng/ml),Sirt6(4.06±0.96 ng/ml vs 6.24±2.16 ng/ml)水平降低,差异具有统计学意义(t=11.639,10.878,均P<0.001)。Spearman相关性分析显示,血清hTERT,Sirt6水平与子痫前期孕妇疾病严重程度均呈负相关(r=-0.562,-0.604,均P<0.001)。ROC曲线分析结果显示,血清hTERT,Sirt6诊断子痫前期的曲线下面积(95%置信区间)[AUC(95%CI)]分别为0.711(0.673~0.747),0.727(0.689~0.762),两者联合诊断子痫前期的AUC(95%CI)为0.788(0.753~0.820),高于两者单独诊断(Z=2.719,2.154,P=0.007,0.031);血清hTERT,Sirt6预测子痫前期不良妊娠结局的AUC(95%CI)分别为0.786(0.735~0.831),0.783(0.732~0.829),两者联合预测子痫前期不良妊娠结局的AUC(95%CI)为0.849(0.804~0.888),高于两者单独预测(Z=1.855,1.861,P=0.032,0.031)。结论hTERT和Sirt6在子痫前期孕妇血清中水平较低,与子痫前期孕妇疾病严重程度均呈负相关,并对妊娠结局具有一定的评估价值。

Objective To detect the expression of human telomerase reverse transcriptase(hTERT)and silent information regulatory factor 6(Sirt6)in serum of pregnant women with preeclampsia,and explore the value of hTERT and Sirt6 levels in the evaluation of disease severity and pregnancy outcome.Methods A total of 300 patients with preeclampsia who were treated in Shaanxi Provincial People’s Hospital from January 2018 to December 2022 were selected as the preeclampsia group,and all pregnant women met the diagnostic criteria for preeclampsia in the Guidelines for the Diagnosis and Treatment of Hypertensive Disorders in Pregnancy(2015).Meanwhile,300 healthy pregnant women who underwent pregnancy examinations in Shaanxi Provincial People’s Hospital during the same period were selected as the control group.Preeclampsia group was divided into mild preeclampsia group(n=180)and severe preeclampsia group(n=120)according to the severity of the disease.The preeclampsia group was divided into normal pregnancy group(n=165)and adverse pregnancy group(n=135)according to the occurrence of adverse pregnancy outcomes.Serum hTERT and Sirt6 levels were detected by enzyme-linked immunosorbent assay(ELISA).Spearman correlation analysis was applied to analyze the correlation between serum hTERT and Sirt6 levels and the severity of preeclampsia in patients.Receiver operating characteristic(ROC)curve was applied to evaluate the value of serum hTERT and Sirt6 levels in the diagnosis of preeclampsia and prediction of pregnancy outcomes.Results Compared with the control group serum levels of hTERT(22.15±5.82 ng/ml vs 30.12±9.56 ng/ml)and Sirt6(5.26±1.62 ng/ml vs 7.06±2.29 ng/ml)in preeclampsia group were decreased,and the differences were significant(t=12.334,11.114,all P<0.001).Compared with the mild preeclampsia group,the serum levels of hTERT(18.28±4.11 ng/ml vs 24.73±6.96 ng/ml)and Sirt6(4.03±1.17 ng/ml vs 6.08±1.92 ng/ml)in the severe preeclampsia group were decreased,and the differences were significant(t=9.142,10.469,all P<0.001).Compared with the normal pregnancy group,the serum levels of hTERT(17.75±4.61 ng/ml vs 25.75±6.81 ng/ml)and Sirt6(4.06±0.96 ng/ml vs 6.24±2.16 ng/ml)of preeclampsia pregnant women in the adverse pregnancy group were decreased,and the differences were significant(t=11.639,10.878,all P<0.001).Spearman correlation analysis showed that the levels of hTERT and Sirt6 in serum were negatively correlated with the severity of preeclampsia in patients(r=-0.562,-0.604,all P<0.001).ROC curve analysis results showed that the area under the curve(95%confidence interval)[AUC(95%CI)]of serum hTERT and Sirt6 in the diagnosis of preeclampsia were 0.711(0.673~0.747)and 0.727(0.689~0.762),respectively.The AUC(95%CI)of the combined diagnosis of preeclampsia was 0.788(0.753~0.820),which was higher than that of the combined diagnosis of preeclampsia(Z=2.719,2.154,P=0.007,0.031).The AUC of serum hTERT and Sirt6 for predicting adverse pregnancy outcomes of preeclampsia were 0.786(0.735~0.831)and 0.783(0.732~0.829),respectively.The AUC(95%CI)of serum HTERT and Sirt6 for predicting adverse pregnancy outcomes of preeclampsia was 0.849(0.804~0.888).It was higher than predicted by the two alone(Z=1.855,1.861,P=0.032,0.031).Conclusion The serum levels of hTERT and Sirt6 in pregnant women with preeclampsia were low,and they were negatively correlated with the disease severity of preeclampsia patients.They may have certain evaluation values for pregnancy outcomes.