CYP7B1与ER在胆汁淤积孕鼠胎鼠肝脏中的表达

Expression of CYP7B1 and ER mRNA in fetus liver of intrahepatic cholestasis of pregnant rats

目的探讨雌激素受体（ERα、ERβ）与胆固醇7d羟化酶（CYP781）mRNA在妊娠期肝内胆汁淤积（ICP）孕鼠、胎鼠肝脏中的表达及其意义。方法对照组孕鼠30只注射精制植物油；研究组孕鼠30只注射17－α－乙炔雌二醇。两组孕鼠分别于妊娠第13天、17天、21天断尾采母鼠血检测，于妊娠第21天抽取母鼠、胎鼠血并提取肝脏组织。应用酶联免疫吸附试验检测两组孕鼠及胎鼠血清中胆酸水平；应用实时定量PCR技术检测两组胎鼠肝脏ERa、ERl3、CYP781mRNA的表达。结果①在妊娠第17天、21天研究组母鼠胆汁酸水平明显高于对照组（55．7±3．2μmol／Lvs23．4±1．2μmol／L。t=2．541，P〈0．05；61．4±2．4μmol／Lvs25．5±2．1μmol／L，t=2．621，P〈0．05）；研究组胎鼠胆汁酸水平明显高于对照组（27．4±2．3μmol／Lvs11．54-2．6μmol／L，t=2．631，P〈0．05）；②研究组胎鼠肝脏CYP781mRNA水平明显高于对照组（2．15±0．01vs0．25±0．02，t=2．563，P〈0．05）；⑧研究组ER仅mRNA水平明显高于对照组（0．81±0．02vs0．35±0．01，t=2．534，P〈0．01）。结论ICP孕鼠胎鼠肝细胞ER旺、CYP781的表达升高，胆汁酸的合成与代谢调节机制存在障碍，可能是导致ICP胎儿围生儿死亡发生的原因之一。

Objective To study the expression and significance of estrogen receptor （ERa, ERI3 ） and cholesterol 12a-hydroxylase （CYP7B1） mRNA in fetus liver of intrahepatic cholestasis of pregnant rats. Methods Thirty clean SD pregnant rats in control group were injected subcutaneously with refined vegetable oil, and another 30 clean SD pregnant rats in research group were injected subcutaneously with 17-a-ethynylestradio（EE） . Blood of pregnant rats in two groups were tested on the 13th, 17th and 21st day, and blood of mother rats and fetus rats were taken at 21st day and their livers were collected for study. The levels of serum TBA were examined by ELISA, and the expressions of ERα, ERβ, CYP7B1 mRNA in fetus livers of two groups were examined by real-time PCR. Results The level of TBA was significantly higher in mother rats in research group than that in control group on the 17th and 21st day （55.7 ± 3.21xmol/L vs 23.4± 1.2μmol/L, t = 2.541, P 〈 0.05 ;61.4 ± 2.4 p, mol/L vs 25.5± 2.1 μmol/L, t = 2. 621, P 〈 0.05 ）, so was the level of TBA in fetus rats on the 21 st day （27.4 ± 2.3 μmol/L vs 11.5± 2.6 μmol/L, t = 2.631, P 〈 0.05 ）. The expression of CYP7 B1 mRNA in fetus liver in research group was significantly higher than that in control group （ 2.15±0.01vs 0. 25 ±0.02, t = 2. 563, P 〈 0.05 ）. The expression of ERa mRNA in research group was remarkably higher than that in control group （0. 81 ±.02 vs 0.35 ±0.01, t =2. 534,P 〈0.01）. Conclusion The expressions of ERa and CYP7B1 in liver of pregnant rats with intrahepatic cholestasis and fetus rats elevate, and the mechanism of TBA synthesis and metabolism is in disorder, which may be one of the causes of ICP perinatal fetus mortality.