Study On The Relationship Between The Placental Expression Of MPR1,MRP2 And Intrahepatic Cholestasis Of Pregnancy

[Object]To explore the placental expression of MRP1 and MRP2, as well as maternal and umbilical cord serum total bile acid (TBA) levels and the variation of bile acid compositions. To evaluate the relation between the placental bile salt transporters and intrahepatic cholestasis of pregnancy.[Materials and Methods]Maternal and umbilical cord serum total bile acid (TBA) and bile acid compositions levels were measured in 20 pregnant women with ICP(ICP group) and 20 normal pregnant women(control group) by Velocimetry and HPLC-MS/MS respectively. The placental MRP1 and MRP2 mRNA expression of 8 first trimester placenta, 7 second trimester placentas and two above groups' placentas were examined by real time RT-PCR.[Results]1. The TBA levels of maternal serum and umbilical cord in ICP group were compared individually with those in the control group, the former were significantly higher than the latter (P＜0.05). Maternal serum TBA levels were significantly higher than those in the umbilical cord blood in ICP group(46.15±62.82 VS 18.23±16.77)μmol/L (P＜0.05). Maternal serum TBA levels were significantly lower than those in the umbilical cord blood in control group (2.82±1.82 VS 4.79±1.26)μmol/L (P＜0.05).2. The maternal serum CA, TCA, TDCA, TCDCA, GCA and GCDCA levels in ICP group were compared with those in the control group, the former were significantly higher than the latter(P＜0.05), while DCA levels were significantly lower than the latter(P＜0.05). The CA, TCA, TDCA, GCA, GCDCA and LCA levels of umbilical cord in ICP group were significantly higher than those in the control group(P＜0.05).3. The DCA, TCA, TDCA, TCDCA, GCA levels in maternal serum were significantly higher than those in the umbilical cord blood in ICP group(P＜0.05). The DCA, TDCA, LCA levels in maternal serum were significantly higher than those in the umbilical cord blood in control group, while the TCDCA levels were significantly lower than those in the umbilical cord blood (P＜0.05).4. The MRP2 mRNA was expressed in the placentas of ICP group and in every trimester of normal pregnancy, while the MRP1 mRNA was expressed in most of placentas. The MRP1 and MRP2 mRNA expression levels were no difference between two groups (99.94±73.17 VS 99.20±68.65; 95.78±56.50 VS 142.20±91.27) (P＞0.05). The MRP2 mRNA expression levels in ICP group which were not treated by dexarnethasone were lower than that in the control group (91.82±48.08 VS 142.20±91.27) (P＜0.05). The MRP2 mRNA expression levels in third trimester were significantly higher than those in the second trimester (P＜0.05).5. There were no significant correlation between TBA or bile acid compositions levels and MRP1 and MRP2 mRNA express levels in ICP group (P＞0.05). There was a negative correlation between the MRP2 mRNA expression levels in control group and the TDCA levels of umbilical cord (r=-0.582, P＜0.05).[Conclusion]The TBA levels of umbilical cord and maternal serum increased in patients with ICE The main feature of ICP maternal serum is that CA/CDCA＞1, the bile acid combined with aminoacetic acid/the bile acid combined with aminoethylsulfonic acid＜1. The results suggested that the expression of MRP2 mRNA on placentas falls in patients with ICP which were not treated by dexamethasone. The dysfunction of placenta bile acid transport may be one of the mechanisms of fetal cholestasis in ICP...