糖皮质激素非基因组效应的研究

在过去的几十年间，人们认为糖皮质激素（glucocorticoid，GC）仅仅是通过改变基因的表达来发挥其生理作用，这个过程需要几个小时来完成。然而，近年来越来越多的证据表明GC对激素分泌、神经元兴奋性、机体行为及细胞形态、糖类代谢等具备快速效应，这些过程往往在数秒钟或者分种内完成，这种作用机制被称为GC的非基因组作用机制。GC的非基因组作用主要可能通过两种不同的机制起作用：（1）通过细胞膜上或者细胞质内结构未知的糖皮质激素受体（glucocorticoid Recptor，GR）来发挥非基因组作用，即为特异性非基因组效应，（2）GC主要通过改变细胞膜理化作用来发挥效应。也称为非特异性非基因组效应（non-specific nongenomic effects，NSNE）。本文通过阐述近年来GC的非基因组的作用的最新研究进展并且讨论了这些非基因组作用临床治疗过程中的联系。对糖皮质激素基因组和非基因组作用机制的深入了解有助于指导我们在临床合理用药并减少其副作用。

Research on non-genomic glucocorticoid effects

For decades, it was widely considered that glucocorticoids （GCs） work solely through changes in gene expression to exert their physiological actions, a process that normally takes several hours to occur. However, recent evidence indicates that GCs might also act via non-genomic actions to exert multiple rapid effects such as hormone secretion, neuronal excitability, behavior, cell morphology, carbohydrate metabolism and other processes within seconds or minutes. It is assumed that rapid non-genomic glucocorticoid effects are mediated by two different mechanisms： （1） membrane-bound glucocorticoid receptor （mGR） and unknown cytosolic glucocorticoid receptor （cGR）-mediated non-genomic effects （specific nongenomic effects, SNE）; （2） physicochemical interactions with cellular membranes （non-specific non-genomic effects, NSNE）. This article summarized the latest progresses of non-genomic glucocorticoid effects and the relationship with clinical treatment. The right comprehends of non-genomic glucocorticoid effects guided us rational administration and the side-effect reducing.