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炎症状态下许多重要的药物代谢酶表达及活性发生下调,药物代谢酶表达及活性的改变直接影响机体对药物的处置过程,导致药物不良反应的发生。大量研究表明,炎症反应中机体会释放大量的细胞因子,而其中某些炎性细胞因子参与下调药物代谢酶的表达及活性,其中细胞色素P450酶首当其冲。由于细胞因子对细胞色素P450酶的调节作用与炎症的发展程度以及疾病的治疗进程有关,临床上很难预测这种调节作用的结果。因此,弄清炎症情况下细胞因子对药物代谢酶的调节作用对分析和解释临床上发生的药物不良反应具有重要意义。本文综述了炎症状态下细胞因子对细胞色素P450酶的调控研究进展,探讨了其可能的作用机制以及临床意义。
Under the inflammatory state, many important drug metabolism enzymes are down-regulated in expression and activity. The changes in the expression and activity of drug-metabolizing enzymes have a direct impact on the body’s handling of the drug, leading to adverse drug reactions. A large number of studies have shown that the body will release a large number of inflammatory cytokines, and some of these inflammatory cytokines involved in the down-regulation of the expression and activity of drug-metabolizing enzymes, of which cytochrome P450 enzymes bear the brunt. As cytokines on the regulation of cytochrome P450 enzymes and the extent of the development of inflammation and disease progression, clinically difficult to predict the results of this regulatory role. Therefore, to clarify the regulatory role of cytokines on drug-metabolizing enzymes under inflammatory conditions is of great significance for the analysis and interpretation of adverse drug reactions occurring clinically. This review summarizes the progress of cytokines on the regulation of cytochrome P450 enzymes under inflammatory conditions and explores the possible mechanism of action and clinical significance.