Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta, Canada.
J Pharm Pharm Sci. 2012;15(3):361-75. doi: 10.18433/j30300.
Inflammation, the host's response to infection and injury, is associated with altered expression of genes such as metabolizing enzymes, transporters, receptors and plasma proteins. The purpose of the present work was to characterize the effect of inflammation on selected molecular targets and transporters that affect drugs' action and disposition. We have used rats with adjuvant arthritis (AA), an animal model of chronic inflammation. The AA group received 0.2 ml of 50 mg ml-1 Mycobacterium butyricum suspended in squalene into the tail base. On day 12, the rats were euthanized and their organs (heart, liver, kidneys and intestine) excised. Expression of Cav1.2, β1-AR, β2-AR, α1A-AR, Nav1.2, Nav1.6, Kv1.5, Kv2.1, Kv3.1, oatp1a1, oatp1a5, oatp1b2, oatp2b1, oatp4a1, oat2, oat3, oct1, mdr1a, bsep, mrp1, mrp3, mrp6, IL-1α, IFN-γ, iNOS, MCP-1, IL-10, Cox-1 and Cox-2 were determined by real time polymerase chain reaction (RT-PCR). Inflammation resulted in a significant reduction of oct1, oatp4a1 and mrp1 gene expression in the liver and oatp2b1, mrp6 and bsep gene expression in the kidney. Oatp4a1 and mdr1a were found to be significantly upregulated in rat heart. In conclusion, inflammation alters the gene expression of some mediators and drug transporters that can influence the behavior of drugs in the body and contribute to therapeutic failure.
炎症是宿主对感染和损伤的反应，与代谢酶、转运体、受体和血浆蛋白等基因表达的改变有关。本研究的目的是描述炎症对影响药物作用和分布的某些分子靶标和转运体的影响。我们使用佐剂性关节炎（AA）大鼠作为慢性炎症的动物模型。AA 组大鼠尾基部注射 0.2ml 浓度为 50mg/ml 的丁酸分枝杆菌混悬液。第 12 天处死大鼠，取其心、肝、肾和肠等器官。应用实时聚合酶链反应（RT-PCR）检测 Cav1.2、β1-AR、β2-AR、α1A-AR、Nav1.2、Nav1.6、Kv1.5、Kv2.1、Kv3.1、oatp1a1、oatp1a5、oatp1b2、oatp2b1、oatp4a1、oat2、oat3、oct1、mdr1a、bsep、mrp1、mrp3、mrp6、IL-1α、IFN-γ、iNOS、MCP-1、IL-10、Cox-1 和 Cox-2 的表达。炎症导致肝脏中 oct1、oatp4a1 和 mrp1 基因表达显著下调，肾脏中 oatp2b1、mrp6 和 bsep 基因表达下调。大鼠心脏中 oatp4a1 和 mdr1a 显著上调。总之，炎症改变了一些介质和药物转运体的基因表达，这可能影响药物在体内的行为，并导致治疗失败。
