探讨中药致胆汁淤积型肝损伤的特点及调控机制  

Characteristics and Regulatory Mechanisms of Cholestatic Liver Injury Caused by Chinese Herbal Medicines

作　　者：杨云 张国壮 刘婷[1] 杨依霏[1] YANG Yun;ZHANG Guozhuang;LIU Ting;YANG Yifei(Institute of Chinese Materia Medica,China Academy of Chinese Medical Sciences,Beijing 100700,China)

机构地区：[1]中国中医科学院中药研究所,北京100700

出　　处：《中国实验方剂学杂志》2024年第23期64-71,共8页Chinese Journal of Experimental Traditional Medical Formulae

基　　金：北京市自然科学基金项目(7232301);中国中医科学院科技创新团队项目(CI2021B015);中国中医科学院科技创新工程项目(CI2021A04804);中央级公益性科研院所基本科研业务费专项(ZXKT22018,ZXKT21009,ZZ14-YQ-025)。

摘　　要：目的:基于数据挖掘、网络药理学及分子对接技术探讨中药导致胆汁淤积型肝损伤(CLI)的特点及其相关的调控路径。方法:利用中国知网、PubMed等数据库检索建库至2024年关于中药导致的相关文献,规范信息后汇总并进行聚类分析;运用中药系统药理数据分析平台(TCMSP)、中医药整合药理学研究平台(TCMIP),GeneCards、在线人类孟德尔遗传数据库(OMIM)、DisGeNET数据库检索核心药物靶点及相关靶点;利用韦恩图绘制核心药物与CLI的交集靶点;利用Cytoscape3.10.2构建交集靶点的蛋白相互作用(PPI)网络图;通过DAVID数据库对核心靶点进行基因本体(GO)和京都基因与基因组百科全书(KEGG)富集分析;最后用AutoDock Vina进行分子对接。结果:该研究共筛选出符合条件的文献849篇,统计出39味可导致胆汁淤积的中药及其单体成分64个。按2020年版《中华人民共和国药典》进行归类,其中报道频次由高到低依次为清热药、解表药、活血化瘀药、泻下药、化痰止咳平喘药、补益药、祛风湿药、温里药、利水渗湿药、理气药、止血药、攻毒杀虫止痒药、收涩药、化湿药、安神药。聚类分析发现清热药致CLI的研究报道数量最多,占比39.69%。其中,清热药中报道较多的是栀子(92篇,占比10.84%)、黄芩(76篇,占比8.95%)、苦参(69篇,占比6.95%)。网络毒理学研究可知被报道导致CLI的中药引起胆汁淤积的核心靶点主要包括肿瘤坏死因子(TNF)、过氧化物酶体增殖物激活受体α(PPARA)、法尼醇X受体(FXR)、谷丙转氨酶2抗体(GPT2)、超氧化歧化酶1(SOD1)、干扰素γ(IFN-γ)、白细胞介素-6(IL-6)、CD36、载脂蛋白A1(APOA1)、血管紧张素转化酶(ACE)、细胞色素P4503A4酶(CYP3A4)、蛋白激酶B1(Akt1)、APOB、白蛋白(ALB)、ATP结合盒转运蛋白B4(ABCB4)、SLC10A1、雌激素受体α(ESR1)、信号转导与转录激活因子1(STAT1)、肌动蛋白(ACTB)、内皮素1(EDN1)、ABCG2、Objective:To explore the characteristics and regulatory mechanisms of cholestatic liver injury(CLI)caused by traditional Chinese medicine based on data mining,network pharmacology,and molecular docking.Method:China National Knowledge Infrastructure and PubMed were searched for the relevant literature on CLI caused by traditional Chinese medicine from inception to 2024,and the information was standardized,summarized,and analyzed by cluster analysis.The Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP),Integrative Pharmacology-based Research Platform of Traditional Chinese Medicine(TCMIP),GeneCards,Online Mendelian Inheritance in Man(OMIM),and DisGeNET were used to retrieve the active ingredients and targets of core medicines.The Venn diagram was established to map the common targets shared by the core medicines and CLI.Cytoscape 3.10.2 was used to construct the protein-protein interaction(PPI)network of the common targets.DAVID was used for gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment of the core targets.Finally,molecular docking was performed by AutoDock Vina.Result:A total of 849 eligible articles were included in this study,from which 64 active ingredients of 39 herbal medicines that can cause cholestasis were counted and categorized according to the 2020 edition of the Pharmacopoeia of the People's Republic of China.The frequency of the medidicnes followed a descending order of heat-clearing medicines,exterior-releasing medicines,blood-activating and stasis-resolving medicines,purgative medicines,phlegm-resolving and coughand dyspnea-relieving medicines,tonics,wind-and dampness-expelling medicines,interior-warming medicines,urination-promoting and dampness-draining medicines,Qi movement-regulating medicines,hemostatics,toxin-removing,worm-killing,and itch-relieving medicines,astringent medicines,dampnesseliminating medicines,and tranquiling medicines.The cluster analysis revealed that the reports of CLI caused by heat-clearing medicines acco

关 键 词：中药 胆汁淤积 分子对接 网络毒理学 调控机制 

分 类 号：R284.2[医药卫生—中药学] R285[医药卫生—中医学] R289R287R22R2-031R33R24