Gene expression profiles from livers of ethinylestradiol- and chlorpromazine-treated C57BL6/mice after 25 days. Mus musculus

Toxicogenomics is used as a tool to identify mechanisms and markers of cholestasis in C57BL/6 mice treated by oral gavage using ethinylestradiol(EE2) and chlorpromazine (CPZ). A 25 day dose range finding study was performed, which resulted in no changes in clinical chemistry (serum cholesterol, total bile acids, and total bilirubin) or histopathology (hepatocyte vacuolization). Whole genome expression profiling of the liver was assessed after 25 days of repeated exposure with 10 mg/kg bw for CPZ and 3.70 mg/kg bw for EE2. Overall design: 10 samples were analyzed per compound; 5 for the time-matched vehicle and 5 for the treatment. There are 20 samples in total. EE2 and CPZ were dissolved in sunflower oil and PBS, respectively.

本研究借助毒理基因组学（Toxicogenomics）技术，旨在识别经口服灌胃给予乙炔雌二醇（ethinylestradiol, EE2）与氯丙嗪（chlorpromazine, CPZ）的C57BL/6小鼠的胆汁淤积发病机制与生物标志物。本研究开展了为期25天的剂量范围探索实验，结果显示，受试小鼠的临床生化指标（血清胆固醇、总胆汁酸及总胆红素）与组织病理学特征（肝细胞空泡变性）均未出现异常变化。在以10 mg/kg体重剂量重复给予CPZ、3.70 mg/kg体重剂量重复给予EE2并持续25天后，对小鼠肝脏开展全基因组表达谱分析。实验设计：每种受试化合物设置10个样本，其中5个为时间匹配的溶剂对照组，5个为处理组，总计20个样本。EE2与CPZ分别溶解于葵花籽油与磷酸盐缓冲液（PBS）中。