基于单细胞测序探讨金丝桃素抗抑郁的作用机制  

Exploring mechanism of action of hypericin in antidepressant effects based on single-cell sequencing

作　　者：倪慧心 刘海鑫 周炳灿 陈明恒 林萍燕 高正涛 林新培 林瑶[1] 吴方真 许茜[1] NI Hui-xin;LIU Hai-xin;ZHOU Bing-can;CHEN Ming-heng;LIN Ping-yan;GAO Zheng-tao;LIN Xin-pei;LIN Yao;WU Fang-zhen;XU Qian(College of Integrative Medicine,Academy of Intergrative Medicine,Fujian University of Traditional Chinese Medicine,Fuzhou 3501222,China;Dept of Rheumatology and Endocrinology,the Second Affiliated Hospital of Fujian Traditional Chinese Medical University,Fuzhou 350001,China)

机构地区：[1]福建中医药大学,中西医结合学院,中西医结合研究院,福建福州350122 [2]福建省第二人民医院风湿内分泌科,福建福州350001

出　　处：《中国药理学通报》2025年第5期837-843,共7页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No 81904263);福建省自然科学基金资助项目(No 2024J01745,2024J01123);福建中医药大学中医健康管理学联合省级临床重点专科建设项目(老年病科)(No XJG2023018);福建中医药大学校管课题青年项目(No X2023010)。

摘　　要：目的运用单细胞测序技术探究金丝桃素抗抑郁的作用机制。方法将C57BL/6小鼠随机分为正常组、抑郁症模型组、金丝桃素干预组。慢性不可预知温和应激(chronic unpredictable mild stress,CUMS)造模与药物干预持续28 d后,通过行为学实验评估抑郁症状,并采集海马组织进行单细胞测序。筛选重点细胞亚群以及各组的差异基因,进行PPI网络、GO和KEGG富集分析。结果行为学实验显示,CUMS造模成功诱导小鼠抑郁症状,金丝桃素改善抑郁行为。在抑郁症模型组中,脑血管周围巨噬细胞(brain perivascular macrophages,PVM)比例增加,金丝桃素干预后该比例有所下降,且接近正常组;PVM亚群的top20共同差异基因为Saa3、Hbb-bs、Ccl24;PPI网络分析显示核心靶点为Ccl2、Dhx9、C3、Msr1、Cxcl2、Cx3cr1;KEGG富集分析涉及趋化因子、吞噬体、肌醇磷酸代谢等通路。结论金丝桃素抗抑郁的作用机制可能与PVM调节Ccl24及其相关的趋化因子信号通路有关。Aim To investigate the antidepressant mechanism of hyperforin via the utilization of single-cell sequencing technology.Methods C57BL/6 mice were randomly divided into the control group,depression model group,and hyperforin intervention group.The chronic unpredictable mild stress(CUMS)model was induced and drug interventions were administered for 28 d.Behavioral experiments were conducted to assess depressive symptoms,and hippocampal tissue was collected for single-cell RNA sequencing.Key cell populations and differentially expressed genes across groups were identified,followed by PPI network,GO,and KEGG enrichment analysis.Results Behavioral experiments indicated that CUMS successfully induced depressive symptoms in mice,while hyperforin improved depressive behavior.In the depression model group,the proportion of brain perivascular macrophages(PVM)increased,and this proportion decreased after hyperforin intervention,approaching the level seen in the control group.The top 20 common differentially expressed genes in the PVM subpopulation were Saa3,Hbb-bs and Ccl24.PPI network analysis identified core targets,including Ccl2,Dhx9,C3,Msr1,Cxcl2 and Cx3cr1.KEGG enrichment analysis revealed pathways related to chemokines,phagosome formation,and inositol phosphate metabolism.Conclusion The antidepressant mechanism of hyperforin may be related to the regulation of Ccl24 and its related chemokine signaling pathway by PVM.

关 键 词：抑郁症 单细胞测序 金丝桃素 脑血管周围巨噬细胞 Ccl24 趋化因子信号通路 

分 类 号：R-332[医药卫生] R284.1R329.24R394.2R749.41