Intestinal flora induces the expression of Cyp3a in the mouse liver
Intestinal flora induces the expression of Cyp3a in the mouse liver
复制标题
DOI：
10.1080/00498250802651984
复制
发表时间：
2009-01-01
期刊：
影响因子：
1.8
通讯作者：
Sugiyama, K.
中科院分区：
文献类型：
--
作者：
Toda, T.;Saito, N.;Sugiyama, K.
为探讨肠道植物群对细胞色素P450（CYP450，CYP450）表达的影响，比较了无特定病原体（SPF）和无菌（GF）小鼠CYP450 mRNA的表达。与GF小鼠相比，SPF小鼠肝脏中的大多数主要同工酶的表达量较高。核因子如PXR和组成型雄烷受体（CAR），以及参与石胆酸（LCA）解毒的转运蛋白和结合酶，也在SPF小鼠中显示出较高的表达。研究结果表明，在SPF小鼠的肝脏中，肠道植物群产生的LCA通过激活PXR和CAR增加CYP的表达。抗生素等药物、某些疾病和衰老等已知会改变肠道植物群。目前的研究结果表明，这种变化也会影响药物代谢，是药代动力学个体差异的因素之一。
In order to determine the effects of intestinal flora on the expression of cytochrome P450 (CYP), the mRNA expression of CYP was compared between specific pathogen-free (SPF) and germ-free (GF) mice. Most of the major CYP isozymes showed higher expression in the livers of SPF mice compared with GF mice. Nuclear factors such as pregnane - receptor (PXR) and constitutive androstane receptor (CAR), as well as transporters and conjugation enzymes involved in the detoxification of lithocholic acid (LCA), also showed higher expression in SPF mice. The findings suggest that in the livers of SPF mice, LCA produced by intestinal flora increases the expression of CYPs via activation of PXR and CAR. Drugs such as antibiotics, some diseases and ageing, etc. are known to alter intestinal flora. The present findings suggest that such changes also affect CYP and are one of the factors responsible for individual differences in pharmacokinetics.