Diet and phenobarbital affect cholesterol homeostasis and drug metabolism

High cholesterol diet and xenobiotic treatment induce changes in cholesterol homeostasis and drug metabolism. Mice were either 7 days on high cholesterol diet or were treated with phenobarbital. Liver samples were analyzed using Sterolgene v0 cDNA microarrays. Sterolgene microarray is a tool designed to enable focused studies of cholesterol homeostasis and drug metabolism. We show that one week of cholesterol diet down-regulates cholesterol biosynthesis and up-regulates xenobiotic metabolism (Cyp3 family). Phenobarbital treatment also up-regulates xenobiotic metabolism (Cyp2b and Cyp3a families). We can conclude that the Sterolgene series of cDNA microarrays represent novel original tool, enabling focused and cost-wise studies of cholesterol homeostasis and drug metabolism. Keywords: Treatment and diet effects One group of mice was treated i.p. with 50 mg/kg of phenobarbital in vehicle (5% DMSO in corn oil). Untreated group was injected vehicle. Third group was 7 days on 1 % (w/w) cholesterol diet prior vehicle treatment. After 10 h animals were sacrificed and livers were stored. Pools of total RNA from two animals were mixed. Three pools of untreated and phenobarbital treated groups, and two pools of cholesterol diet group were co-hybridized with liver reference on Sterolgene v0 cDNA microarray. No dye-swaps were performed.

高胆固醇饮食与外源物处理可诱导胆固醇稳态及药物代谢发生改变。实验小鼠或接受为期7天的高胆固醇饮食，或予以苯巴比妥处理。采用Sterolgene v0 cDNA微阵列（Sterolgene v0 cDNA microarray）对肝脏样本进行分析。Sterolgene微阵列（Sterolgene microarray）是一款专为聚焦研究胆固醇稳态与药物代谢而开发的工具。本研究发现，为期7天的高胆固醇饮食可下调胆固醇生物合成通路，并上调外源物代谢通路（Cyp3家族）；苯巴比妥处理同样可上调外源物代谢通路（Cyp2b与Cyp3a家族）。综上可证，Sterolgene系列cDNA微阵列是一款全新原创工具，可实现胆固醇稳态与药物代谢的聚焦式、高性价比研究。
关键词：干预与饮食效应
一组小鼠以玉米油中5%二甲基亚砜（DMSO）为溶媒，予以50mg/kg剂量的苯巴比妥腹腔内（intraperitoneal, i.p.）注射处理；未处理组仅注射上述溶媒。第三组小鼠先接受为期7天的1%（重量/重量）高胆固醇饮食，随后予以溶媒处理。处理10小时后处死所有动物，采集肝脏样本并妥善保存。将每两只动物的总RNA混合为一个样本池：未处理组与苯巴比妥处理组各制备3个样本池，高胆固醇饮食组制备2个样本池，将上述样本池与肝脏参照样本共同在Sterolgene v0 cDNA微阵列上进行杂交。本实验未进行染料互换实验。