Müller D, Glöckner R, Rost M, Steinmetzer P
Institute of Pharmacology and Toxicology, Friedrich Schiller University Jena, Germany.
Exp Toxicol Pathol. 1998 Sep;50(4-6):507-13. doi: 10.1016/S0940-2993(98)80042-0.
Precision-cut rat liver slices (KRUMDIECK slicer, slice thickness 200-250 microm) were incubated in rollers containing modified William's medium E at 37 degrees C for 2, 24 and 48 hrs. Protein, DNA, potassium and glutathione concentrations did not decrease during 48 hrs. Lactate dehydrogenase (LDH) leakage into the medium was relatively marked during the first 2 hrs of incubation, from the 2nd to the 48th hr LDH leakage was very low. The same is true of the release of thiobarbituric acid-reactive substances. Albumin synthesis and transport into the medium decreased to about 70% after 48 hrs. Cytochrome P450 (CYP)-dependent 7-ethoxycoumarin O-deethylation rate was relatively stable up to 48 hrs, whereas testosterone hydroxylation decreased significantly without alterations of the proportions of the 7 quantified hydroxylated metabolites. After exposure of the slices to beta-naphthoflavone for 6 hrs CYP1A1-mRNA expression, measured by competitive RT-PCR, was increased by a factor of at least 1000. Precision-cut liver slices are a useful tool for the study of various hepatic functions, drug metabolism and its induction in vitro.
使用精密切片机（KRUMDIECK切片机，切片厚度200 - 250微米）切取大鼠肝脏切片，将其置于含有改良E型威廉姆斯培养基的滚瓶中，于37℃孵育2、24和48小时。在48小时内，蛋白质、DNA、钾和谷胱甘肽的浓度没有下降。在孵育的最初2小时内，乳酸脱氢酶（LDH）漏入培养基的情况较为明显，从第2小时到第48小时，LDH的泄漏量非常低。硫代巴比妥酸反应性物质的释放情况也是如此。48小时后，白蛋白的合成及向培养基中的转运下降至约70%。细胞色素P450（CYP）依赖的7 - 乙氧基香豆素O - 脱乙基速率在48小时内相对稳定，而睾酮羟化显著降低，且7种定量羟化代谢产物的比例没有改变。将切片用β - 萘黄酮处理6小时后，通过竞争性逆转录 - 聚合酶链反应（RT - PCR）检测发现，CYP1A1 - mRNA表达增加了至少1000倍。精密肝脏切片是研究各种肝功能、药物代谢及其体外诱导作用的有用工具。
