Changes in the expression of drug-metabolising enzymes and drug transporters in mice with collagen antibody-induced arthritis
Changes in the expression of drug-metabolising enzymes and drug transporters in mice with collagen antibody-induced arthritis
复制标题
胶原抗体诱导关节炎小鼠药物代谢酶和药物转运蛋白表达的变化
DOI：
10.1080/00498254.2022.2137442
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发表时间：
2022-07
期刊：
影响因子：
1.8
通讯作者：
Chieri Fujino;S. Ueshima;T. Katsura
中科院分区：
文献类型：
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作者：
Chieri Fujino;S. Ueshima;T. Katsura
摘要1.我们研究了药物代谢酶和药物转运蛋白在胶原抗体诱导的关节炎（CAIA）小鼠的肝脏，小肠和肾脏中表达的变化，以确定这些表达的变化是否影响类风湿关节炎患者的药物药代动力学。2. CAIA小鼠肝脏和小肠中细胞色素P450（Cyp）2b 10、Cyp 2c 29和Cyp 3a 11的mRNA表达水平低于对照小鼠。与对照组小鼠相比，CAIA小鼠肝脏多药耐药蛋白1 B、肽转运蛋白2和有机阴离子转运蛋白（Oat）2的mRNA表达水平升高。这些表达水平的变化在器官之间是不同的。然而，Oat 2 mRNA的表达升高与蛋白表达和转运活性的增加无关，使用[3 H]cGMP作为底物进行评价。3.这些结果表明，关节炎可以改变药代动力学相关基因的表达，但这种变化可能不一定与类风湿关节炎患者的药代动力学有关。Oat 2 mRNA表达水平与血浆IL-6水平呈正相关，提示Oat 2的转录激活可能发生在炎症状态。
Abstract 1. We investigated the changes in the expression of drug-metabolising enzymes and drug transporters in the liver, small intestine and kidney of mice with collagen antibody-induced arthritis (CAIA) to determine whether changes in these expressions affect pharmacokinetics of drugs in patients with rheumatoid arthritis. 2. mRNA expression levels of cytochrome P450 (Cyp) 2b10, Cyp2c29 and Cyp3a11 were observed to be lower in the liver and small intestine of CAIA mice than in control mice. Compared with control mice, mRNA expression levels of multidrug resistance 1 b, peptide transporter 2 and organic anion transporter (Oat) 2 were high in the liver of CAIA mice. Changes in these expression levels were different among organs. However, elevated expression of Oat2 mRNA was not associated with an increase in protein expression and transport activity evaluated using [3H]cGMP as a substrate. 3. These results suggest that arthritis can change the expression of pharmacokinetics-related genes, but the changes may not necessarily be linked to the pharmacokinetics in patients with rheumatoid arthritis. On the other hand, we found Oat2 mRNA expression level was positively correlated with plasma interleukin-6 level, indicating that transcriptional activation of Oat2 may occur in inflammatory state.