古拉定对雌激素诱导的肝内胆汁淤积症孕鼠的胎盘多药耐药相关蛋白-谷胱甘肽共转运体系的影响  

Effects of glutathione on MRP- GSH transportation system in rats with ethinyl estradiol induced intrahepatic cholestasis of pregnancy

作　　者：许张晔[1] 赵峰[2] 项慧秋 梁勇[3] 王斯璐[3] 黄引平[1] 

机构地区：[1]温州医科大学附属第一医院妇产科,浙江温州325000 [2]温州医科大学附属第一医院创伤外科,浙江温州325000 [3]温州医科大学附属第一医院外科实验室,浙江温州325000

出　　处：《中国卫生检验杂志》2014年第3期344-348,共5页Chinese Journal of Health Laboratory Technology

基　　金：温州市科技局项目(Y20100013)

摘　　要：目的探讨古拉定对雌激素诱导的肝内胆汁淤积症孕鼠的胎盘多药耐药相关蛋白-谷胱甘肽共转运体系的影响。方法用将妊娠第13 d的大鼠随机分成对照组,EE组,EE+古拉定组,17-α-乙炔雌二醇诱导建立孕鼠ICP模型,测定三组血清TBA、CG、ALT、AST;ELISA检测GSH,逆转录实时荧光定量PCR和免疫组化法检测MRP1、MRP2、MRP5的表达。结果 EE组TBA、CG、ALT、AST水平显著增高,胚胎存活率显著降低(P<0.001),经古拉定治疗,TBA、CG、ALT、AST水平显著下降,增加了胚胎存活率(P<0.01);EE组胎盘MRP1 mRNA和蛋白的表达显著上调(P<0.05),而胎盘MRP2、MRP5 mRNA和蛋白的表达显著下调(P<0.01),GSH显著下降(P<0.001);经过古拉定治疗,下调胎盘MRP1,上调MRP2和MRP5mRNA和蛋白的表达(P<0.05),GSH显著上升。结论胎盘存在MRP-GSH共转运体系;古拉定可以通过调节胎盘MRP-GSH共转运体系影响胆汁酸的转运来治疗大鼠妊娠期肝内胆汁淤积症。Objective To study the effects of glutathione on MRP - GSH transportation system in rats with ethinylestradiol - in- duced intrahepatic cholestasis of pregnancy. Methods The 13 -day- gestation pregnant rats were divided into control group, EE group, EE ＋ glutathione group to determine the serum TBA, CG, ALT and AST, and GSH was detected by ELISA, the ex- pression of MRP1, MRP2 and MRP5 were detected by real - time RT - PCR and immunohistochemical method. An ICP rat model was established with 17 - （x - ethinyl estradiol induction. Results TBA, CG, ALT and AST levels in EE group signifi- cantly increased, while embryo survival rate significantly decreased（ P 〈 0.001 ）. After glutathione treatment, TBA, CG, ALT and AST levels dropped significantly, and the embryo survival rate increased（ P 〈 0.01 ）. Placenta MRPI mRNA and protein expression of EE group significantly increased（P 〈0.05）, but mRNA and protein expression of MRP2 and MRPS, as well as GSH were significantly decreased（P 〈0.01, P 〈0.001 ）. After the glutathione treatment, placenta MRP1 mRNA and protein expression was significantly down - regulated （ P 〈 0.05 ） , while placenta MRP2 and MRP5 mRNA and protein expression were significantly up - regulated （P 〈 0.05 ）, GSH increased noticeably. Conclusion MRP - GSH transportation system exists in the placenta; glutathione can influence the bile acid transportation to treat rat intrahepatic cholestasis disease of pregnancy by regulating the placenta MRP - GSH transportation system.

关 键 词：雌激素 妊娠 肝内胆汁淤积 多药耐药相关蛋白 谷胱甘肽 

分 类 号：R714.255[医药卫生—妇产科学]