中华检验医学杂志
中華檢驗醫學雜誌
중화검험의학잡지
CHINESE JOURNAL OF LABORATORY MEDICINE
2015年
8期
522-527
,共6页
周成%杨红玲%曾芳玲%江敏%吴娟
週成%楊紅玲%曾芳玲%江敏%吳娟
주성%양홍령%증방령%강민%오연
高血压,妊娠性%受体, TNF相关凋亡诱导配体%蛋白质阵列分析
高血壓,妊娠性%受體, TNF相關凋亡誘導配體%蛋白質陣列分析
고혈압,임신성%수체, TNF상관조망유도배체%단백질진렬분석
Hypertension,pregnancy-induced%Receptors,TNF-related apoptosis-inducing ligand%Protein array analysis
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）
目的：探討腫瘤壞死因子相關凋亡誘導配體（TRAIL）與妊娠期高血壓疾病（HDCP）的關聯性；評估孕20週前TRAIL對HDCP髮生的預測效率。方法採用巢式病例對照研究，收集2011年4月至2013年7月在廣州醫科大學附屬廣州市婦女兒童醫療中心產檢和分娩的孕婦3000例。外週血血漿採自妊娠8～20週，病例追蹤至分娩後。入選HDCP 孕婦73例、正常妊娠孕婦126名。採用蛋白抗體芯片技術檢測20例HDCP孕婦和年齡孕週相匹配的20名正常孕婦的507箇血漿蛋白的錶達，應用DAVID軟件和GO數據庫對差異蛋白進行功能註釋和富集分析。採用酶聯免疫法檢測53例HDCP孕婦和年齡孕週相匹配的106名正常孕婦的血漿TRAIL水平，結閤62箇臨床高危因素調查數據，通過多因素Logistic迴歸分析，ROC麯線評價孕20週前TRAIL與HDCP髮生的關聯性和臨床預測效率。結果從507箇血漿蛋白中篩選齣HDCP髮病前錶達差異蛋白23箇。對錶達顯著下調的TRAIL進一步定量檢測驗證，錶明孕20週前HDCP組TRAIL水平（45.7±13.1） pg／ml低于正常妊娠組（51.2±14.7） pg／ml，t＝2.334，P＝0.021。對該159例孕婦的多因素迴歸分析顯示最後進入Logistic模型的3箇因素分彆為：貧血（ 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模型的預測正確率為81.8％，AUC為0.81（95％CI：0.73～0.87，P＜0.05）。 HDCP孕婦組中TRAIL下調的獨立預測意義：ROC麯線下麵積0.59（95％CI：0.51～0.67，P＜0.05）。結論孕20週前HDCP組孕婦血漿中23箇蛋白錶達存在差異，證明HDCP是一組具有不同生物學改變的異質性疾病；TRAIL與HDCP髮生具有關聯性；孕20週前應用TRAIL聯閤傳統高風險因素（貧血和孕前體重指數）預測HDCP髮生有較高的臨床應用價值。（中華檢驗醫學雜誌，2015，38：522-527）
목적：탐토종류배사인자상관조망유도배체（TRAIL）여임신기고혈압질병（HDCP）적관련성；평고잉20주전TRAIL대HDCP발생적예측효솔。방법채용소식병례대조연구，수집2011년4월지2013년7월재엄주의과대학부속엄주시부녀인동의료중심산검화분면적잉부3000례。외주혈혈장채자임신8～20주，병례추종지분면후。입선HDCP 잉부73례、정상임신잉부126명。채용단백항체심편기술검측20례HDCP잉부화년령잉주상필배적20명정상잉부적507개혈장단백적표체，응용DAVID연건화GO수거고대차이단백진행공능주석화부집분석。채용매련면역법검측53례HDCP잉부화년령잉주상필배적106명정상잉부적혈장TRAIL수평，결합62개림상고위인소조사수거，통과다인소Logistic회귀분석，ROC곡선평개잉20주전TRAIL여HDCP발생적관련성화림상예측효솔。결과종507개혈장단백중사선출HDCP발병전표체차이단백23개。대표체현저하조적TRAIL진일보정량검측험증，표명잉20주전HDCP조TRAIL수평（45.7±13.1） pg／ml저우정상임신조（51.2±14.7） pg／ml，t＝2.334，P＝0.021。대해159례잉부적다인소회귀분석현시최후진입Logistic모형적3개인소분별위：빈혈（ OR＝4.87，95％ CI：1.05～24.26）、잉전BMI （ OR＝1.72，95％CI：1.35～2.19）화TRAIL（OR＝0.96，95％ CI：0.92～0.99）。 Logistic모형적예측정학솔위81.8％，AUC위0.81（95％CI：0.73～0.87，P＜0.05）。 HDCP잉부조중TRAIL하조적독립예측의의：ROC곡선하면적0.59（95％CI：0.51～0.67，P＜0.05）。결론잉20주전HDCP조잉부혈장중23개단백표체존재차이，증명HDCP시일조구유불동생물학개변적이질성질병；TRAIL여HDCP발생구유관련성；잉20주전응용TRAIL연합전통고풍험인소（빈혈화잉전체중지수）예측HDCP발생유교고적림상응용개치。（중화검험의학잡지，2015，38：522-527）
Objective 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.
