妊娠期肝内胆汁淤积症及无症状妊娠期高胆汁酸血症孕妇血清胆汁酸谱的特征及其诊断价值  

Characteristics and diagnostic value of serum bile acids profile in pregnant women with intrahepatic cholestasis of pregnancy and asymptomatic hypercholanemia of pregnancy

作　　者：缑灵山 尹馨 刘杰[2] 索峰[1] 吴昕雨 王真真 王巧莲[3] 董步连 顾茂胜 刘道彦[2] Gou Lingshan;Yin Xin;Liu Jie;Suo Feng;Wu Xinyu;Wang Zhenzhen;Wang Qiaolian;Dong Bulian;Gu Maosheng;Liu Daoyan(Center for Genetic Meidicine,Xuzhou Maternity and Child Health Care Hospital,Xuzhou 221009,China;Department of Clinical Laboratory,Xuzhou Maternity and Child Health Care Hospital,Xuzhou 221009,China;Department of Obstetrics,Xuzhou Maternity and Child Health Care Hospital,Xuzhou 221009,China)

机构地区：[1]徐州市妇幼保健院遗传医学中心,徐州221009 [2]徐州市妇幼保健院检验科,徐州221009 [3]徐州市妇幼保健院产科,徐州221009

出　　处：《中华妇产科杂志》2024年第4期270-278,共9页Chinese Journal of Obstetrics and Gynecology

基　　金：徐州市重点研发计划(KC22190);徐州市医学重点专科建设及人才培养(XWRCHT20220060);徐州市推动科技创新专项(KC21061)。

摘　　要：目的分析正常妊娠、妊娠期肝内胆汁淤积症(ICP)及无症状高胆汁酸血症(AHP)孕妇血清中的胆汁酸组分,评估血清胆汁酸谱在ICP和AHP诊断中的应用价值。方法收集2022年6月至2023年5月于徐州市妇幼保健院产前检查的122例孕妇的临床资料,其中正常妊娠组54例,ICP组28例,AHP组40例。采用超高效液相色谱-串联质谱技术检测各组孕妇血清中15种胆汁酸水平,包括胆酸(CA)、鹅脱氧胆酸(CDCA)、脱氧胆酸(DCA)、石胆酸(LCA)、熊脱氧胆酸(UDCA)、甘氨胆酸(GCA)、甘氨鹅脱氧胆酸(GCDCA)、甘氨脱氧胆酸(GDCA)、甘氨石胆酸(GLCA)、甘氨熊脱氧胆酸(GUDCA)、牛磺胆酸(TCA)、牛磺鹅脱氧胆酸(TCDCA)、牛磺脱氧胆酸(TDCA)、牛磺石胆酸(TLCA)和牛磺熊脱氧胆酸(TUDCA)。应用主成分分析(PCA)和正交偏最小二乘法判别分析(OPLS-DA)模型筛选差异胆汁酸,受试者工作特征(ROC)曲线分析组间差异胆汁酸及其联合指标的诊断效能。结果(1)与正常妊娠组比较,ICP组孕妇血清中LCA、GCA、GCDCA、GDCA、GLCA、UDCA、TCA、TCDCA、TDCA、TLCA、GUDCA及TUDCA水平的差异均有统计学意义(P均<0.05),AHP组孕妇血清中LCA、DCA、GCA、GCDCA、GDCA、GLCA、TCA、TCDCA、TDCA、TLCA、GUDCA及TUDCA水平的差异均有统计学意义(P均<0.05);与ICP组比较,AHP组孕妇血清中CDCA、DCA、UDCA、TDCA、GUDCA及TUDCA水平的差异均有统计学意义(P均<0.05)。(2)OPLS-DA模型中,ICP组与AHP组之间的差异胆汁酸为TUDCA、TCA、UDCA、GUDCA和GCA,其变量投影重要性(VIP)值分别为1.489、1.345、1.344、1.184和1.111;AHP组与正常妊娠组之间的差异胆汁酸为TCA、GCDCA、GCA、TDCA、GDCA和TCDCA,其VIP值分别为1.236、1.229、1.197、1.145、1.139和1.138。(3)ROC曲线分析结果显示,TUDCA、TCA、UDCA、GUDCA和GCA组成的联合指标对于ICP与AHP鉴别诊断的曲线下面积(AUC)为0.860,敏感度和特异度分别为67.9%、95.0%;TCA、GCDCA、GCA、TDCA、GDCA和TCDCA组成的联�Objective To analyze serum bile acid profiles in pregnant women with normal pregnancy,intrahepatic cholestasis of pregnancy(ICP)and asymptomatic hypercholanemia of pregnancy(AHP),and to evaluate the application value of serum bile acid profiles in the diagnosis of ICP and AHP.Methods The clinical data of 122 pregnant women who underwent prenatal examination in Xuzhou Maternal and Child Health Care Hospital from June 2022 to May 2023 were collected,including 54 cases of normal pregnancy group,28 cases of ICP group and 40 cases of AHP group.Ultraperformance liquid chromatography-tandem mass spectrometry was used to measure the levels of 15 serum bile acids in each group,including cholic acid(CA),chenodeoxycholic acid(CDCA),deoxycholic acid(DCA),lithocholic acid(LCA),ursodeoxycholic acid(UDCA),glycolcholic acid(GCA),glycochenodeoxycholic acid(GCDCA),glycodeoxycholic acid(GDCA),glycolithocholic acid(GLCA),glycoursodeoxycholic acid(GUDCA),taurocholic acid(TCA),taurochenodeoxycholic acid(TCDCA),taurodeoxycholic acid(TDCA),taurolithocholic acid(TLCA)and tauroursodeoxycholic acid(TUDCA).Principal component analysis(PCA)and orthogonal partial least squares discriminant analysis(OPLS-DA)were used to screen differential bile acids.The receiver operating characteristic(ROC)curve was used to analyze the diagnostic efficacy of differential bile acids and combined indicators between groups.Results(1)Compared with normal pregnancy group,the serum levels of LCA,GCA,GCDCA,GDCA,GLCA,UDCA,TCA,TCDCA,TDCA,TLCA,GUDCA and TUDCA in ICP group were significantly different(all P<0.05),while the levels of LCA,DCA,GCA,GCDCA,GDCA,GLCA,TCA,TCDCA,TDCA,TLCA,GUDCA and TUDCA in AHP group were significantly different(all P<0.05).Compared with ICP group,the serum levels of CDCA,DCA,UDCA,TDCA,GUDCA and TUDCA in AHP group were significantly different(all P<0.05).(2)In the OPLS-DA model,the differential bile acids between ICP group and AHP group were TUDCA,TCA,UDCA,GUDCA and GCA,and their variable importance in projection(VIP)were 1.489,1.345,1.344,1.18

关 键 词：妊娠并发症 胆汁淤积 肝内 胆汁酸类 串联质谱法 代谢疾病 

分 类 号：R714.255[医药卫生—妇产科学]