Institute of 1st Surgical Clinic, University of Milan School of Medicine, Milan, Italy.
Biochem Pharmacol. 1980 Mar 1;29(5):677-80. doi: 10.1016/0006-2952(80)90537-7.
In the search for an animal model suitable for the study of ethinyl estradiol (EE) induced alterations of bile secretion, we have investigated the effects of three different doses (50-500-5000 microg/kg body wt., orally for 10 days) of EE on bile flow and composition and on liver microsomal mixed function oxidase system in female Albino-Swiss mice. No difference of bile flow was found between control and EE-treated mice. The decrease of bile acid secretion was dose-related and significant in animals treated with 500 and 5000 microg/kg of EE. Cholesterol output was similar in control and EE-treated animals. The molar ratio of bile acid to biliary cholesterol was significantly lower in all groups of EE-treated mice as compared with controls. The specific activities of 3,4-benzpyrene hydroxylase, aniline hydroxylase and NADPH cytochrome-c-reductase, as well as the content of cytochromes P-450 and b(5) decreased proportionally, in a dose dependent manner and significantly after 500 and 5000 microg/kg of EE. Our data indicate that mice, following EE, develop a lithogenic bile without obvious cholestasis. Moreover, they demonstrate a decrease of liver microsomal enzyme activities and cytochromes and suggest a relationship between the impairment of liver microsomal mixed function oxidase system and the changes of bile lipid composition.
在寻找适合研究雌二醇（EE）诱导的胆汁分泌改变的动物模型时，我们研究了三种不同剂量（50-500-5000μg/kg 体重，口服 10 天）的 EE 对雌性白化瑞士小鼠胆汁流量和成分以及肝微粒体混合功能氧化酶系统的影响。在对照组和 EE 处理组的小鼠之间，胆汁流量没有差异。在接受 500 和 5000μg/kg EE 治疗的动物中，胆汁酸分泌的减少呈剂量相关性且具有统计学意义。胆固醇的分泌在对照组和 EE 处理组的动物中相似。与对照组相比，所有 EE 处理组的小鼠胆汁酸与胆汁胆固醇的摩尔比均显著降低。3,4-苯并芘羟化酶、苯胺羟化酶和 NADPH 细胞色素 c 还原酶的比活性以及细胞色素 P-450 和 b(5)的含量均以剂量依赖的方式显著降低，在接受 500 和 5000μg/kg EE 后显著降低。我们的数据表明，EE 处理后的小鼠产生了一种无明显胆汁淤积的成石性胆汁。此外，它们还显示出肝微粒体酶活性和细胞色素的降低，并提示肝微粒体混合功能氧化酶系统的损害与胆汁脂质组成的变化之间存在关系。
