糖皮质激素（glucocorticoid, GC）是由下丘脑-垂体-肾上腺皮质（hypothalamic-pituitary-adrenal cortex, HPA）轴调控释放的类固醇激素，1 型11β-羟基类固醇脱氢酶（11β-hydroxysteroid dehydrogenase-1, 11β-HSD1）作为体内GC的上游调节因子，在中枢神经系统退行性疾病致病过程中扮演着调控神经细胞内GC水平的重要作用。当HPA轴因机体应激或因某些病理条件导致能紊乱时，肾上腺皮质释放大量GC，无活性的皮质酮在细胞内被11β-HSD1可逆转化为皮质醇，并与糖皮质激素受体（glucocorticoid receptor, GR）结合发挥功能。GC水平异常升高并过度激活GR损伤海马神经元和神经突触的可塑性，进而造成认知障碍。本文结合国内外文献，从基因表达、空间分布等多方面阐述GC的上游调节因子11β-HSD 1对大脑中GC的调控作用及其对认知功能的影响，以期为脑退行性疾病的发病机制与早期干预提供新的思路。
Glucocorticoids (GC) are steroid hormones released by the hypothalamic-pituitary-adrenal cortex axis (HPA). 11β-hydroxysteroid dehydrogenase-1 (11β-HSD1), an upstream regulator of GC in vivo, plays a pivotal role in modulating GC levels in nerve cells during the pathogenesis of central nervous system degenerative diseases. Disruption of the HPA axis due to stress or pathological conditions leads to excessive release of GC from the adrenal cortex, where inactive corticosterone is reversibly converted into cortisol by 11β-HSD1 within the cell, binding with glucocorticoid receptor (GR) to exert its function. Abnormal elevation of GC levels and overactivation of GR impair hippocampal neuron and synapse plasticity, resulting in cognitive impairment. This article reviews the regulatory effect of 11β-HSD 1 on brain GC levels and its impact on cognitive function through gene expression and spatial distribution, aiming to provide new insights for understanding the pathogenesis and early intervention of brain degenerative diseases based on domestic and international literature.
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