雌激素受体α对胆汁酸转运相关基因的调控及其与孕鼠肝内胆汁淤积症发生的相关性  

Regulation of estrogen receptor α on bile acid transporters related gene and its correlation with intrahepatic cholestasis in pregnant rats

作　　者：宋昭逸 王晶晶[2] 时青云[1,3] 

机构地区：[1]北京大学第九临床医学院妇产科,北京100038 [2]首都医科大学动物实验中心,北京100069 [3]首都医科大学附属北京世纪坛医院妇产科,北京100038

出　　处：《中国计划生育和妇产科》2016年第10期56-58,62,共4页Chinese Journal of Family Planning & Gynecotokology

基　　金：国家自然科学基金(编号:81170588)

摘　　要：目的探讨雌激素受体α(estrogen receptorα,ERα)对参与调节胆汁酸转运相关的基因,如法尼醇X受体(farnesoid X receptor,FXR)、钠离子-牛磺胆酸共转运蛋白(sodium taurocholate co-transprorting polypeptide,NTCP)、胆盐输出泵(bile salt export pump,BSEP)的调控作用及其对孕鼠肝内胆汁淤积发生的影响。方法将40只SPF级SD孕鼠随机均分为4组。自孕第15 d起,对照组颈部皮下注射精制植物油2.0 m L/kg·d;低、中、高剂量组分别皮下注射17α-乙炔雌二醇1.0 mg/kg·d、1.25 mg/kg·d、1.5 mg/kg·d。于妊娠第21 d采血2 m L,后采用颈部脱臼法处死,提取母鼠肝脏行活体组织学检查。检测各组孕鼠血清中的生化指标及肝脏组织中各目的蛋白和mRNA表达量。结果生化指标:低、中、高剂量组孕鼠各蛋白表达水平明显高于对照组,差异有统计学意义(P<0.05),低、中、高剂量组组间比较,差异有统计学意义(P<0.05);蛋白表达及mRNA的表达水平:ER在对照组、低剂量组、中剂量组、高剂量组的表达量依次升高,而FXR、NTCP、BSEP在对照组、低剂量组、中剂量组、高剂量组的表达量依次降低,各组目的基因表达量与对照组比较,差异均有统计学意义(P<0.05)。结论随着雌激素剂量的增加,ERα表达水平升高,而FXR、NTCP、BSEP表达水平均降低,提示胆汁酸代谢转运功能降低,可能为雌激素诱导孕鼠肝内胆汁淤积的发生机制之一。Objective To investigate the regulation of estrogen receptor α（ERα）on bile acid transporters related gene, such as farnesoid X receptor （FXR） , sodium taurocholate co-transporting polypeptide （NTCP）and bile salt export pump （BSEP） ,to evaluate ERα＇ s correlation with intrahepatic cholestasis in pregnant rats. Methods Forty SPF class pregnant Sprague-Dawley rats were selected and divided into four groups randomly with 10 in each. Since the 15th day of pregnancy, rats in control group were injected subcutaneously with refined vegetable oil 2.0 mL/kg . d, those in the low-dose, moderate-dose and high-dose groups received 17α- ethynylestradiol （EE） 1.0 mg/kg . d, 1.25 mg/kg . d, 1.5 mg/kg . d. All rats were sacrificed on the 21st day of pregnancy andmaternal hepatic tissue were collected. The serum levels of biochemical indicators, protein and mRNA expressions of ERa FXR, NTCP, BSEP were examined. Results Biochemical： the serum levels of ALT, AST, TBS, BIL were significantly lower in the control group than that in the treatment groups （P 〈 0. 05 ）. Protein and mRNA expression of ERa, FXR, NTCP, BSEP： compared witb control group, low-dose, moderate-dose, high-dose group activated ERa significantly; FXR, NTCP, BSEP decreased in a dose- dependent manner, which were all significantly lower than that in control group （ P 〈 0. 05 ）. Conclusions Along with the rise of estrogen,the repression of ERa rise and FXR, NTCP, BSEP decrease, these findings suggest lower metabolism and transporting function of bile acid. We propose that this may contribute to development of the EE-indueed intrahepatie cholestasis of pregnancy.

关 键 词：妊娠期肝内胆汁淤积 雌激素受体 胆汁酸转运相关基因 法尼醇X受体 钠离子-牛磺胆酸共转运蛋白 胆盐 输出泵 

分 类 号：R332[医药卫生—人体生理学]