PPARγ/NF-κB信号通路在妊娠期肝内胆汁淤积症发病中的作用及机制研究

妊娠期肝内胆汁淤积症（ICP）是妊娠期危害母婴健康的并发症，母胎免疫平衡失调在ICP发病中起着关键作用。研究表明，PPARγ对NF-κB及其下游细胞因子在免疫炎症反应中具有调控作用，但PPARγ通过调控NF-κB及其下游细胞因子在ICP发病中的作用尚不清除。我们的前期研究发现，ICP患者胎盘PPARγ和NF-κB过表达，血清IL-6、IL-12和TNF-α水平升高，IL-4水平降低，体外实验进一步验证此结果。我们的预实验发现经胆酸处理的HTR8/SVneo细胞干扰或过表达PPARγ可以调控NF-κB的表达。据此，我们提出PPARγ-NF-κB-细胞因子通路参与ICP发病机制的假说。本研究拟通过在体及离体实验观察PPARγ-NF-κB-细胞因子通路在ICP发病中的作用，阐明PPARγ/NF-κB信号通路在ICP形成中的分子机制，可为ICP的治疗提供新的靶点和理论依据。

Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy-specific complication that may impair the health of maternity and infant, the immune imbalance of maternal-fetal play the key roles in the pathogenesis of ICP. Recent studies have shown that peroxisome proliferator-activated receptor γ (PPAR γ) could regulation of nuclear factor kappa B (NF-κB) and its downstream cytokines in the immune and inflammatory response, but the role of PPAR γ regulation of NF-κB in the pathogenesis of ICP is not clear. Our previous studies showed that PPAR γ and NF-κB over expression in the placenta tissue of ICP patients, serum IL-6, IL-12 and TNF-α levels were increased, IL-4 levels was decreased, and the results were further validated in vitro. Our preliminary findings showed that siRNA PPAR γ or over expression of PPAR γ in taurocholate acid treatment HTR8/SVneo cell could regulate the expression of NF-κB. On the basis of preliminary experiment research, we propose the hypothesis that PPAR γ-NF-κB-cytokine pathway is involved in the pathogenesis of ICP. In this study, we will through in vivo and in vitro experiments investigate the roles of PPAR γ-NF-κB-cytokine pathway in the pathogenesis of ICP, and clarify the molecule mechanism of PPAR γ/NF-κB signaling pathway in the formation of ICP, which may provide new target and theoretical basis for the treatment of ICP.