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

Correlation between Serum Free Bile Acid CA,LCA and Placental HIF-1αExpression Levels and Adverse Pregnancy Outcomes in Patients with ICP

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±6.58μmol/L vs 47.21±6.38μmol/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±0.63μmol/L vs 1.24±0.56μmol/L),LCA(7.86±0.54μmol/L vs 1.13±0.17μmol/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(χ^(2)=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(χ^(2)=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(Waldχ^(2)=6.516,7.215,8.446,8.516,P=0.008,0.038,0.042,0.016)。结论ICP产妇血清CA,LCA显著高于AHP组,HIF-1α高表达与ICP不良妊娠结局间存在显著的相关性。

Objective To explore serum free bile acid(CA),lithocholic acid(LCA)and hypoxia inducible factor-1(HIF-1)in placentaα(HIF-1α)and investigate the relationship between the expression level and adverse pregnancy outcomes in patients 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 as objects.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,the pregnancy outcomes of the two groups were recorded,and the placental tissues were collected to detect the rate of positive expression of hypoxia inducible factor-1α.The differences of general clinical indicators between two groups were conpared,and the independent related factors that affect the adverse pregnancy outcomes of women were analysed.Results There was a significant difference between the two group(t=0.639~1.889,all P>0.05)of TBA(46.54±6.58μmol/L vs 47.21±6.38μmol/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 of maternal.There was a significant difference between the two groups(t=26.100~113.936,all P<0.05)of CA(3.78±0.63μmol/L vs 1.24±0.56μmol/L),LCA(7.86±0.54μmol/L vs 1.13±0.17μmol/L)in ICP group and AHP group of maternal.The positive expression rate of HIF-1αin the ICP group(68.75%)was significantly higher than that of the AHP group(41.43%),the difference was statistically significant(χ^(2)=12.359,P<0.05).The incidence of adverse pregnancy outcomes in the ICP group was significantly higher than that in the AHP group(50.00%vs 28.57%),the difference was statistically significant(χ^(2)=5.591,P=0.018).CA,LCA and HIF-1αwere independent factors that affect adverse pregnancy outcomes(Waldχ^(2)=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 of the AHP.The high expression of HIF-1αwas associated with the adverse pregnancy outcome of ICP.