血清HIF-1α、HO-1和sFlt-1对妊娠期肝内胆汁淤积症患者胎儿宫内缺氧的诊断价值OACSTPCD
Diagnostic value of serum HIF-1,HO-1 and sFlt-1 in fetal intrauterine hypoxia in patients with intrahepatic cholestasis of pregnancy
目的 探讨血清缺氧诱导因子1 α(HIF-1α)、血红素加氧酶-1(HO-1)和可溶性血管内皮生长因子受体-1(sFlt-1)对妊娠期肝内胆汁淤积症(ICP)患者胎儿宫内缺氧的诊断价值.方法 选择2020年1月至2022年12月在该院诊治的148例ICP患者纳入ICP组.选择同期该院66例健康孕妇纳入正常妊娠组.观察两组血清HIF-1α、HO-1和sFlt-1水平的变化,探讨宫内缺氧的影响因素,分析血清HIF-1α、HO-1和sFlt-1水平与ICP患者严重程度的关系,以及HIF-1α、HO-1和sFlt-1诊断ICP患者发生宫内缺氧的效能.根据ICP患者是否发生宫内缺氧分为宫内缺氧组和无宫内缺氧组,比较两组临床指标的差异.结果 ICP组血清HIF-1α和sFlt-1水平明显高于正常妊娠组(P<0.01),并且随着ICP疾病严重程度升高而升高(P<0.01),而血清HO-1水平明显低于正常妊娠组(P<0.01),随着ICP严重程度升高而降低(P<0.01).宫内缺氧组的直接胆红素、间接胆红素、总胆汁酸、甘胆酸、HIF-1α和sFlt-1水平明显高于无宫内缺氧组(P<0.01),凝血酶原时间、活化部分凝血活酶时间长于无宫内缺氧组(P<0.01),而血清HO-1水平明显低于无宫内缺氧组(P<0.01).多因素Logistic回归分析发现,直接胆红素、HIF-1α和sFlt-1水平升高,HO-1水平降低是宫内缺氧的独立危险因素(P<0.05).血清HIF-1α、HO-1和sFlt-1对ICP患者发生宫内缺氧具有较高的诊断效能,联合检测的灵敏度为96.8%,特异度为88.4%,曲线下面积(AUC)为0.969,明显高于单项指标HIF-1α(Z=3.294,P<0.001)、HO-1(Z=4.841,P<0.001)和 sFlt-1(Z=3.602,P<0.001)检测,而 3 项指标之间的 AUC 比较,差异无统计学意义(P>0.05).结论 HIF-1α、HO-1和sFlt-1是反映ICP患者严重程度和宫内缺氧的指标,三者联合检测有利于提高对胎儿宫内缺氧的诊断效能.
Objective To investigate the diagnostic value of serum hypoxia inducible factor 1α(HIF-1α),heme oxygenase-1(HO-1)and soluble vascular endothelial growth factor receptor-1(sFlt-1)levels for fetal intrauterine hypoxia in the patients with intrahepatic cholestasis of pregnancy(ICP).Methods A total of 148 ICP patients diagnosed and treated in this hospital from January 2020 to December 2022 were selected as the ICP group.Sixty-six normal pregnant women in this hospital during the same period were selected as the nor-mal pregnancy group.The changes of serum HIF-1α,HO-1 and sFlt-1 levels were observed in the two groups,the influencing factors of intrauterine hypoxia were investigated,and the relationship between serum HIF-1α,HO-1 and sFlt-1 levels with the severity in the patients with ICP was analyzed,as well as the efficiency of HIF-1α,HO-1 and sFlt-1 in diagnosing intrauterine hypoxia in ICP patients was analyzed.The ICP patients were divided into the intrauterine hypoxia group and non-intrauterine hypoxia group according to whether in-trauterine hypoxia occurred,and the differences of clinical indexes between the two groups were compared.Re-sults The serum HIF-1 and sFlt-1 levels in the ICP group were significantly higher than those in the normal pregnancy group(P<0.01),moreover which increased with the increase of ICP severity(P<0.01),while se-rum HO-1 level was significantly lower than that in the normal pregnancy group(P<0.01),and which de-creased with the increase of ICP severity(P<0.01).In the intrauterine hypoxia group,the direct bilirubin,in-direct bilirubin,total bile acid,glycocholic acid,HIF-1 and sFlt-1 levels were significantly higher than those in the non-intrauterine hypoxia group(P<0.01),while the prothrombin time and activated partial thromboplas-tin time were longer than those in the non-intrauterine hypoxia group(P<0.01),while the serum HO-1 level was significantly lower than that in the non-intrauterine hypoxia group(P<0.01).The multifactorial Logistic regression analysis showed that the increase of direct bilirubin,HIF-1α and sFlt-1 levels,and the decrease of HO-1 level were the independent risk factors for intrauterine hypoxia(P<0.05).The serum HIF-1,HO-1 and sFlt-1 levels for diagnosing intrauterine hypoxia in ICP patients had the higher diagnostic efficiency.The sensitivity and specificity of their combined detection were 96.8%and 88.4%respectively,and the area under the curve(AUC)was 0.969,which was significantly greater than that of single index HIF-1(Z=3.294,P<0.001),HO-1(Z=4.841,P<0.001)and sFlt-1(Z=3.602,P<0.001),while there was no statistically sig-nificant difference in AUC among the three indexes(P>0.05).Conclusion HIF-1,HO-1 and sFlt-1 are the indexes reflecting the severity degree and intrauterine hypoxia in the patients with ICP,and their combined de-tection is beneficial to improve the diagnostic efficiency of fetal intrauterine hypoxia.
陈芝逸;何雨婷;洪小丹
复旦大学附属妇产科医院产科,上海 200090
临床医学
缺氧诱导因子1α血红素加氧酶-1可溶性血管内皮生长因子受体-1妊娠期肝内胆汁淤积症宫内缺氧
hypoxia inducible factor 1αheme oxygenase-1soluble vascular endothelial growth factor receptor-1intrahepatic cholestasis of pregnancyintrauterine hypoxia
《检验医学与临床》 2024 (001)
39-44 / 6
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