Ejiri Noriko, Katayama Kei-Ichi, Kiyosawa Naoki, Baba Yasuko, Doi Kunio
Department of Veterinary Pathology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan.
Exp Mol Pathol. 2005 Dec;79(3):272-7. doi: 10.1016/j.yexmp.2005.08.002. Epub 2005 Oct 11.
We previously reported the expression profiles of 9 cytochrome P450 isozymes (CYPs) proteins and those of 40 CYPs genes in pregnant rat's liver, placenta and fetal liver after treatment with pregnenolone-16alpha-carbonitrile (PCN) or phenobarbital (PB). This study was carried out focusing on the gene expression profiles of Phase II drug metabolizing enzymes, Glutathione S-transferase isozymes (GSTs) and UDP-glycosyltransferase isozymes (UDPGTs). Fischer 344 (F344) pregnant rats were daily treated intraperitoneally with 50 mg/kg of PCN or 80 mg/kg of PB from 13 to 16 days of gestation (DG). They were sacrificed on 17 DG, and microarray analysis using Affymetrix Rat Expression Array 230 A was performed. Among 16 GSTs genes examined in this study, 7 genes were significantly induced in dam's liver and 3 genes in fetal liver, respectively, in the PCN-group, while 8 genes were significantly induced in dam's liver and 1 gene in fetal liver, respectively, in the PB-group. On the other hand, among 11 UDPGTs genes examined, 5 genes were significantly induced in dam's liver and 3 genes in fetal liver, respectively, in the PCN-group, while 5 genes were significantly induced in dam's liver and 1 gene in fetal liver, respectively, in the PB-group. There were no significant changes in the placenta of all groups. This is the first report of the gene expression profiles of Phase II drug metabolizing enzymes in pregnant rat and fetal livers and placenta after treatment with typical inducers of drug metabolizing enzymes.
我们之前报道了孕烯醇酮-16α-腈（PCN）或苯巴比妥（PB）处理后，妊娠大鼠肝脏、胎盘和胎儿肝脏中9种细胞色素P450同工酶（CYPs）蛋白及40种CYPs基因的表达谱。本研究聚焦于Ⅱ相药物代谢酶、谷胱甘肽S-转移酶同工酶（GSTs）和尿苷二磷酸糖基转移酶同工酶（UDPGTs）的基因表达谱。将Fischer 344（F344）妊娠大鼠在妊娠第13至16天每天腹腔注射50 mg/kg的PCN或80 mg/kg的PB。在妊娠第17天处死大鼠，并使用Affymetrix大鼠表达芯片230 A进行微阵列分析。在本研究检测的16种GSTs基因中，PCN组母鼠肝脏中有7种基因显著诱导，胎儿肝脏中有3种基因显著诱导；而PB组母鼠肝脏中有8种基因显著诱导，胎儿肝脏中有1种基因显著诱导。另一方面，在检测的11种UDPGTs基因中，PCN组母鼠肝脏中有5种基因显著诱导，胎儿肝脏中有3种基因显著诱导；PB组母鼠肝脏中有5种基因显著诱导，胎儿肝脏中有1种基因显著诱导。所有组的胎盘均无显著变化。这是关于用典型药物代谢酶诱导剂处理后妊娠大鼠、胎儿肝脏和胎盘Ⅱ相药物代谢酶基因表达谱的首次报道。
