Department of Gynecology and Obstetrics, Wuxi Maternal and Child Health Hospital, the Affiliated Hospital of Nanjing Medical University, Wuxi, Jiangsu, China ; Department of Pharmacology, College of Pharmaceutical Sciences, Soochow University, Suzhou, Jiangsu, China.
Department of Gynecology and Obstetrics, Wuxi Maternal and Child Health Hospital, the Affiliated Hospital of Nanjing Medical University, Wuxi, Jiangsu, China.
PLoS One. 2014 Jan 29;9(1):e87343. doi: 10.1371/journal.pone.0087343. eCollection 2014.
Intrahepatic cholestasis of pregnancy (ICP) is the most prevalent pregnancy specific liver disease. However, the pathogenesis and etiology of ICP is poorly understood.
To assess the expression of peroxisome proliferator-activated receptorγ (PPARγ) and nuclear factor kappa B (NF-κB) in placenta and HTR-8/SVneo cell, and evaluate the serum levels of cytokines, bile acids, hepatic function and lipids in control and ICP patients and the fetal outcome, in order to explore the role of PPARγ/NF-κB signaling pathway in the possible mechanism of ICP.
Clinical data of the pregnant women were collected and serum levels of cytokines, bile acids, hepatic function and lipids were measured. Expressions of PPARγ and NF-κB in placenta and HTR-8/SVneo cell were determined. The new-born information was collected to demonstrate the relationship between PPARγ/NF-κB signaling pathway and ICP.
The serum levels of bile acids, hepatic function, triglycerides (TG), total cholesterol (TC), IL-6, IL-12 and TNF-α in ICP group were significantly increased (P<0.01), and serum level of IL-4 was significantly decreased (P<0.01). PPARγ and NF-κB staining were found in the membrane and cytoplasm of placental trophoblast cell. The expression of PPARγ and NF-κB were significantly higher in ICP group and taurocholate acid (TCA) treated HTR-8/SVneo cell (P<0.01). The new-born information in severe ICP group were significantly different as compared to that in control group (P<0.05), and part of information in mild ICP group were also difference to that in control group (P<0.05).
The higher expressions of PPARγ and NF-κB in ICP placenta and TCA treated HTR-8/SVneo cell, together with the abnormal serum levels of cytokines, might induced by the imbalance of inflammatory and immune reaction, and then disturb placental bile acid and serum lipids transportation, finally result in fatal cholestasis which probably be one of the mechanism of ICP.
妊娠肝内胆汁淤积症（ICP）是最常见的妊娠特异性肝脏疾病。然而，ICP 的发病机制和病因尚不清楚。
评估过氧化物酶体增殖物激活受体γ（PPARγ）和核因子κB（NF-κB）在胎盘和 HTR-8/SVneo 细胞中的表达，评估对照组和 ICP 患者的血清细胞因子、胆汁酸、肝功能和血脂水平以及胎儿结局，以探讨 PPARγ/NF-κB 信号通路在 ICP 可能机制中的作用。
收集孕妇的临床资料，检测血清细胞因子、胆汁酸、肝功能和血脂水平，测定胎盘和 HTR-8/SVneo 细胞中 PPARγ 和 NF-κB 的表达，收集新生儿信息，以证明 PPARγ/NF-κB 信号通路与 ICP 的关系。
ICP 组血清胆汁酸、肝功能、甘油三酯（TG）、总胆固醇（TC）、白细胞介素-6（IL-6）、白细胞介素-12（IL-12）和肿瘤坏死因子-α（TNF-α）水平明显升高（P<0.01），白细胞介素-4（IL-4）水平明显降低（P<0.01）。胎盘滋养层细胞的膜和细胞质中均发现 PPARγ 和 NF-κB 染色。ICP 组和牛磺胆酸（TCA）处理的 HTR-8/SVneo 细胞中 PPARγ 和 NF-κB 的表达明显升高（P<0.01）。重度 ICP 组新生儿信息与对照组有明显差异（P<0.05），轻度 ICP 组部分信息与对照组也有差异（P<0.05）。
ICP 胎盘和 TCA 处理的 HTR-8/SVneo 细胞中 PPARγ 和 NF-κB 的高表达，以及细胞因子、胆汁酸和血清脂质代谢的失衡，可能是炎症和免疫反应失衡引起的，从而干扰胎盘胆汁酸和血清脂质的转运，最终导致致命性胆汁淤积，这可能是 ICP 的机制之一。
