胎盘FIC1 mRNA的表达及其与ICP关系的研究

Study on Relationship Between Expression of Familial Intrahepatic Cholestasis 1 mRNA in Placenta and Intrahepatic Cholestasis of Pregnancy

目的通过研究妊娠期肝内胆汁淤积症（ICP）胎盘胆盐载体家族性肝内胆汁淤积相关蛋白-1（FIC1）mRNA的表达,以及母胎血中总胆汁酸（TBA）和甘胆酸（CG）水平的变化,探讨胎盘胆盐载体在ICP胎儿病理机制中的作用。方法纳入ICP患者（ICP组）及正常孕妇（对照组）各20例。采用速率法测定母体静脉、脐静脉血中TBA水平;测定放射免疫法CG水平;RT-PCR法测定胎盘组织中胆盐载体FIC1 mRNA表达;另采用原位杂交法对随机选取的两组各两例胎盘组织进行FIC1 mRNA的定位检测。结果1ICP组母血和脐血中的TBA、CG水平均高于对照组,差异有统计学意义（P〈0.05）。ICP组母血中TBA、CG水平均高于脐血（25.77±16.64）μmol/Lvs（8.55±5.48）μmol/L;（3416.09±1986.04）μg/dLvs（821.84±673.17）μg/dL,差异有统计学意义（P〈0.05）;对照组母血和脐血中TBA水平（3.40±2.51）μmol/Lvs（4.37±3.26）μmol/L、CG水平（342.74±234.88）μg/dLvs（309.32±145.20）μg/dL比较,差异无统计学意义（P〉0.05）。2ICP组、对照组胎盘组织中均有FIC1 mRNA的表达,且均定位于合体滋养细胞。ICP组FIC1 mRNA表达量低于对照组（0.76±1.22vs37.28±75.03）,差异有统计学意义（P〈0.05）。3ICP组和对照组胎盘组织中FIC1 mRNA表达量与母血、脐血中TBA和CG水平均无相关性（r=-0.229-0.163,P〉0.05）。结论胎盘FIC1 mRNA表达降低,这可能是导致胎盘对胆汁酸的转运障碍,引起ICP胎儿体内胆淤的因素之一。

Objective By detecting the expression of placental familial intrahepatic cholestasis 1 （FIC1） and levels of total bile acids （TBA） and cholylglycine （CG） in maternal and umbilical cord serum, the effect of placental bile salt transporter on fetal pathology of intrahepatic cholestasis of pregnancy （ICP） is explored. Methods TBA and CG levels in maternal and umbilical cord serum of 20 gravidas complicated with ICP （ICP group ） and 20 normal gravidas （control group ） of late pregnancy were measured by veloclmetry and radioimmunoassay respectively. The placental FIC1 mRNA expression was tested by real time RT-PCR. Meanwhile FIC1 mRNA expression of 4 random placentas were localized by in-situ hybridization. Results （1）TBA and CG levels in both maternal and umbilical cord serum of ICP group were significantly higher than those of control group （P〈0.05）. TBA and CG levels in maternal serum were significantly higher than those in umbilical cord serum of ICP group（25. 77±16.64）μmol/L vs （8.55±5.48） μmol/L for TEA, and （3416.09±1986.04）μg/dL vs （821.84±673. 17） μg/dL for CG, P〈0.05）. However, there were no significant differences between TBA and CG levels in maternal serum and umbilical cord serum from control group（3.4±2.51） μmol/L vs （4.36 ±3.26） μmol/L for TBA, and （342.74±234.88） μg/dL vs （309.32±145.20） μg/dL for CG ,P〉0.05）. （2）FIC1 mRNA was expressed and localized to syncytiotrophoblast in both ICP and control placentas. Placental FIC1 mRNA expression was significantly decreased in ICP group than in control group（P〈0.05）. （3） There were no significant correlations between TBA and CG levels of maternal or umbilical cord serum and expression of placental FIC1 mRNA in both groups （r=-0. 229-0. 163, P〉0.05）. Conclusion Our research results suggest that the decreased expression of FIC1 mRNA in placenta may be one of actor of disturbing placental bile salt transport and resulting in fetal cholestasis in ICP.