基于代谢组学与网络药理学整合策略探讨交泰丸治疗抑郁症的作用机制  

Metabolomics combined with network pharmacology reveals mechanism of Jiaotai Pills in treating depression

作　　者：戴国梁[1] 陈泽瑀 王艳军 边欣芳 陈瑜洁 孙冰婷 王晓勇[1] 居文政[1] DAI Guo-liang;CHEN Ze-yu;WANG Yan-jun;BIAN Xin-fang;CHEN Yu-jie;SUN Bing-ting;WANG Xiao-yong;JU Wen-zheng(Affiliated Hospital of Nanjing University of Chinese Medicine,Nanjing 210029,China;School of Pharmacy,Xuzhou Medical University,Xuzhou 221004,China;Department of Pharmacy,Nanjing Hospital of Chinese Medicine,Nanjing 210022,China)

机构地区：[1]南京中医药大学附属医院,江苏南京210029 [2]徐州医科大学药学院,江苏徐州221004 [3]南京市中医院药学部,江苏南京210022

出　　处：《中国中药杂志》2025年第5期1340-1350,共11页China Journal of Chinese Materia Medica

基　　金：江苏省中医药科技发展计划面上项目(MS2021011);江苏省科技项目社会发展项目(BE2023790);江苏省医学重点实验室项目(ZDXYS202209);江苏省中医药管理局基地项目(JD2022SZ12)。

摘　　要：基于代谢组学与网络药理学整合策略探讨交泰丸治疗抑郁症的作用机制。运用UHPLC-Orbitrap Exploris 480对交泰丸的化学成分进行系统鉴定,基于在线数据库获取交泰丸成分作用靶点及抑郁症疾病靶点,利用STRING和Cytoscape 3.7.2构建交泰丸治疗抑郁症核心靶点的蛋白-蛋白互作网络及“化合物-靶点-通路”网络,采用DAVID数据库对核心靶点进行基因本体论(Gene Ontology,GO)功能和京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)通路富集分析。进一步构建慢性不可预知温和刺激(chronic unpredictable mild stress,CUMS)抑郁小鼠模型,给予不同剂量的交泰丸,观察小鼠行为学及海马组织病理形态变化。运用UHPLC-Orbitrap Exploris 120对抑郁模型小鼠血清代谢谱进行分析,筛选差异代谢物及相关代谢通路,并构建“代谢物-反应-酶-基因”网络进行代谢组学与网络药理学整合分析。结果显示,共鉴定出交泰丸相关成分34个,结合网络药理学分析,共获取交泰丸治疗抑郁症的核心靶点143个,上述靶点主要涉及鞘脂、神经营养因子、精氨酸和脯氨酸代谢等通路。动物实验结果表明,交泰丸可显著改善CUMS抑郁模型小鼠的抑郁样行为及海马组织病理形态。此外,交泰丸对CUMS抑郁模型小鼠血清中参与鞘脂代谢、卟啉代谢、精氨酸和脯氨酸代谢等代谢通路的32种代谢物具有显著回调作用,进一步整合分析显示半胱氨酸和蛋氨酸代谢、精氨酸和脯氨酸代谢以及卟啉代谢可能是交泰丸治疗抑郁症的关键通路。综上所述,该研究基于代谢组学与网络药理学整合策略初步阐明交泰丸抗抑郁的作用机制,可进一步为交泰丸抗抑郁的临床应用提供现代科学依据。This study aims to explore the mechanism of Jiaotai Pills in treating depression based on metabolomics and network pharmacology.The chemical constituents of Jiaotai Pills were identified by UHPLC-Orbitrap Exploris 480,and the targets of Jiaotai Pills and depression were retrieved from online databases.STRING and Cytoscape 3.7.2 were used to construct the protein-protein interaction network of core targets of Jiaotai Pills in treating depression and the"compound-target-pathway"network.DAVID was used for Gene Ontology(GO)function and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analyses of the core targets.The mouse model of depression was established with chronic unpredictable mild stress(CUMS)and treated with different doses of Jiaotai Pills.The behavioral changes and pathological changes in the hippocampus were observed.UHPLC-Orbitrap Exploris 120 was used for metabolic profiling of the serum,from which the differential metabolites and related metabolic pathways were screened.A"metabolite-reaction-enzyme-gene"network was constructed for the integrated analysis of metabolomics and network pharmacology.A total of 34 chemical components of Jiaotai Pills were identified,and 143 core targets of Jiaotai Pills in treating depression were predicted,which were mainly involved in the arginine and proline,sphingolipid,and neurotrophin metabolism signaling pathways.The results of animal experiments showed that Jiaotai Pills alleviated the depression behaviors and pathological changes in the hippocampus of the mouse model of CUMS-induced depression.In addition,Jiaotai Pills reversed the levels of 32 metabolites involved in various pathways such as arginine and proline metabolism,sphingolipid metabolism,and porphyrin metabolism in the serum of model mice.The integrated analysis showed that arginine and proline metabolism,cysteine and methionine metabolism,and porphyrin metabolism might be the key pathways in the treatment of depression with Jiaotai Pills.In conclusion,metabolomics combined with network phar

关 键 词：交泰丸 抑郁症 代谢组学 网络药理学 

分 类 号：R285[医药卫生—中药学]