地塞米松对乙炔雌二醇诱发的肝内胆汁淤积症孕鼠儿茶酚氧位甲基转移酶活性、胎盘和肝脏组织雌激素受体表达的影响  

Effects of dexamethazone on the activity of catechol-o-methyltransferase and the expression of estrogen receptor in pregnant rats with ethinyl estradiol-induced intrahepatic cholestasis

作　　者：喻玲[1] 赵莹[1] 丁依玲[1] 

机构地区：[1]中南大学湘雅二医院妇产科,长沙410011

出　　处：《国际病理科学与临床杂志》2010年第4期282-290,共9页Journal of International Pathology and Clinical Medicine

摘　　要：目的:研究地塞米松对雌激素诱发的肝内胆汁淤积症孕鼠儿茶酚氧位甲基转移酶(catechol-O-methyl-transferase,COMT)活性及肝脏和胎盘雌激素受体(estrogen receptor,ER)表达的影响,探讨地塞米松治疗妊娠期肝内胆汁淤积症(intrahepatic cholestasis of pregnancy,ICP)的作用机制。方法:选择SD孕鼠随机分为ICP对照组(A组)、ICP地塞米松干预组(B组)、非ICP对照组(C组)、非ICP地塞米松干预组(D组)。4组孕鼠均于见到阴道血性分泌物后剖腹取胎,计量胎鼠身长、体质量,计算死胎数量。光镜下观察各组孕鼠胎盘和肝脏组织病理学改变,并采用免疫组织化学法检测其ER的表达;采用高效液相色谱法检测各组孕鼠COMT的活性浓度;采用放射免疫法检测孕鼠血清游离雌三醇(unconjugated estriol,uE3)浓度。结果:(1)4组胎鼠中,死胎率A组高于B组和C组,差异有统计学意义(P<0.01)。(2)A组胎鼠身长和体质量低于B组和C组,差异有统计学意义(P<0.01),D组显著低于C组(P<0.01)。(3)4组孕鼠肝脏和胎盘组织病变积分结果比较,A组显著高于B组和C组,差异有统计学意义(P<0.01),C组与D组比较,差异无统计学意义(P>0.05)。(4)孕鼠胎盘组织中ER主要分布于细胞浆内,少数在细胞核内表达,肝脏组织中ER主要分布在细胞膜上。4组孕鼠ER表达的平均光密度值比较,A组高于B组和C组,D组低于C组,差异均有统计学意义(均P<0.01)。(5)孕鼠红细胞COMT活性浓度比较,B组和C组均高于A组,D组高于C组,差异均有统计学意义(均P<0.01)。(6)孕鼠血清uE3浓度比较,B组和C组均低于A组,D组低于C组,差异均有统计学意义(均P<0.01)。(7)COMT活性浓度与uE3水平呈负相关(r=-0.381,P<0.05)。结论:地塞米松对雌激素诱发的肝内胆汁淤积的孕鼠具有保护作用,并能改善胎鼠预后,其机制与对孕鼠胎盘及肝脏细胞ER的表达及肝脏COMT活性浓度的调节作用有关。Objective To examine the effects of dexamethasone（DXM） on the activity of catechol-o-methyltransferase（COMT）,the expression of estrogen receptor（ER） in liver and placenta in pregnant rats with ethinylestradiol-induced intrahepatic cholestasis and the underlying mechanisms.Methods Forty healthy SD female rats were randomly divided into 4 groups：a control group of intrahepatic cholestasis of pregnancy（ICP）（Group A）,an intervention group of ICP（Group B）,a control group of non-ICP（Group C） and an intervention group of non-ICP（Group D）.All rats were carried out caesarean section when blood secretion was seen in the vagina.The amount of dead fetus,the length and weight of all fetus were recorded.The placenta and liver of pregnant rats were pathologically examined under light microscope.Immunohistochemistry was applied to determine the ER expression in the placenta and liver.The COMT activity in maternal erythrocyte were analyzed by highly effective liquid chromatography,and the maternal serum levels of unconjugated estriol（uE3） were measured by radioimmunoassay.Results （1）The fetal death rate in Group A was significantly higher than that in Group B and Group C（P〈0.01）.（2）The fetal length and weight in Group A were significantly lower than that in Group B and Group C（P〈0.01）.The fetal length and weight in Group D were significantly lower than those in Group C（P〈0.01）.（3）The necrosis area of liver or placenta in Group A was significantly higher than those in Group B and Group C（P〈0.01）,whereas the difference between Group C and Group D was not significant（P〈0.05）.（4） In placenta,most of the positive signal of ER expression was located in cytoplasm whereas a small part is in the cell nuclear;in liver,the positive signal of ER expression was located on the membrane.The expression of ER in placental and liver in Group A was significantly higher than that in Group B and Group C（P〈0.01）.The expression of ER in Group D was lower than that

关 键 词：地塞米松 胆汁淤积 雌激素受体 儿茶酚氧位甲基转移酶 

分 类 号：R96[医药卫生—药理学]