血清游离胆汁酸 CA，LCA及胎盘 HIF-1α表达水平与 ICP患者不良妊娠结局的相关性研究

目的　探究血清游离胆汁酸胆酸（cholic acid, CA）、石胆酸 (litho cholic acid, LCA）以及胎盘组织缺氧诱导因子 -1α（hypoxia-inducible factor-1α, HIF-1α）表达水平与妊娠期肝内胆汁淤积症（intrahepatic cholestasis of pregnancy, ICP）患者不良妊娠结局间的关系。方法　选择 2020年 3月 ~2021年 4月于广东省东莞市第八人民医院就诊的妊娠期肝内胆汁淤积症患者 48例和无症状高胆汁酸血症（ asymptomatic hypercholanemia of pregnancy, AHP）70例作为研究对象，分别记为 ICP组和 AHP组。所有孕妇分娩前抽取静脉血用于检测肝功能指标 总胆汁酸（ TBA）、丙氨酸氨基转移酶（ALT）、天冬氨酸氨基转移酶（ AST）]以及胆汁酸亚型 （胆酸 (CA)、脱氧胆酸 (DCA)、鹅脱氧胆酸 (CDCA)、熊脱氧胆酸 UDCA)、石胆酸 (LCA)）]水平。产妇分娩后，记录两组产妇的妊娠结局，留取胎盘组织检测 HIF-1α的阳性表达率。比较 ICP产妇和 AHP产妇一般临床指标间的差异并探究影响产妇不良妊娠结局的独立相关因素。结果　ICP组和 AHP组产妇 TBA（46.54±6.58 μmol/L vs 47.21±6.38 μmol/L），ALT（38.26±5.37 U/L vs 36.58±5.72 U/L）， AST（28.48±3.54 U/L vs 28.92±3.85 U/L）组间差异无统计学意义（t=0.639~1.889, 均 P>0.05）；ICP组和 AHP组产妇 CA（3.78±0.63 μmol/L vs 1.24±0.56 μmol/L），LCA（7.86±0.54 μmol/L vs 1.13±0.17 μmol/L）组间差异有统计学意义（ t=26.100~113.936, P<0.001）。ICP组产妇 HIF-1α阳性表达率（ 68.75%）显著高于 AHP组（41.43%），差异有统计学意义（ χ2=12.359, P<0.05）。ICP组不良妊娠结局的发生率显著高于 AHP组（50.00% vs 28.57%），差异有统计学意义（ χ2=5.591, P=0.018）。TBA，CA，LCA以及 HIF-1α均是影响不良妊娠结局的独立相关因素（ Waldχ2=6.516,

Correlation between Serum Free Bile Acid CA,LCA and Placental HIF-1α Expression Levels and Adverse PregnancyOutcomes in Patients with ICP

Objective　To explore serum free bile acid (CA), lithocholic acid (LCA) and hypoxia inducible factor-1 (HIF-1) inplacenta α（ HIF-1 α）and investigate the relationship between the expression level and adverse pregnancy outcomes inpatients with intrahepatic cholestasis of pregnancy (ICP). Methods　48 patients with intrahepatic cholestasis of pregnancy (ICP)and 70 patients with asymptomatic hypercholanemia of pregnancy (AHP) from March 2020 to April 2021 were selected asobjects. Venous blood before delivery were collected to detect liver function total bile acid (TBA), alanine aminotransferase(ALT), aspartate aminotransferase (AST)] and the levels of bile acid subtypes cholic acid (CA), deoxycholic acid (DCA),chenodeoxycholic acid (CDCA), ursodeoxycholic acid (UDCA), lithocholic acid (LCA)]. After the parturients gave birth, thepregnancy outcomes of the two groups were recorded, and the placental tissues were collected to detect the rate of positiveexpression of hypoxia inducible factor-1α. The differences of general clinical indicators between two groups were conpared, andthe independent related factors that affect the adverse pregnancy outcomes of women were analysed. Results　There was asignificant difference between the two group(t=0.639~1.889, all P>0.05) of TBA (46.54±6.58 μmol/L vs 47.21±6.38 μmol/L),ALT (38.26±5.37 U/L vs 36.58±5.72 U/L) and AST (28.48±3.54 U/L vs 28.92±3.85 U/L) in the ICP group and AHP group ofmaternal. There was a significant difference between the two groups (t=26.100~113.936, all P<0.05) of CA (3.78±0.63 μmol/Lvs 1.24±0.56 μmol/L ), LCA (7.86±0.54 μmol/L vs 1.13±0.17 μmol/L) in ICP group and AHP group of maternal. Thepositive expression rate of HIF-1α in the ICP group (68.75%) was significantly higher than that of the AHP group（41.43%), thedifference was statistically significant（χ2=12.359，P<0.05）. The incidence of adverse pregnancy outcomes in the ICP groupwas significantly higher than that in the AHP group (50.00% vs 28.57%), the difference was statistically significant(χ2=5.591,P=0.018). CA,LCA and HIF-1α were independent factors that affect adverse pregnancy outcomes(Waldχ2=6.516, 7.215, 8.446,8.516, P=0.008, 0.038, 0.042, 0.016). Conclusion　Serum CA and LCA in ICP patients were significantly higher than those ofthe AHP. The high expression of HIF-1α was associated with the adverse pregnancy outcome of ICP.