Matuskova Zuzana, Tunkova Alena, Anzenbacherova Eva, Vecera Rostislav, Siller Michal, Tlaskalova-Hogenova Helena, Zidek Zdenek, Anzenbacher Pavel
Department of Pharmacology, Faculty of Medicine and Dentistry, Palacky University, Olomouc, Czech Republic.
Neuro Endocrinol Lett. 2010;31 Suppl 2:46-50.
The aim of the study was to find whether probiotic Escherichia coli Nissle 1917 O6:K5:H1 (EcN) influences the expression of cytochromes P450 (CYP) in the rat intestine.
Live bacterial suspension of EcN was administered to healthy male Wistar rats daily for 7 days. Control group of rats was stressed by oral application of the saline solution daily for 7 days as well. Sections of the duodenum, jejunum, ileum, caecum and colon have been taken from each experimental animal. With all individual samples, microsomal fraction has been prepared and expression of selected CYPs was determined by Western blotting. The levels of expression of CYPs were also evaluated by mRNA using real-time PCR.
It was found that there are changes in expression of CYP enzymes studied along the intestine. CYP1A1, 2B1/2 and 2E1 are present mainly in the duodenum and jejunum; on the other hand, CYP2C6 is expressed mainly in the caecum and colon. CYP3A was found all over the rat intestine. The results show that there are no prominent differences between control samples and samples with EcN, only the expression of CYP3A protein in the duodenum appears to exhibit a clear tendency to decrease. In the case of the colon, a significant increase in the expression of CYP3A (most likely CYP3A1) after treatment of rats with EcN was found.
This in vivo study revealed that the levels of colon CYP3A could be significantly increased in rats treated with probiotic EcN. On the contrary, the expression of CYP3A in the duodenum decreased. However, the changes in the expression of CYP enzymes are probably not as extensive to be clinically important in man; hence, most likely the probiotic EcN has little influence on the intestinal drug metabolism by CYP enzymes.
本研究旨在探究益生菌大肠杆菌Nissle 1917 O6:K5:H1（EcN）是否会影响大鼠肠道中细胞色素P450（CYP）的表达。
将EcN的活菌悬液每日给予健康雄性Wistar大鼠，持续7天。对照组大鼠也每日口服生理盐水7天以造成应激。从每只实验动物身上采集十二指肠、空肠、回肠、盲肠和结肠的组织切片。针对所有个体样本，制备微粒体组分，并通过蛋白质免疫印迹法测定所选CYP的表达。还使用实时聚合酶链反应通过mRNA评估CYP的表达水平。
研究发现，所研究的CYP酶在肠道中的表达存在变化。CYP1A1、2B1/2和2E1主要存在于十二指肠和空肠；另一方面，CYP2C6主要在盲肠和结肠中表达。在大鼠整个肠道中均发现有CYP3A。结果表明，对照样本与含EcN的样本之间没有显著差异，仅十二指肠中CYP3A蛋白的表达似乎呈现出明显的下降趋势。在结肠中，发现用EcN处理大鼠后CYP3A（很可能是CYP3A1）的表达显著增加。
这项体内研究表明，用益生菌EcN处理的大鼠结肠中CYP3A水平可能会显著增加。相反，十二指肠中CYP3A的表达下降。然而，CYP酶表达的变化可能在临床上对人类并不具有重要意义；因此，益生菌EcN很可能对CYP酶的肠道药物代谢影响很小。
