乙炔雌二醇诱发孕鼠肝内胆汁淤积

Ethinylestradiol Induced Intrahepatic Cholestasis in Pregnant Rats

目的 探讨乙炔雌二醇 (EE)在妊娠期肝内胆汁淤积症 (ICP)发病中的作用。 方法 选择孕 15 d的清洁级 SD大鼠 2 0只 ,随机分为观察组和对照组 ,分别皮下注射 EE的丙二醇溶液 2 .5mg.Kg- 1 .d- 1 和 1,2 -丙二醇 (PG) ,连续 5 d。两组分别在用药前及用药后 3d和 5 d检测血谷丙转氨酶(AL T)、谷草转氨酶 (AST)、碱性磷酸酶 (AL P)、总胆酸 (TBA )、胆固醇 (CHO)和甘油三酯 (TG)的变化 ,同时观察肝脏的形态学改变及胎仔的生长发育情况。 结果 用药后观察组的孕鼠血 AL T、AL P、AST及 TBA明显升高 (P<0 .0 5 ) ;血 CHO和 TG用药后明显下降 (P<0 .0 5 ) ,而对照组上述生化指标用药前后无明显变化 (P>0 .0 5 ) ;观察组孕鼠肝脏在光镜和电镜下均见毛细胆管内胆汁酸沉积 ,而对照组肝脏无类似改变。观察组胎仔的体重、身长、尾长较对照组明显小 (P<0 .0 5 ) ;观察组大鼠孕期为 19d,而对照组大鼠孕期为 2 2 d,两者有明显差异 (P<0 .0 5 )。 结论 用 EE处理孕鼠可产生类似于人类 ICP的表现。

Objective To investigate the role of 17 α ethinylestradiol (EE) in the pathogenesis of intrahepatic cholestasis of pregnancy (ICP). Methods Twenty rats which were fourteen days pregnant were randomized divided into an observed group and a controlled group. The observed rats were administered EE at a dose of 2.5mg ·kg -1 ·d -1 subcutaneously for 5 days. The controlled rats received subcutaneous injection of the same volume of propylene glycol (PG) for 5 days. The levels of serum total bile salt (TBA), serum aminotransferases (ALT), alkaline phosphatases (ALP), aspartate transaminase (AST), cholesterol (CHO) and triglyceride (TG) were measured before the treatment, 3 and 5 days after the treatment respectively. The morphologic changes of the liver of the rats after delivery and the growth and development of the fetal rats were observed. Results In the observed group, the ALT, AST, ALP, TBA levels were significantly increased and the CHO,TG level were decreased significantly (P<0.05). There was dilated bile canaliculi with retention of finely granular biliary material under light and electronic microscope in the observed group. Body weight and length, tail length of fetal rats in the observed group were lighter and shorter than those of the controlled group (P<0.05). Conclusion The pregnant rats after the administration of EE can result in intrahepatic cholestasis, fetal rat growth restriction, which is like the ICP changes in human being.