Department of Obstetrics and Gynecology, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Suzhou, Jiangsu, China (mainland).
Department of Obstetrics and Gynecology, Shenzhen Maternity and Child Healthcare Hospital Affiliated with Southern Medical University, Shenzhen, Guangdong, China (mainland).
Med Sci Monit. 2021 Apr 13;27:e930176. doi: 10.12659/MSM.930176.
BACKGROUND Intrahepatic cholestasis of pregnancy (ICP) is a condition specific to pregnancy, leading to increased fetal morbidity and mortality. Nitric oxide synthase (iNOS) may be a factor regulating the vasodilation of blood vessels, which are relevant to ischemic-hypoxic conditions. We aimed to explore the potential relationship between iNOS and ICP. MATERIAL AND METHODS A prospective, case-control study was conducted including 77 pregnant women with ICP and 80 healthy pregnant women as controls. Enzyme-linked immunosorbent assays were used to investigate maternal plasma iNOS levels. The placenta mRNA levels and cell-specific localization of iNOS were determined by quantitative polymerase chain reaction, western blotting, and immunohistochemical analysis. A multivariate linear regression model was used to identify the independent factors of serum total biliary acids (TAB) in ICP. RESULTS Compared with controls, the expression of iNOS was significantly lower in maternal serum and placentas with ICP (P<0.001). Maternal plasm iNOS levels were negatively correlated with TAB (r=-0.450, P<0.001), cholyglycine (r=-0.367, P<0.001), alanine aminotransferase (r=-.359, P<0.001), and aspartate aminotransferase (r=-0.329, P<0.001). iNOS level was an indicator for ICP by multivariate linear regression analysis (ß=-0.505, P<0.001). The ROC curve indicated the optimal cut-off level for iNOS was 2865.43 pg/mL (sensitivity, 85.71%; specificity, 63.75%). The ROC curve area for iNOS was 0.793 (95% CI 0.722-0.864). CONCLUSIONS iNOS plays an important role in poor fetoplacental vascular perfusion and adverse pregnancy outcomes. iNOS can provide complementary information in predicting the extent and severity of ICP.
妊娠肝内胆汁淤积症（ICP）是一种特定于妊娠的病症，可导致胎儿发病率和死亡率增加。一氧化氮合酶（iNOS）可能是调节血管舒张的因素，这与缺血缺氧条件有关。我们旨在探讨 iNOS 与 ICP 之间的潜在关系。
采用前瞻性病例对照研究，纳入 77 例 ICP 孕妇和 80 例健康孕妇作为对照。采用酶联免疫吸附法检测母血浆 iNOS 水平。通过定量聚合酶链反应、western blot 和免疫组织化学分析检测胎盘 mRNA 水平和 iNOS 的细胞特异性定位。采用多元线性回归模型确定 ICP 中血清总胆汁酸（TAB）的独立因素。
与对照组相比，ICP 孕妇母血和胎盘中 iNOS 的表达显著降低（P<0.001）。母血浆 iNOS 水平与 TAB（r=-0.450，P<0.001）、胆酰甘氨酸（r=-0.367，P<0.001）、丙氨酸氨基转移酶（r=-.359，P<0.001）和天冬氨酸氨基转移酶（r=-0.329，P<0.001）呈负相关。多元线性回归分析显示，iNOS 水平是 ICP 的指标（β=-0.505，P<0.001）。ROC 曲线表明，iNOS 的最佳截断值为 2865.43 pg/mL（灵敏度，85.71%；特异性，63.75%）。iNOS 的 ROC 曲线下面积为 0.793（95%CI 0.722-0.864）。
iNOS 在不良胎儿胎盘血管灌注和不良妊娠结局中发挥重要作用。iNOS 可以提供补充信息，预测 ICP 的程度和严重程度。
