胎盘中FXR、BSEP的表达及其与ICP关系的研究
摘要
目的:探讨ICP胎盘中FXR、BSEP的表达,以及母、脐血清中CG(甘胆酸)水平的变化,进而从胎盘角度探讨ICP发病机制。
方法:以35例ICP患者为ICP组,对照组为40例正常妊娠者。采用放射免疫法测定两组母、脐血清CG水平,生化测定母血清肝功能指标(ALT、ALP、T-BIL、TBA等);免疫组织化学SP法测定两组胎盘组织中FXR、BSEP的表达。
结果:(1)母血清CG值ICP组较对照组明显升高(18507.14±6614.01ng/ml VS 1411.75±406.89ng/ml)、脐血清CG值ICP组较对照组也升高(6899.14±1823.05 ng/ml VS 2341.50±633.62ng/ml),两者均有极显著差异,P<0.01。ICP组CG水平母血清明显高于脐血清,两者间成正相关,相关系数r=0.84,P<0.01。(2)母血清ALT、AST、ALP、TBA、T-BIL等值ICP组均较对照组升高,其中ICP组ALP值与母、脐血清CG水平呈正相关,相关系数分别为0.68、0.61,P<0.01。(3)ICP组与对照组胎盘中均有FXR、BSEP的表达,ICP组FXR的表达较对照组增加(16.54±2.16% VS 11.38±1.44 %),BSEP的表达则低于对照组(4.94±1.11% VS 7.53±1.04%),两者均有统计学意义,P<0.01。(4)ICP组胎盘组织中FXR(16.54±2.16%)的表达与母血清(18507.14±6614.01 ng/ml)、脐血清(6899.14±1823.05 ng/ml)CG水平呈正相关性,相关系数分别为0.58、0.54, P<0.01。BSEP(4.94±1.11)%的表达量与母血清、脐血清CG水平呈负相关性,相关系数分别为-0.42、-0.30, P<0.05。
结论:ICP组母、脐血清CG水平明显高于对照组。ICP时,患者胎盘上FXR表达虽明显增强,但BSEP的表达并未因此而上调,反而表达减低,引起胎盘排泌胎儿胆汁酸下降,胎儿体内胆汁酸淤积,可能是ICP发病机制之一。
Objective:To explore the expression of placental FXR、BSEP,as well as maternal and umbilical cord serum glycocholic acicd(CG) levels.To evaluate the pathogenesis of intrahepatic cholestasis of pregnancy(ICP).
Methods:CG levels in 35 cases of ICP and 40 cases of normal pregnancy as compared group were detected in maternal and umbilical cord serum by radioimmunoassay and hepatic function,such as alkaline phosphatase(ALP)、aspartate aminotransferase(AST)、total bile acid(TBA),was also detected.The express of FXR and BSEP in placenta were detected in both guoups by SP of immunohistochemistry.
Results:(1)Maternal and umbilical cord serum CG levels in ICP group were all significantly higher than the control group ( 18507.14±6614.01ng/ml VS 1411.75±406.89ng/ml)、(6899.14±1823.05ng/ml VS 2341.50±633.62ng/ml)(P<0.01). The CG level of maternal serum was higher than those of umbilical cord serum, and there was a positive correlation in CG level between in maternal and umbilical cord serum in ICP group(r=0.84). (2)The ALT、AST、ALP、TBA et al level of maternal serum in ICP group were all higher than those of maternal serum in control group. There was a positive correlation in ALP level and maternal serum CG level in ICP group(r=0.68). (3)The expression of FXR and BSEP were all founded in both groups,and the expression of FXR was more in ICP group than control group(16.54±2.16% VS 11.38±1.44 %)(P<0.01),on the contrary ,the BSEP level was lower in ICP group than control group ( 4.94±1.11% VS 7.53±1.04% ) (P<0.01).(4)There was a positive correlation in expression of FXR and CG level of maternal and umbilical cord serum in ICP group(r=0.58、0.54).However,between the expression of BSEP and the CG level of maternal and umbilical cord serum,there was a negative correlation in ICP group(r=-0.42、-0.30).
Conclusion: The CG level in maternal and umbilical cord serum in ICP group was significantly higher than that of control group. The expression of FXR was more in ICP group than control group. Then, the expression of BSEP on placenta falls in patients with ICP. The dysfunction of placenta transport bile acid resulted in fetal cholestasis,this may be one of the mechanisms of ICP.
