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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 study the effect of dexamethasone on the activity of catechol-O-methyl-transferase (COMT) and the effects of estrogen receptor on liver and placenta in estrogen-induced intrahepatic cholestasis , ER) expression, and explore the mechanism of dexamethasone in the treatment of intrahepatic cholestasis of pregnancy (ICP). Methods: Pregnant SD rats were randomly divided into ICP control group (A group), ICP dexamethasone intervention group (B group), non-ICP control group (C group) and non-ICP dexamethasone intervention group (D group). 4 groups of pregnant rats were seen after vaginal bloody discharge cesarean section fetus, measurement fetal body length, body weight, calculate the number of stillbirth. The pathological changes of placenta and liver in each group were observed under light microscope, and the expression of ER was detected by immunohistochemical method. The activity of COMT in each group was detected by high performance liquid chromatography (HPLC) Rat serum free estriol (unconjugated estriol, uE3) concentration. Results: (1) The stillbirth rate of group A was higher than that of group B and C (P <0.01). (2) The body length and body weight of fetal rats in group A were lower than those in group B and C (P <0.01), and those in group D were significantly lower than those in group C (P <0.01). (3) Compared with group B and group C, the difference of liver and placental tissue lesion scores in 4 groups of pregnant rats was statistically significant (P <0.01). There was no significant difference between group C and group D (P> 0.05). (4) ER in placenta of pregnant rats mainly distributed in the cytoplasm, few in the nucleus, ER in the liver mainly distributed in the cell membrane. Compared with group B and group C, the average optical density of ER expression in the four groups of pregnant rats was significantly lower than that in group C (all P <0.01). (5) The concentrations of COMT in pregnant rat erythrocytes were higher than those in group A and B (P <0.01). The difference was statistically significant (P <0.01). (6) The levels of uE3 in pregnant rats were lower than those in group A and group D, respectively (all P <0.01). (7) The concentration of COMT was negatively correlated with the level of uE3 (r = -0.381, P <0.05). Conclusion: Dexamethasone can protect estrogen-induced intrahepatic cholestasis in pregnant rats and improve the prognosis of fetal rats. The mechanism of dexamethasone is related to the expression of ER in placental and hepatic cells and the regulation of hepatic COMT activity in pregnant rats .