雌激素与孕鼠肝内胆汁淤积症实验研究

目的　探讨妊娠期肝内胆汁淤积症 (ICP)的发病机理及其雌激素诱导ICP的最适剂量。方法　选择孕 15天SD大鼠 80只 ,随机分成 4组 (每组 2 0只 )。高、中、低剂量实验组分别肌肉注射苯甲酸雌二醇 5 .0、2 .5、1.2mg/kg·d-1,连续 5d ;对照组不需特殊处理。每组各 10只鼠在用药前、处死前 ,取血检测生化指标 ,并于分娩后取肝脏及胎盘光镜及电镜标本 ,其余每组各 10只 ,孕鼠待其自然分娩后距停用药 7d时取血标本和肝脏光、电镜标本。结果　用药后低、高、中剂量实验组孕鼠血生化指标明显改变 (P <0 .0 1) ,而对照组用药前后上述指标无明显变化 ;实验组孕鼠肝脏和胎盘随着用药剂量的增加 ,类人类ICP样病理改变进行性加重 ,但高剂量实验组在产后距停药 1周时生化指标及肝脏的病理改变均未能恢复到正常状态时。结论　用苯甲酸雌二醇处理孕鼠可诱导孕鼠类人类ICP改变 ,以 2 .5mg/kg·d-1剂量组最接近人类ICP的发病经过和病理改变 ,随雌激素剂呈增加病变越趋严重 ,最终可能出现不可逆病变。

An Experimental Study of Estrogen and Liver Bile Fill up of Pregnant Rats

Objective To explore the pathogenesis of intrahepatic cholestasis of pregnancy (ICP) and determine the most suitable dosage for estrogen inducement. Methods 80 SD rats that had been pregnant for 15 days were chosen and divided them into 4 groups (20 rats of each group) by random. 5.0, 2.5 and 1.2mg/kg·d -1 of benzestrofol were intramuscularly injected to rats in the high, moderate and low dosage groups respectively for 5 consecutive days. No special treatment was required for the control group. Blood tests for biochemical criterion were conducted in ten rats of each group before medicine application and being put to death. Specimens of liver and placenta for light and electron microscope were taken after delivery. Specimens of liver and placenta for light and electron microscope were taken after natural delivery and 7 days after stop using drugs for the 10 rats of the rest groups. Results There were obvious changes in the blood biochemical criterion of pregnant rats of the low, moderate and high dosage groups (P<0.01) whereas no significant changes in the control group were found. As the medicine dosages given to the rats of the medicine administration group increased, the analogous human ICP of the livers and placentas experienced a progressive pathological change process. The biochemical criterion and the liver pathological changes of the high dosage group did not restore to normal state. Conclusion Benzestrofol can induce Analogous human ICP changes in pregnant rats. The 2.5 mg/kg·d -1 reflected the most of the human ICP invasion and pathological changes. As the estrogen dosages increases pathology becomes more severe and may finally lead to irreversible pathology.