方法:以35例ICP患者为ICP组,对照组为40例正常妊娠者。采用放射免疫法测定两组母、脐血清CG水平,生化测定母血清肝功能指标(ALT、ALP、T-BIL、TBA等);免疫组织化学SP法测定两组胎盘组织中FXR、BSEP的表达。
结果:(1)母血清CG值ICP组较对照组明显升高(18507.14±6614.01ng/ml VS 1411.75±406.89ng/ml)、脐血清CG值ICP组较对照组也升高(6899.14±1823.05 ng/ml VS 2341.50±633.62ng/ml),两者均有极显著差异,P<0.01。ICP组CG水平母血清明显高于脐血清,两者间成正相关,相关系数r=0.84,P<0.01。(2)母血清ALT、AST、ALP、TBA、T-BIL等值ICP组均较对照组升高,其中ICP组ALP值与母、脐血清CG水平呈正相关,相关系数分别为0.68、0.61,P<0.01。(3)ICP组与对照组胎盘中均有FXR、BSEP的表达,ICP组FXR的表达较对照组增加(16.54±2.16% VS 11.38±1.44 %),BSEP的表达则低于对照组(4.94±1.11% VS 7.53±1.04%),两者均有统计学意义,P<0.01。(4)ICP组胎盘组织中FXR(16.54±2.16%)的表达与母血清(18507.14±6614.01 ng/ml)、脐血清(6899.14±1823.05 ng/ml)CG水平呈正相关性,相关系数分别为0.58、0.54, P<0.01。BSEP(4.94±1.11)%的表达量与母血清、脐血清CG水平呈负相关性,相关系数分别为-0.42、-0.30, P<0.05。
结论:ICP组母、脐血清CG水平明显高于对照组。ICP时,患者胎盘上FXR表达虽明显增强,但BSEP的表达并未因此而上调,反而表达减低,引起胎盘排泌胎儿胆汁酸下降,胎儿体内胆汁酸淤积,可能是ICP发病机制之一。
Objective:To explore the expression of placental FXR、BSEP,as well as maternal and umbilical cord serum glycocholic acicd(CG) levels.To evaluate the pathogenesis of intrahepatic cholestasis of pregnancy(ICP).
Methods:CG levels in 35 cases of ICP and 40 cases of normal pregnancy as compared group were detected in maternal and umbilical cord serum by radioimmunoassay and hepatic function,such as alkaline phosphatase(ALP)、aspartate aminotransferase(AST)、total bile acid(TBA),was also detected.The express of FXR and BSEP in placenta were detected in both guoups by SP of immunohistochemistry.
Results:(1)Maternal and umbilical cord serum CG levels in ICP group were all significantly higher than the control group ( 18507.14±6614.01ng/ml VS 1411.75±406.89ng/ml)、(6899.14±1823.05ng/ml VS 2341.50±633.62ng/ml)(P<0.01). The CG level of maternal serum was higher than those of umbilical cord serum, and there was a positive correlation in CG level between in maternal and umbilical cord serum in ICP group(r=0.84). (2)The ALT、AST、ALP、TBA et al level of maternal serum in ICP group were all higher than those of maternal serum in control group. There was a positive correlation in ALP level and maternal serum CG level in ICP group(r=0.68). (3)The expression of FXR and BSEP were all founded in both groups,and the expression of FXR was more in ICP group than control group(16.54±2.16% VS 11.38±1.44 %)(P<0.01),on the contrary ,the BSEP level was lower in ICP group than control group ( 4.94±1.11% VS 7.53±1.04% ) (P<0.01).(4)There was a positive correlation in expression of FXR and CG level of maternal and umbilical cord serum in ICP group(r=0.58、0.54).However,between the expression of BSEP and the CG level of maternal and umbilical cord serum,there was a negative correlation in ICP group(r=-0.42、-0.30).
Conclusion: The CG level in maternal and umbilical cord serum in ICP group was significantly higher than that of control group. The expression of FXR was more in ICP group than control group. Then, the expression of BSEP on placenta falls in patients with ICP. The dysfunction of placenta transport bile acid resulted in fetal cholestasis,this may be one of the mechanisms of ICP.
引文
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