Thörn Mari, Finnström Niklas, Lundgren Stefan, Rane Anders, Lööf Lars
Centre of Clinical Research, Uppsala University, Central Hospital, SE-721 89 Västerås, Sweden.
Ups J Med Sci. 2007;112(3):303-12. doi: 10.3109/2000-1967-203.
The aim of this study was to investigate the effect of inflammation on the gene expression of three cytochrome P450's (CYP) and P-glycoprotein (P-gp) in the rectal and colonic mucosa in patients with proctitis.
Biopsies were obtained from inflamed and normal mucosa in association with routine sigmoidoscopy in patients with proctitis. The biopsies were snap-frozen in liquid nitrogen. Real time PCR (polymerase chain reaction) was used for quantitative analyses of mRNA specific for the CYP2E1, CYP3A4 and CYP3A5 gene and the MDR1 genes. Values were normalised based on gene expression of beta-actin to enable comparisons between samples.
The gene expression of CYP2E1 and CYP3A4 was lower in mucosa with severe inflammation vs normal mucosa (p<0.05). For CYP3A5 and P-gp there was no significant difference when comparing normal and inflammatory changed mucosa.
Our study suggests that at least for some of the CYP enzymes the expression decreases in response to the inflammatory process in the gastrointestinal tract.
本研究旨在调查炎症对直肠炎患者直肠和结肠黏膜中三种细胞色素P450(CYP)和P-糖蛋白(P-gp)基因表达的影响。
在直肠炎患者进行常规乙状结肠镜检查时,从发炎黏膜和正常黏膜获取活检组织。活检组织在液氮中速冻。实时聚合酶链反应(PCR)用于对CYP2E1、CYP3A4和CYP3A5基因以及MDR1基因的特异性mRNA进行定量分析。基于β-肌动蛋白的基因表达对数值进行标准化,以便在样本之间进行比较。
与正常黏膜相比,严重炎症黏膜中CYP2E1和CYP3A4的基因表达较低(p<0.05)。比较正常黏膜和炎症改变的黏膜时,CYP3A5和P-gp没有显著差异。
我们的研究表明,至少对于某些CYP酶,其表达会因胃肠道的炎症过程而降低。