Huisman A M, Jacobs J W G, Buttgereit F, Bijlsma J W J
Sint Franciscus Gasthuis, afd. Reumatologie, Kleiweg 500, 3045 PM Rotterdam.
Ned Tijdschr Geneeskd. 2006 Mar 4;150(9):476-80.
Two mechanisms of the genomic action ofglucocorticoids (GCs) can be distinguished: transrepression, yielding mainly an anti-inflammatory effect, and transactivation, resulting mainly in metabolic-endocrine side effects. Selective glucocorticoid receptor agonists (SEGRAs) cause selective transrepression, yielding the same anti-inflammatory effect as GCs, but with fewer side effects. NO is bound to several drugs to increase their effect; in nitrosteroids, NO is coupled to GC, resulting in a synergistic anti-inflammatory effect. Drug targeting can be achieved with GCs by incorporation of GC into polyethyleneglycol(PEG)-liposomes, resulting in very high concentrations ofGCs at the site of inflammation. Well-designed studies are needed to determine the place of SEGRAs, nitrosteroids and liposomal GCs in clinical practice.
糖皮质激素(GCs)的基因组作用机制可分为两种:反式抑制,主要产生抗炎作用;反式激活,主要导致代谢 - 内分泌副作用。选择性糖皮质激素受体激动剂(SEGRAs)引起选择性反式抑制,产生与GCs相同的抗炎作用,但副作用较少。一氧化氮(NO)与多种药物结合以增强其效果;在硝基甾体中,NO与GC偶联,产生协同抗炎作用。通过将GC掺入聚乙二醇(PEG)脂质体中,可实现GC的药物靶向作用,从而在炎症部位产生非常高浓度的GCs。需要精心设计的研究来确定SEGRAs、硝基甾体和脂质体GCs在临床实践中的地位。