[1]周婷婷,王　慧,南　燕,等.雌激素、孕激素及雌激素联合孕激素诱导中孕期大鼠胆汁淤积症模型的比较[J].新乡医学院学报,2017,34(5):369-373.[doi:10.7683/xxyxyxb.2017.05.006]
　ZHOU Ting-ting,WANG Hui,NAN Yan,et al.Comparison of the rat models of cholestasis during middle pregnancy induced by estrogen,progesterone and estrogen combined with progesterone[J].Journal of Xinxiang Medical University,2017,34(5):369-373.[doi:10.7683/xxyxyxb.2017.05.006]
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雌激素、孕激素及雌激素联合孕激素诱导中孕期大鼠胆汁淤积症模型的比较
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《新乡医学院学报》[ISSN:1004-7239/CN:41-1186/R]

卷:
34
期数:
2017年5
页码:
369-373
栏目:
基础研究
出版日期:
2017-05-05

文章信息/Info

Title:
Comparison of the rat models of cholestasis during middle pregnancy induced by estrogen,progesterone and estrogen combined with progesterone
作者:
周婷婷; 王　慧; 南　燕; 陈　帆; 李玉洁
（新乡医学院第三附属医院妇产科，河南　新乡　453003)
Author(s):
ZHOU Ting-ting; WANG Hui; NAN Yan; CHEN Fan; LI Yu-jie
(Department of Gynaecology and Obstetrics,the Third Affiliated Hospital of Xinxiang Medical University,Xinxiang 453003,Henan Province,China)
关键词:
雌激素; 孕激素; 妊娠期肝内胆汁淤积症
Keywords:
estrogen; progesterone; intrahepatic cholestasis of pregnancy
分类号:
R-332；Q95-33
DOI:
10.7683/xxyxyxb.2017.05.006
文献标志码:
A
摘要:
目的　应用雌激素、孕激素、雌激素+孕激素诱导建立中孕期大鼠肝内胆汁淤积症模型，并对3种模型进行比较，选出妊娠期肝内胆汁淤积症（ICP）研究的适宜模型。方法　取孕10 d 的Sprauge-Dawley大鼠40只，随机分为对照组、雌激素组、孕激素组和雌激素+孕激素组，每组10只，妊娠第10～14天，分别给予生理盐水、苯甲酸雌二醇、黄体酮、苯甲酸雌二醇+黄体酮注射液诱导动物模型，于用药前后分别检测各组大鼠血清丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)、碱性磷酸酶(ALP)、总胆酸(TBA)水平；测各组胎鼠体质量、死胎率；苏木精-伊红染色观察肝脏病理学变化。结果　对照组大鼠肝细胞及肝小叶形态结构正常，无明显病理改变；雌激素组大鼠肝细胞水肿明显，细胞质疏松，细胞大量脂肪变性，点状坏死较多，肝血窦变窄，胆管扩张且有胆汁淤积；孕激素组大鼠汇管区部分肝细胞水肿，少量脂肪变性细胞出现，毛细胆管扩张及部分炎性细胞浸润；雌激素+孕激素组大鼠肝细胞出现大量脂肪变性及点状坏死，炎性细胞浸润较多，部分可见胆栓形成。各组大鼠用药前血清ALT、AST、ALP、TBA水平比较差异均无统计学意义（P>0.05）。用药后，雌激素组、孕激素组、雌激素+孕激素组大鼠血清ALT、AST、ALP、TBA水平均较用药前显著升高（P<0.05），且高于对照组（P<0.05）；与雌激素组比较，孕激素组大鼠血清ALT、AST、ALP、TBA水平明显降低（P<0.05），雌激素+孕激素组大鼠血清ALT、AST、ALP、TBA水平明显升高（P<0.05）；与孕激素组比较，雌激素+孕激素组大鼠血清ALT、AST、ALP、TBA水平升高显著（P<0.05）。对照组、雌激素组、孕激素组大鼠的死胎率比较差异均无统计学意义（P>0.05），雌激素+孕激素组大鼠的死胎率与对照组、雌激素组、孕激素组比较均显著升高（P<0.05）。对照组、雌激素组、孕激素组胎鼠的体质量比较差异均无统计学意义（P>0.05），雌激素+孕激素组胎鼠的体质量与对照组、雌激素组、孕激素组比较均显著下降（P<0.05）。结论　雌激素、孕激素、雌激素+孕激素均有诱导大鼠胆汁淤积的作用，采用孕激素给药方式能够建立更符合ICP研究的中孕期大鼠胆汁淤积症模型。
Abstract:
Objective　To establish the rat models of cholestasis during middle pregnancy induced by estrogen,progesterone and estrogen combined with progesterone,and select a suitable model for intrahepatic cholestasis of pregnancy (ICP) by comparing the three models.Methods　Forty Sprauge-Dawley rats with pregnancy for 10 days were randomly divided into control group,estrogen group,progestogen group and estrogen+ progestogen group;ten rats in each group.The rat models were induced by injecting with physiological saline,estradiol benzoate,progesterone,estradiol benzoate combined with progesterone on the tenth day to the fourteenth day after pregnancy.The levels of serum alanine transarninase(ALT),aspartate aminotransferase(AST),alkaline phosphatase(ALP) and total bile acid(TBA) were detected before and after medication.The body weight and fetal death rate were measured.The pathological changes of liver were observed by hematoxylin eosin staining.Results　The morphology and structure of hepatocytes and hepatic lobules of rats in control group were normal,and there was no obvious pathological change.The pathological changes of hepatic tissues of rats in the estrogen group included the hepatocellular edema,loose cytoplasm,much cellular steatosis,more spotty necrosis,hepatic sinusoid narrowing,bile duct dilatation and cholestasis.The pathological changes of hepatic tissues of rats in the progesterone group included some hepatocellular edema in hepatic portal area,a few cellular steatosis,cholangiectasis and inflammatory cell infiltrate.There were a lot of fatty degeneration,spotty necrosis,inflammatory cell infiltration and some bile thrombus in hepatic cells of rats in the estrogen+progesterone group.There was no significant difference in serum ALT,AST,ALP and TBA levels among the four groups before medication(P>0.05).The levels of serum ALT,AST,ALP and TBA after medication were significantly higher than those before medication in the estrogen group,progesterone group,estrogen+progesterone group (P<0.05).The levels of serum ALT,AST,ALP and TBA in the estrogen group,progesterone group,estrogen+progesterone group were significantly higher than those in the control group after medication (P<0.05).Compared with the estrogen group,the levels of serum ALT,AST,ALP and TBA significantly decreased in the progesterone group (P<0.05);and they increased significantly in the estrogen+progesterone group (P<0.05).The levels of serum ALT,AST,ALP and TBA in the estrogen+progesterone group were significantly higher than those in the progesterone group (P<0.05).There was no significant difference in fetal death rate among the control group,estrogen group and progesterone group (P>0.05).The fetal death rate of rats in the estrogen+progesterone group was significantly higher than that in the control group,estrogen group and progesterone group (P<0.05).There was no significant difference in body weight of the fetal rats among the control group,estrogen group and progesterone group (P>0.05).The body weight of the fetal rats in the estrogen+progesterone group was significantly lower than that in the control group,estrogen group and progesterone group (P<0.05).Conclusion　Estrogen,progesterone,estrogen+progesterone can induce cholestasis in rats.The model of cholestasis in middle pregnancy rats could be established by progesterone,which is more suitable for ICP study.

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更新日期/Last Update: 2017-05-05