妊娠期肝内胆汁淤积症患者胎盘组织白细胞介素10和肿瘤坏死因子α及细胞因子信号传导负调控因子3的表达

Expression profiles of IL-10, TNF-a, and SOCS3 in placenta of pregnant women with intrahepatic cholestasis

目的探讨细胞因子信号传导负调控因子3（SOCS3）、白细胞介素10（IL-10）及肿瘤坏死因子α（TNFα）在妊娠期肝内胆汁淤积症（ICP）孕妇胎盘组织中的表达及其意义。方法选择2010年10月至2011年5月在新疆医科大学第一附属医院产科剖宫产分娩的ICP孕妇37例为病例组，选择同期健康孕妇35例为对照组。采用Envision免疫组织化学法测定IL-10、TNFα在孕妇胎盘组织中的定位与表达水平，Western blot测定胎盘组织中SOCS3的表达水平。组间比较采用t检验，等级资料采用秩和检验，变量间的相关性采用Spearman相关分析。结果（1）IL-10、TNFα在两组孕妇胎盘组织中均有表达，在病例组中，IL-10的表达低于对照组（Z=-2．626，P〈0．01），而TNFα的表达则高于对照组（Z=-4．350，P〈0．01）。（2）SOCS3在两组孕妇胎盘组织中均有表达，病例组的表达水平低于对照组（t=-2．214，P〈0．05）。且其下降与IL-10呈正相关（r=0．494，P〈0．01），与TNFα呈负相关（r=-0．472，P〈0．01）。结论ICP患者母胎界面Th1型细胞因子TNFα表达增加，而Th2型细胞因子IL-10表达降低，存在Th1偏移。SOCS3可能通过影响细胞因子平衡而参与了ICP的发病。

Objeαive To deteα the expression profiles of suppressor ofcytokine signaling 3 （SOCS3）, interleukin （IL）-10, and tumor necrosis faαor-alpha （TNF-α in the placenta of women with intrahepatic cholestasis of pregnancy （ICP） and determine the clinical significance of the differential expressions. Methods Placentas were colleαed from 37 ICP gravidas who delivered through cesarean seαion at the First Teaching Hospital of Xingjiang Medical University from Oαober 2010 to May 2011 and from 35 healthy pregnant women （controls）. SOCS3, TNF-α, and IL-10 protein levels were deteαed by immunoblotting and the Envision method. Results TNF-α and IL-IO expression was deteαed in placentas of both groups, and was present mainly in the cytoplasm of trophoeytes. IL-10 expression was obviously lower in the ICP placentas than in the control placentas; meanwhile, TNF-α expression was obviously higher than in the control placentas （Z = -2.63, P 〈 0.01）. SOCS3 protein was significantly more abundant in the control placentas than in the ICP placentas. Furthermore, SOCS3 and IL-10 placental expressions were positively correlated （r = 0.494, P 〈 0.01）, but there was a negative correlation between SOCS3 and TNF-α placental expressions （r = -0.472, P 〈 0.01）. Conclusion In ICP, an increase of the type 1 cytokine, TNF-α, is associated with decreases of the type 2 cytokine, IL-10, and of SOCS3, which may reduce the secretion oflL-10. Furthermore, SOCS3 may contribute to ICP pathogenesis by modulating the Th1/Th2 cytokine balance.