苦味受体激动剂在抑郁症中的研究进展  

Research progress on bitter taste receptor agonists in depression

作　　者：葛海龙 肖玲[1] 谢银平 司璐佳 孙丽敏 元国豪 李晨[1] 王高华[1] Ge Hailong;Xiao Ling;Xie Yinping;Si Lujia;Sun Limin;Yuan Guohao;Li Chen;Wang Gaohua(Departmen of Psychiatry,Renmin Hospital of Wuhan University,Wuhan 430060,China;The Institute of Neuropsychiatric Research of Hubei Province,Wuhan 430060,China)

机构地区：[1]武汉大学人民医院精神科,武汉430060 [2]湖北省神经精神病研究所,武汉430060

出　　处：《中华精神科杂志》2024年第4期251-256,共6页Chinese Journal of Psychiatry

基　　金：国家自然科学基金(81871072,82071523);武汉大学腾飞计划(TFLC2018001);湖北省重点研发项目(2020BCA064)。

摘　　要：抑郁症严重影响全球超过3亿人的生命健康及生活质量,鉴于抑郁症发病机制不明,且抗抑郁药物起效缓慢、疗效不佳,现亟需开辟新思路研究其发病机制及寻找新的治疗靶点。临床及临床前研究表明,大量苦味受体(taste receptor type 2 members,Tas2Rs)激动剂如表没食子儿茶素没食子酸酯(Epigallocatechin gallate,EGCG)、白藜芦醇、咖啡因、啤酒花与黄连素等均可显著缓解抑郁患者症状,并干预各类抑郁动物模型抑郁样行为,提示Tas2Rs激动剂参与调节抑郁症的发病过程,然而其抗抑郁作用的具体机制鲜有报道。最近研究显示,Tas2Rs激动剂密切参与了神经递质的调节、炎症信号的传导、脑肠信号交流及血脑脊液屏障物质交换等过程。因此,本文试图从神经递质、炎症、脑肠轴、血脑脊液屏障及其他5个方面出发,综述Tas2Rs激动剂与抑郁症可能相关的致病机制及治疗靶点,为抑郁症病理机制研究及新药研发提供新的思路。Depression is a common debilitating disorder affecting over 300 million individuals worldwide,emphasizing the pressing need to develop novel treatment targets for this disorder.Nevertheless,the pathophysiology of this disorder remains incompletely elucidated,and the currently available antidepressant treatments are suboptimal in terms of their efficacy and delayed onset of action.Thus,identifying and exploring new therapeutic avenues is of paramount importance.Recent clinical and preclinical studies have demonstrated that numerous bitter taste receptor type 2 members(Tas2Rs)agonists,including epigallocatechin gallate(EGCG),resveratrol,caffeine,humulones,and berberine,can significantly alleviate depressive symptoms in both human patients and animal models of depression.However,the precise mechanisms underlying the antidepressant effects of Tas2Rs agonists remain largely unknown.Intriguingly,a growing body of evidence suggests that Tas2Rs agonists may modulate various signaling pathways and systems including neurotransmission,inflammation,brain-gut axis,and the blood-cerebrospinal fluid barrier,all of which are believed to be implicated in the pathophysiology of depression.Therefore,this review aims to provide a comprehensive overview of the potential mechanisms of Tas2Rs agonists in depression,It synthesizes current evidence regarding its involvement in neurotransmission,inflammation,brain-gut communication,blood-cerebrospinal fluid barrier function,and other relevant pathways.This review will not only provide a valuable foundation for future research on the therapeutic potential of Tas2Rs agonists for depressive disorders but also offer new insights into the understanding of the pathophysiology of depression and the development of novel treatment strategies for this disorder.

关 键 词：抑郁症 苦味受体激动剂 表没食子儿茶素没食子酸酯 白藜芦醇 咖啡因 啤酒花 黄连素 

分 类 号：R749.4[医药卫生—神经病学与精神病学]