摘要
目的 探讨转化生长因子β1(TGF-β1)/Smad信号通路在妊娠期高血压疾病(HDP)患者胎盘中的表达及临床意义.方法 回顾性选取2021年2月至2023年2月在新疆医科大学第六附属医院妇产科诊断为HDP的单胎孕妇100例,分为轻度组70例,重度组30例.另选正常单胎妊娠孕妇100名作为对照组.采用免疫组织化学链霉菌抗生物素蛋白-过氧化物酶连结(SP)法检测胎盘中TGF-β1、Smad2和Smad3的表达水平,并统计妊娠结局.利用多因素Logistic回归模型来分析TGF-β1/Smad信号通路主要蛋白与HDP以及不良妊娠结局的独立相关性;应用受试者工作特征(ROC)曲线分析TGF-β1/Smad信号通路主要蛋白对HDP的诊断价值以及对妊娠结局的预测价值.结果 重度组胎盘组织中 TGF-β1、Smad2 和 Smad3 的表达水平分别为(18.10±3.59)％、(4.69±1.01)％、(3.01±0.53)％,轻度组分别为(12.17±3.28)％、(3.16±0.74)％、(2.18±0.47)％,均高于对照组[(9.96±2.42)％、(2.47±0.68)％、(1.77±0.45)％],且重度组高于轻度组,差异均有统计学意义(P＜0.05).100例HDP患者中,妊娠结局良好者81例,妊娠结局不良者19例.妊娠结局不良者胎盘组织中TGF-β1、Smad2和Smad3的表达水平分别为(18.18±3.53)％、(4.77±1.02)％、(3.15±0.54)％,均高于妊娠结局良好者[(12.96±3.32)％、(3.35±0.69)％、(2.26±0.47)％],差异均有统计学意义(P＜0.05).Logistic回归分析显示,TGF-β1、Smad2和Smad3是导致HDP发生的独立危险因素(P＜0.05),也是HDP患者不良妊娠结局的独立危险因素(P＜0.05).ROC曲线分析显示,TGF-β1、Smad2、Smad2及三者联合诊断HDP的曲线下面积(AUC)分别为0.823、0.867、0.803、0.966,以三者联合诊断价值最高(敏感度为93.00％,特异度为88.00％);TGF-β1、Smad2、Smad3及三者联合预测HDP患者不良妊娠结局的AUC分别为0.846、0.934、0.820、0.974,以三者联合预测价值最高(敏感度为95.83％,特异度为90.70％).结论 TGF-β1/Smad信号通路参与了 HDP的发生与发展,TGF-β1、Smad2和Smad2对诊断HDP及预测HDP患者不良妊娠结局的价值较高,且随着病情的加重,TGF-β1、Smad2和Smad2逐渐升高.
Abstract
Objective To investigate the expression and clinical significance of transforming growth factor-β1(TGF-β1)/Smad signa-ling pathway in placenta of patients with hypertensive disorder of pregnancy(HDP).Methods A total of 100 singleton pregnant women diag-nosed with HDP in the Department of Obstetrics and Gynecology,the Sixth Affiliated Hospital of Xinjiang Medical University from February 2021 to February 2023 were selected and divided into the mild group(70 cases)and the severe group(30 cases).Another 100 normal singleton preg-nant women were selected as the control group.The expression levels of TGF-β1,Smad2 and Smad3 in placenta were detected by immunohisto-chemical streptavidin perosidase(SP)method,and the pregnancy outcome was counted.Multivariate Logistic regression model was used to analyze the independent correlation between the main proteins of TGF-β1/Smad signaling pathway and HDP and adverse pregnancy outcomes.The re-ceiver operating characteristic(ROC)curve was used to analyze the diagnostic value of the main proteins of TGF-β1/Smad signaling pathway for HDP and the predictive value for pregnancy outcome.Results The expression levels of TGF-β1,Smad2,and Smad3 in the placental tissue of the severe group were(18.10±3.59)％,(4.69±1.01)％,and(3.01±0.53)％,respectively,those of the mild group were(12.17±3.28)％,(3.16±0.74)％,and(2.18±0.47)％,respectively,which were higher than those of the control group[(9.96±2.42)％,(2.47±0.68)％,and(1.77±0.45)％)],and the severe group was higher than the mild group,the differences were statistically significant(P＜0.05).Among the 100 patients with HDP,81 had good pregnancy outcomes and 19 had poor pregnancy outcomes.The expression levels of TGF-β1,Smad2 and Smad3 in placental tissue of poor pregnancy outcome group were(18.18±3.53)％,(4.77±1.02)％,(3.15±0.54)％,respectively,which were higher than those of good pregnancy outcome group[(12.96±3.32)％,(3.35±0.69)％,(2.26±0.47)％],the differences were statis-tically significant(P＜0.05).Logistic regression analysis showed that TGF-β1,Smad2 and Smad3 were independent risk factors for HDP(P＜0.05),and also independent risk factors for adverse pregnancy outcomes in patients with HDP(P＜0.05).ROC curve analysis showed that the area under curve(AUC)of TGF-β1,Smad2,Smad2 and their combination in the diagnosis of HDP were 0.823,0.867,0.803 and 0.966,respectively.The combined diagnostic value of the three was the highest(sensitivity was 93.00％,specificity was 88.00％).The AUC of TGF-β1,Smad2,Smad3 and their combined prediction of adverse pregnancy outcomes in HDP patients were 0.846,0.934,0.820 and 0.974,respec-tively.The combined prediction value of the three was the highest(sensitivity was 95.83％,specificity was 90.70％).Conclusion TGF-β1/Smad signaling pathway is involved in the occurrence and development of HDP.TGF-β1,Smad2 and Smad2 have high value in the diagnosis of HDP and prediction of adverse pregnancy outcomes in patients with HDP.With the aggravation of the disease,TGF-β1,Smad2 and Smad2 grad-ually increase.
基金项目
新疆维吾尔自治区自然科学基金面上项目(2021D01C452)
维普
万方数据