胎盘CYP3A4的表达及其与ICP关系的研究

目的探讨细胞色素P4503A4（CYP3A4）酶在正常晚孕和妊娠期肝内胆汁淤积症（intrahepatic cholestasis of pregnancy，ICP）胎盘的表达及其与母血和脐血总胆汁酸（total bile acids，TBA）水平的关系，进一步分析胎盘CYP3A4在ICP病理机制中的作用。方法采用实时荧光定量巢式PCR（RT—Nested PCR）法测定胎盘组织中CYP3A4 mRNA的表达量；采用速率法测定母血、脐血中总胆汁酸的水平。结果（1）对照组及ICP组胎盘组织中均有CYP3A4 mRNA的表达，ICP组胎盘组织中CYP3A4 mRNA表达量低干对照组（0．50（1．41）vs1．41（1．57）），差异有统计学意义（P〈0．05）；ICP地塞米松dexamethasone，DEX）治疗组CYP3A4 mRNA表达量高于未用DEX治疗组（0．59（1．27）VS0．21（1.09）），差异有统计学意义（P〈0．05）。（2）对照组及ICP组胎盘组织中CYP3A4 mRNA表达量与母、脐血中TBA水平之间均不具有相关性（n=-0．060～-0．330，P均〉0．05）。结论（1）ICP胎盘CYP3A4 mRNA的表达降低，使胎盘对胆汁酸的解毒作用减弱，这可能与ICP胎儿病理机制有关。（2）DEX是ICP胎盘CYP3A4的诱导剂，这可能是其治疗ICP的机制之一。

Study on the relationship between the placental expression of CYP3A4 and intrahepatic cholestasis of pregnancy

Objectives To investigate the CYP3A4 expression in the placentas of normal late pregnancy and intrahepatic eholestasis of pregnancy（ICP） ,as well as their relationship with total bile aeids（TBA）levels in maternal and umbilical cord serum. To evaluate the roles of placental CYP3A4 in the pathological mechanism of ICP. Methods Real time nested PCR was applied for the measurement of placental CYP3A4 mRNA expression. TBA levels were measured by veloeimetry. Results （1） CYP3A4 mRNA was deteeted in placen.tas of control group as well as ICP group. Placental CYP3A4 mRNA expression was significantly lower in ICP group than that in control group （0.50 （ 1.41 ）VS 1.41 （ 1.57 ）, P〈0.05 ）. The CYP3A4 mRNA expression was significantly higher in ICP group treated by dexamethasone （DEX） than that in non-DEX treated group （0.59 （ 1.27 ）VS 0.21 （ 1.09 ）, P〈0.05 ）. （2） There were no correlations between the placental CYP3A4 mRNA expression and the maternal or umbilical cord serum TBA levels both in control group and ICP group （rs = - 0.060 - - 0.330, respectively, P〉0.05 ）. Conclusion （1） CYP3A4 mRNA expression is down regnlated in ICP placenta, decreased detoxieity on bile acid by placenta is probably involved in the pathological mechanism of poor perinatal prognosis in ICP. （2） DEX is the inducer of CYP3A4 in ICP plaeenta, which may represent the benifical effect of DEX for ICP.