四氢孕酮:抑郁和焦虑障碍治疗的潜在新靶点  被引量:2

Allopregnanolone as a New Therapeutic Target for Depression and Anxiety

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作  者:蒋湘云[1,2] 尚超[3] 李雷[1,2] 孙树峥 李云峰[3] 王恒林[2] 

机构地区:[1]河北北方学院研究生部 [2]北京解放军第309医院麻醉科 [3]军事医学科学院毒物药物研究所

出  处:《神经药理学报》2016年第2期26-30,共5页Acta Neuropharmacologica

基  金:国家自然科学基金项目(No.81173036;No.81001635;No.30973516);全军医学科技十二五面上项目(No.CWS12J084)

摘  要:四氢孕酮(allopregnanolone)是18 k Da转位蛋白(the translocator protein,TSPO)介导胆固醇从线粒体外膜转运至内膜,继而经过一系列酶促反应后生成的神经类固醇。近年来的研究表明,以四氢孕酮为代表的神经类固醇含量下降参与了焦虑和抑郁等多种精神障碍性疾病的发生发展过程,且外源性给予四氢孕酮能够显著改善焦虑抑郁症状。四氢孕酮抗焦虑与抗抑郁的机制目前认为主要与四氢孕酮正向调节γ-氨基丁酸A(γ-aminobutyric acid A,GABAA)受体有关。此外,四氢孕酮还能调节下丘脑-垂体-肾上腺(hypothalamushypophysis-adrenal,HPA)轴的兴奋性,促进神经再生,产生神经保护作用。该综述将就四氢孕酮的产生,在焦虑及抑郁症中的作用及其可能机制进行阐述。Allopregnanolone-the neurosteroid is synthetized from cholesterol via TSPO mediated transfer from outer mitochondrial membrane to inner mitochondrial membrane. Recent study showed reduced level of neurosteroids represented by allopregnanolone were involved in the occurrence and development process of many mental disorders including anxiety and depression. Moreover, exogenous allopregnanolone treatment can significantly improve the anxious and depressive symptoms. The mechanisims underlying the antidepressant and anxiolytic effects of allopregnanolone were considered mainly to be associated with its positive activation on GABAA receptor. In addition,allopregnanolone played an important role in regulating functions of HPA axis as well as stimulating neurogenesis. This review described the production process of allopregnanalone,its role in anxiety and depression and its possible mechanisms of treatment effects.

关 键 词:四氢孕酮 焦虑 抑郁 Γ-氨基丁酸A受体 下丘脑-垂体-肾上腺轴 神经再生 

分 类 号:R964[医药卫生—药理学]

 

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