子痫前期患者血清lncRNA HIF1A-AS1,CXCL9水平表达与病情程度及不良妊娠结局的关系分析

Analysis of Relationship between Serum lncRNA HIF1A-AS1,CXCL9 and Disease Severity,Adverse Pregnancy Outcomes in Patients with Preeclampsia

目的探讨子痫前期(Preeclanpsia)患者血清长链非编码RNA缺氧诱导因子-1α-反义链1(lncRNA HIF1A-AS1)、CXC趋化因子配体9(CXCL9)表达与病情程度及不良妊娠结局的关系。方法以2021年1月~2022年12月西安高新医院收治的83例子痫前期患者为子痫前期组,根据确诊时间对子痫前期患者进行分组,分为早发型子痫前期组(n=39)和晚发型子痫前期组(n=44);根据病情严重程度将子痫前期患者分为轻度子痫前期组(n=51)和重度子痫前期组(n=32);根据妊娠结局分为正常妊娠结局组(n=56)和不良妊娠结局组(n=27)。收集同期的60例健康妊娠孕妇为对照组。采用实时荧光定量PCR(qRT-PCR)检测血清lncRNA HIF1A-AS1相对表达量,酶联免疫吸附法(ELISA)检测血清CXCL9水平。Spearman秩相关分析血清lncRNA HIF1A-AS1,CXCL9与病情程度的相关性,Logistic回归分析子痫前期患者不良妊娠结局影响因素,绘制受试者工作特征(ROC)曲线评估血清lncRNA HIF1A-AS1,CXCL9对不良妊娠结局预测价值。结果子痫前期组血清lncRNA HIF1A-AS1相对表达量(0.73±0.26)低于对照组(1.15±0.34),CXCL9水平(209.34±45.34 pg/ml)高于对照组(116.80±37.76 pg/ml),差异具有统计学意义(t=8.379,12.903,均P<0.05)。早发型子痫前期组血清lncRNA HIF1A-AS1相对表达量(0.58±0.21)低于晚发型子痫前期组(0.86±0.27),CXCL9水平(236.60±31.02 pg/ml)高于对照组(185.18±23.63 pg/ml),差异具有统计学意义(t=5.226,8.551,均P<0.05)。重度子痫前期组血清lncRNA HIF1A-AS1相对表达量(0.52±0.21)低于轻度子痫前期组(0.97±0.34),血清CXCL9水平(253.38±41.20 pg/ml)高于轻度子痫前期组(159.65±40.79 pg/ml),差异具有统计学意义(t=6.409,10.152,均P<0.05)。血清lncRNA HIF1A-AS1,CXCL9与子痫前期病情具有相关性(r=-0.627,0.651,均P<0.05)。CXCL9[OR(95%CI):1.581(1.098~2.276)]是子痫前期不良妊娠结局独立危险因素(P<0.05),lncRNA HIF1A-AS1[OR(95%CI):0.806(0.673~0.965)]是保护因素(P<0.05);早发型子痫前期[OR(95%CI):1.390(1.088~1.775)]和重度子痫前期[OR(95%CI):1.589(1.222~2.066)]是不良妊娠结局危险因素(均P<0.05)。血清lncRNA HIF1A-AS1,CXCL9及指标联合预测子痫前期不良妊娠结局的AUC分别为0.770,0.767和0.876,指标联合预测价值优于单一指标,差异具有统计学意义(Z=2.455,2.398,均P<0.05)。结论子痫前期患者血清lncRNA HIF1A-AS1表达下调,CXCL9表达上调,两指标与病情严重程度及不良妊娠结局有关,早期联合检测有望成为预测子痫前期患者不良妊娠结局的标志物。

Objective To explore the relationship between serum long non-coding RNA hypoxia-inducible factor 1 alpha antisense RNA 1(lncRNA HIFA1-AS1),CXC chemokine ligand 9(CXCL9)and disease severity,adverse pregnancy outcome in patients with preeclampsia.Methods A total of 83 patients with preeclampsia admitted to Xi'an Gaoxin Hospital January 2021 to December 2022 were taken as preeclampsia group,According to the time of diagnosis,patients with preeclampsia were divided into early onset preeclampsia group(n=39)and late onset preeclampsia group(n=44).According to the severity of the condition,patients with preeclampsia were divided into two groups:mild preeclampsia group(n=51)and severe preeclampsia group(n=32).According to pregnancy outcomes,they were divided into a normal pregnancy outcome group(n=56)and an adverse pregnancy outcome group(n=27).At the same time,60 healthy pregnant women with pregnancy were collected as control group.Real-timefluorescence quantitative PC(qRT-PCR)was used to detect serum lncRNA HIF1A-AS1,and enzyme-linked immunosorbent assay(ELISA)was used to detect serum CXCL9.Spearman rank correlation analysis was used to analyze the association between serum lncRNA HIF1A-AS1,CXCL9 and severity of disease.Logistic regression analysis was used to analyze the factors influencing the adverse pregnancy outcome in patients with preeclampsia.ROC curve was drawn to assess the predictive value of serum lncRNA HIF1A-AS1,CXCL9 for adverse pregnancy outcome.Results The relative expression of serum lncRNA HIF1A-AS1(0.73±0.26)in preeclampsia group was lower than that(1.15±0.34)in control group,and CXCL9 level(209.34±45.34 pg/ml)higher than that(116.80±37.76 pg/ml)in control group,the differences were statistically significant(t=8.379,12.903,all P<0.05).The relative expression of serum lncRNA HIF1A-AS1(0.58±0.21)in early-onset preeclampsia group was lower than that in late-onset preeclampsia group(0.86±0.27),and CXCL9 level(236.60±31.02 pg/ml)higher than that in late-onset preeclampsia group(185.18±23.63 pg/ml),the differences were statistically significant(t=5.226,8.551,all P<0.05).The relative expression of serum lncRNA HIF1A-AS1(0.52±0.21)in severe preeclampsia group was lower than that in late-onset preeclampsia group(0.97±0.34),and CXCL9 level(253.38±41.20 pg/ml)higher than that in late-onset preeclampsia group(159.65±40.79 pg/ml),the differences were statistically significant(t=6.409,10.152,all P<0.05).Serum lncRNA HIF1A-AS1 and CXCL9 were associated with condition of preeclampsia(r=-0.627,0.651,all P<0.05).CXCL9[OR(95%CI):1.581(1.098~2.276)]was independent risk factor for adverse pregnancy outcome in patients with preeclampsia(P<0.05).LncRNA HIF1A-AS1[OR(95%CI):0.806(0.673~0.965)]was a protective factor(P<0.05),and early-onset preeclampsia[OR(95%CI):1.390(1.088~1.775)]and severe preeclampsia[OR(95%CI):1.589(1.222~2.066)]were risk factors for adverse pregnancy outcome(all P<0.05).Serum lncRNA HIF1A-AS1,CXCL9 and indicators combined had predictive value for adverse pregnancy outcome in patients with preeclampsia,with AUC of 0.770,0.767 and 0.876,respectively.And the combined prediction AUC was better than single indicator,and differences were statistically significant(Z=2.455,2.398,all P<0.05).Conclusion Serum lncRNA HIF1A-AS1 expression is down-regulated and CXCL9 expression is up-regulated in patients with preeclampsia,both indicators are associated with severity of disease and adverse pregnancy outcome.Early detection of two indicators are expected to be markers for predicting adverse pregnancy outcome in patients with preeclampsia.