摘要目的：探讨肿瘤坏死因子相关凋亡诱导配体（TRAIL）与妊娠期高血压疾病（HDCP）的关联性；评估孕20周前TRAIL对HDCP发生的预测效率。方法采用巢式病例对照研究，收集2011年4月至2013年7月在广州医科大学附属广州市妇女儿童医疗中心产检和分娩的孕妇3000例。外周血血浆采自妊娠8～20周，病例追踪至分娩后。入选HDCP 孕妇73例、正常妊娠孕妇126名。采用蛋白抗体芯片技术检测20例HDCP孕妇和年龄孕周相匹配的20名正常孕妇的507个血浆蛋白的表达，应用DAVID软件和GO数据库对差异蛋白进行功能注释和富集分析。采用酶联免疫法检测53例HDCP孕妇和年龄孕周相匹配的106名正常孕妇的血浆TRAIL水平，结合62个临床高危因素调查数据，通过多因素Logistic回归分析，ROC曲线评价孕20周前TRAIL与HDCP发生的关联性和临床预测效率。结果从507个血浆蛋白中筛选出HDCP发病前表达差异蛋白23个。对表达显著下调的TRAIL进一步定量检测验证，表明孕20周前HDCP组TRAIL水平（45.7±13.1） pg／ml低于正常妊娠组（51.2±14.7） pg／ml，t＝2.334，P＝0.021。对该159例孕妇的多因素回归分析显示最后进入Logistic模型的3个因素分别为：贫血（ OR＝4.87，95％ CI：1.05～24.26）、孕前BMI （ OR＝1.72，95％CI：1.35～2.19）和TRAIL（OR＝0.96，95％ CI：0.92～0.99）。 Logistic模型的预测正确率为81.8％，AUC为0.81（95％CI：0.73～0.87，P＜0.05）。 HDCP孕妇组中TRAIL下调的独立预测意义：ROC曲线下面积0.59（95％CI：0.51～0.67，P＜0.05）。结论孕20周前HDCP组孕妇血浆中23个蛋白表达存在差异，证明HDCP是一组具有不同生物学改变的异质性疾病；TRAIL与HDCP发生具有关联性；孕20周前应用TRAIL联合传统高风险因素（贫血和孕前体重指数）预测HDCP发生有较高的临床应用价值。（中华检验医学杂志，2015，38：522-527）

abstractsObjective To assess the relationship between maternal plasma tumor necrosis factor-related apoptosis-inducing ligand ( TRAIL ) before 20 weeks′gestation and hypertensive disorder complicating pregnancy (HDCP);and to evaluate the predictive value of plasma TRAIL for HDCP.Methods A 2-phase screening/validation study was designed.In the screening phase , a nested, case-controlled study was performed , the plasma samples collected before 20 weeks′gestation from 20 women who later developed HDCP and 20 age-and gestation week-matched controls were tested in prospective screening test for protein expression profiling during pregnancy and HDCP.Plasma samples were analyzed by a human protein microarray technology designed to detect 507 proteins simultaneously.Differently expressed proteins′functional annotation and clustering were performed by using of Database for Annotation , Visualization and Integrated Discovery ( DAVID) and Gene Ontology ( GO) database.The TRAIL level of plasma samples obtained before 20 weeks′gestation from 53 women who later developed HDCP and 106 similarly matched controls were further validated by ELISA and 62 clinical risk factors were investigated.Logistic regression and ROC analysis were used to evaluate the relationship between TRAIL and HDCP and its predictive value for HDCP.Results In protein microarray analysis , 23 proteins expressed differently before 20 weeks′gestation between the two groups.Further validation results showed that TRAIL levels in HDCP patients were lower significantly (45.7 ±13.1) pg/ml than those in healthy pregnant controls (51.2 ±14.7)pg/ml, P=0.021.Multiple factor logistic regression analysis of 159 pregnancies showed that three features were finally entering the logistic model, they were:anemia (OR=4.87, 95% CI 1.05-24.26), pre-pregnancy BMI (OR=1.72, 95% CI 1.35 -2.19) and TRAIL (OR=0.96, 95% CI 0.92 -0.99).The predictive accuracy of logistic model was 81.8%.The model significantly increases the predictive value (AUC=0.81, 95%CI 0.73-0.87) compared to TRAIL as independent predictor (AUC=0.59, 95%CI 0.51-0.67).Conclusions Totally 23 proteins were expressed differentially before 20 weeks′gestation in plasma of women who later developed HDCP , confirming that HDCP is a heterogeneous disease with different biological changes.The data suggests that plasma TRAIL levels relate with the development of HDCP and its combination with pre-pregnancy BMI and anemia have a high predictive value for HDCP before 20 weeks′gestation.