MRP1，MRP2在胎盘上的表达与ICP的关系
摘要
【目的】探讨多药耐药相关蛋白MRP1、2在妊娠晚期胎盘中的表达以及其表达量与胆汁酸的关系,进一步研究胎盘胆盐载体在妊娠期肝内胆汁淤积症(ICP)的发病机制中的作用。
【方法】选取2008年3月至2009年10月间已确诊为ICP的孕妇30名(ICP组),正常晚孕妇女30名(对照组)。取其胎盘组织以及母体静脉血、脐静脉血,用免疫组化法测定胎盘中MRP1,MRP2的表达水平,同时测定母体血总胆汁酸水平和脐静脉血总胆汁酸水平。
【结果】(1)MRP1,MRP2在两组胎盘组织上均有表达;(2)ICP组胎盘组织MRP1的表达量高于对照组(2.57±1.43 VS 1.67±0.85,P<0.01);(3)ICP组胎盘组织MRP2的表达量低于对照组(1.47±0.82 VS 2.43±1.20,P<0.01),且表达量与脐血总胆汁酸水平呈负相关(R=-0.72,P<0.01);(4)ICP组中的母体血总胆汁酸及脐血总胆汁酸均高于对照组(34.61±23.25 VS 2.04±1.48,13.39±9.06 VS 3.45±1.86,P<0.01);(5)ICP组中母体血总胆汁酸与脐血总胆汁酸呈正相关(R=0.967,P<0.01)。
【结论】MRP1与MRP2蛋白均表达于孕晚期胎盘上。随着滋养细胞内胆汁酸浓度的增高,MRP2表达相应下降,MRP1表达增高,提示这两种蛋白均参与了胎盘上的胆汁酸转运,其转运能力的变化可能是导致胎儿胆汁淤积的原因之一。MRP2的表达与脐血胆汁酸呈负相关,说明它的转运能力在胆盐转运中发挥重要作用。ICP时,母血和脐血胆汁酸都增高,且两者有密切关系。通过对母血胆汁酸的检测有助于了解胎儿胆汁淤积的程度。
Objective: To study the placental expression of MRP1,MRP2 in third trimester of pregnancy and their relationship with total bile acid, which helps doing further study on the effects of the three proteins on intrahepatic cholestasis of pregnancy.
Methods: Pick up 30 ICP cases, who have been diagnosed during Mar.2008 and Oct.2009, as the ICP group and 30 normal pregnant women at the same period as the control group. The expression of placental MRP1,MRP2 are detected in immunehistochemistry, the maternal and umbilical total bile acid levels are detected as well.
Results: (1) Both MRP1 and MRP2 express in placenta in both groups. (2) The expression level of MRP1 in placenta in ICP group is higher than control group(2.57±1.43 VS 1.67±0.85,P<0.01). (3) The expression level of MRP2 in placenta in ICP group is lower than control group(1.47±0.82 VS 2.43±1.20,P<0.01). Moreover, there is a negative correlation of the MRP2 expression level and the umbilical total bile acid level in ICP group(R=-0.72,P<0.01)(.4) Both maternal and umbilical total bile acid levels in ICP group are higher than control group(34.61±23.25 VS 2.04±1.48,13.39±9.06 VS 3.45±1.86,P<0.01). (5) There is a positive correlation of maternal and umbilical total bile acid in ICP group(R=0.967,P<0.01).
Conclusion: Both MRP1 and MRP2 express in placenta in third trimester of pregnancy. With the increasing level of TBA, the expression of MRP1 rises while MRP2 falls, which mean the two proteins participate in the transporting of bile acids. The varieties of their capacities of transporting may causes the cholestasis in fetus. there is a negative correlation of the MRP2 expression level and the umbilical total bile acid level in ICP group. It illustrates that MRP2 may be plays an important role in bile acids transporting in placenta. The maternal and umbilical total bile acid levels are higher in ICP, and there is a positive correlation of them. Detecting the maternal TBA level can help understanding the cholestasis of fetus.
【方法】选取2008年3月至2009年10月间已确诊为ICP的孕妇30名(ICP组),正常晚孕妇女30名(对照组)。取其胎盘组织以及母体静脉血、脐静脉血,用免疫组化法测定胎盘中MRP1,MRP2的表达水平,同时测定母体血总胆汁酸水平和脐静脉血总胆汁酸水平。
【结果】(1)MRP1,MRP2在两组胎盘组织上均有表达;(2)ICP组胎盘组织MRP1的表达量高于对照组(2.57±1.43 VS 1.67±0.85,P<0.01);(3)ICP组胎盘组织MRP2的表达量低于对照组(1.47±0.82 VS 2.43±1.20,P<0.01),且表达量与脐血总胆汁酸水平呈负相关(R=-0.72,P<0.01);(4)ICP组中的母体血总胆汁酸及脐血总胆汁酸均高于对照组(34.61±23.25 VS 2.04±1.48,13.39±9.06 VS 3.45±1.86,P<0.01);(5)ICP组中母体血总胆汁酸与脐血总胆汁酸呈正相关(R=0.967,P<0.01)。
【结论】MRP1与MRP2蛋白均表达于孕晚期胎盘上。随着滋养细胞内胆汁酸浓度的增高,MRP2表达相应下降,MRP1表达增高,提示这两种蛋白均参与了胎盘上的胆汁酸转运,其转运能力的变化可能是导致胎儿胆汁淤积的原因之一。MRP2的表达与脐血胆汁酸呈负相关,说明它的转运能力在胆盐转运中发挥重要作用。ICP时,母血和脐血胆汁酸都增高,且两者有密切关系。通过对母血胆汁酸的检测有助于了解胎儿胆汁淤积的程度。
Objective: To study the placental expression of MRP1,MRP2 in third trimester of pregnancy and their relationship with total bile acid, which helps doing further study on the effects of the three proteins on intrahepatic cholestasis of pregnancy.
Methods: Pick up 30 ICP cases, who have been diagnosed during Mar.2008 and Oct.2009, as the ICP group and 30 normal pregnant women at the same period as the control group. The expression of placental MRP1,MRP2 are detected in immunehistochemistry, the maternal and umbilical total bile acid levels are detected as well.
Results: (1) Both MRP1 and MRP2 express in placenta in both groups. (2) The expression level of MRP1 in placenta in ICP group is higher than control group(2.57±1.43 VS 1.67±0.85,P<0.01). (3) The expression level of MRP2 in placenta in ICP group is lower than control group(1.47±0.82 VS 2.43±1.20,P<0.01). Moreover, there is a negative correlation of the MRP2 expression level and the umbilical total bile acid level in ICP group(R=-0.72,P<0.01)(.4) Both maternal and umbilical total bile acid levels in ICP group are higher than control group(34.61±23.25 VS 2.04±1.48,13.39±9.06 VS 3.45±1.86,P<0.01). (5) There is a positive correlation of maternal and umbilical total bile acid in ICP group(R=0.967,P<0.01).
Conclusion: Both MRP1 and MRP2 express in placenta in third trimester of pregnancy. With the increasing level of TBA, the expression of MRP1 rises while MRP2 falls, which mean the two proteins participate in the transporting of bile acids. The varieties of their capacities of transporting may causes the cholestasis in fetus. there is a negative correlation of the MRP2 expression level and the umbilical total bile acid level in ICP group. It illustrates that MRP2 may be plays an important role in bile acids transporting in placenta. The maternal and umbilical total bile acid levels are higher in ICP, and there is a positive correlation of them. Detecting the maternal TBA level can help understanding the cholestasis of fetus.
引文
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