血红素加氧酶1在妊娠期肝内胆汁淤积症孕鼠肝脏组织和胎鼠脑组织中的表达及其意义

doi:10.7694/jldxyxb20130417

吉林大学学报(医学版)

血红素加氧酶1在妊娠期肝内胆汁淤积症孕鼠肝脏组织和胎鼠脑组织中的表达及其意义

李红霞¹，刘伯锋²，姚珍薇³，邵勇^3

1.延安大学附属医院妇科，陕西延安 716000；2.延安大学医学院解剖学教研室，陕西延安 716000；3.重庆医科大学第一附属医院妇产科，重庆 400016

收稿日期:2012-12-17 出版日期:2013-07-28 发布日期:2013-08-17
通讯作者: 刘伯锋（Tel:0911-2416893，E-mail:lihx66@163.com） E-mail:lihx66@163.com
作者简介:李红霞（1972-），女，陕西省延安市人，副主任医师，医学硕士，主要从事妇科内分泌学研究。
基金资助:
重庆市卫生局科研基金资助课题（2009-2-386）

Expressinons of heme oxygenase-1 in liver tissue of pregnant rats with intrahepatic cholestasis of pregnancy and brain tissue of fetal rats and significance

LI Hong-xia¹,LIU Bo-feng²,YAO Zhen-wei³,SHAO Yong³

1. Department of Gynecology,Affiliated Hospital，Yan’an University,Yan’an 716000,China；2.Department of Anatomy,Medical College，Yan’an University,Yan’an 716000，China；3.Department of Obstetrics and Gynecology,First Affiliated Hospital,Chongqing University of Medical Sciences，Chongqing 400016，China

Received:2012-12-17 Online:2013-07-28 Published:2013-08-17

摘要/Abstract

摘要：

目的：建立肝内妊娠期胆汁淤积症（ICP）大鼠模型，检测血红素加氧酶1（HO-1）在ICP孕鼠肝脏组织及胎鼠脑组织中的表达,探讨ICP的发病机制。方法：40只孕鼠随机分为实验组和对照组，每组20只。从孕15 d起，实验组孕鼠每天后肢内侧皮下注射孕酮和雌二醇，对照组孕鼠注射精制植物油。至孕21 d断头取血检测生化指标；取出母鼠肝脏及胎鼠脑组织，HE染色观察其病理组织学变化；免疫组织化学和图像分析法检测脑海马CA1区HO-1表达水平。结果：与对照组比较，实验组孕鼠血清天冬氨酸氨基转移酶(AST)、丙氮酸氨基转移酶（ALT）和总胆汁酸（TBA）水平均明显升高(P<0.01)。病理组织学表现，实验组孕鼠部分肝细胞有颗粒变性和空泡变性，肝小叶结构正常；胎鼠脑组织疏松，空泡样变性明显，部分细胞溶解，甚至消失。对照组孕鼠肝脏和胎鼠脑组织无明显病理改变。免疫组织化学及图像分析结果，与对照组比较，实验组胎鼠脑组织HO-1免疫着色强度减弱，HO-1表达水平明显下降 (P<0.05)。结论: ICP胎鼠脑组织中HO-1表达下降，可能与ICP胎儿窘迫的不良结局有关。

关键词: 胆汁淤积, 肝内, 血红素加氧酶1, 雌激素, 孕激素, 胎鼠脑组织, 大鼠, SD

Abstract:

Abstract:Objective To establish intrahepatic cholestasis of pregnancy (ICP) models of rats and detect the expression of heme oxygenase-1(HO-1) in liver tissue of pregnant rats with ICP and brain tissue of fetal rats,and to explore the pathogenesis of ICP.Methods 40 pregnant rats were randomly divide into experiment group and control group,20 rats in each group. From the 15th day after pregnancy,the pregnant rats in experiment group were administered with estrogen and progestrone to induce ICP，while the rats in control group were administered with vegetable oil.At the 21st day after pregnancy the rats were executed and the blood samples were obtained to detect the biochemical indicators,and the pathologic changes in liver tissue of pregnant rats and brain tissue of fetal rats were observed by HE staining; the HO-1 expression in hippocampal CA1 section of brain tissue of fetal rats was detected by immunohistochemistry staining and image analysis. Results Compared with control group,the levels of serum alanine aminotransferas
es (ALT), total bile salt (TBA),aspartate amino transaminase(AST) of the pregnant rats in experiment group were significantly increased (P<0.01). The pregnant rats in experiment group showed granule and vacuolization,natural hepatic foliole structure in liver;and the structural changes such as swelling,vacuolar degeneration,partial cells dissolution,and disappearance in brain tissue of fetal rats were found;but there was no pathologic changes in control group. The immunohistochemistry staining and image analysis results showed that compared with control group,the number of HO-1 immunoreaction positive cells in brain tissue of fetal rats was significantly increased in experiment group,and the HO-1 expression level in experiment group was significantly decreased(P<0.05). Conclusion The expression of HO-1 in brain tissue of fetal rats with ICP is decreased,which suggests that HO-1 might be important to cause fetal anoxia and death.

Key words: cholestasis,intrahepatic, heme oxygenase-1; , estrogen, progesterone; , fetal brain, rats,SD

中图分类号:

R575.7

李红霞，刘伯锋，姚珍薇，邵勇. 血红素加氧酶1在妊娠期肝内胆汁淤积症孕鼠肝脏组织和胎鼠脑组织中的表达及其意义[J]. 吉林大学学报(医学版), 2013, 39(4): 726-729.

LI Hong-xia,LIU Bo-feng,YAO Zhen-wei,SHAO Yong. Expressinons of heme oxygenase-1 in liver tissue of pregnant rats with intrahepatic cholestasis of pregnancy and brain tissue of fetal rats and significance[J]. Journal of Jilin University Medicine Edition, 2013, 39(4): 726-729.

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血红素加氧酶1在妊娠期肝内胆汁淤积症孕鼠肝脏组织和胎鼠脑组织中的表达及其意义

Expressinons of heme oxygenase-1 in liver tissue of pregnant rats with intrahepatic cholestasis of pregnancy and brain tissue of fetal rats and significance

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