目的 基于中医药治疗扩张型心肌病（dilated cardiomyopathy，DCM）的临床文献，分析其用药规律，并利用网络药理学及实验验证探讨清毒稳心方治疗DCM的作用机制。方法 在中国知网、万方和维普数据库中搜索与中医药治疗DCM相关的文献，经过筛选后建立中药处方数据库。采用SPSS Modeler及SPSS Statistics等软件工具，通过频数分析、关联规则及聚类分析等方法，总结中医药治疗DCM的用药规律，并得到核心方。借助中药系统药理学数据库与分析平台（traditional Chinese medicine systems pharmacology database and analysis platform，TCMSP）、Swiss Target Prediction和Swiss ADME数据库筛选药物活性成分及作用靶点，使用InteractiVenn获取相应药物与疾病靶点的交集，构建蛋白相互作用（protein-protein interaction，PPI）网络，并筛选核心靶点，构建“药物-有效成分-靶点”相互作用网络。采用Metascape数据库进行基因本体（gene ontology，GO）富集分析和京都基因与基因组百科全书（Kyoto encyclopedia of genes and genomes，KEGG）信号通路富集分析；并基于以上分析借助阿霉素诱导的小鼠DCM模型展开体内实验验证。结果 共纳入124篇文献，涵盖131个处方和166味中药，用药频次总计1 424次。其中高频药物（频次≥10次）32味，前5位的中药分别为黄芪、茯苓、丹参、甘草、桂枝；其中具有解毒作用的中药为益母草、升麻、黄连。在益气温阳、活血化瘀的基础上，优化配伍得到清毒稳心方，对清毒稳心方进行网络药理学分析，得到177个药物-疾病交集靶点以及10个药物核心活性成分，通过PPI网络分析，确定了7个核心靶点。KEGG通路分析主要富集在Apelin信号通路、钙信号通路等。实验验证发现，清毒稳心方可以明显改善心功能，治疗阿霉素诱导的DCM。结论 目前中医药治疗DCM主要以益气温阳、活血化瘀为主，基于毒邪理论及数据挖掘结果分析得到清毒稳心方。其主要活性成分可作用于酪氨酸蛋白激酶Src（proto-oncogene tyrosine-protein kinase Src，SRC）、丝裂原活化蛋白激酶1（mitogen-activated protein kinase 1，MAPK1）、MAPK3等潜在靶点；并且在Apelin和钙离子等信号通路发挥治疗作用。清毒稳心方可改善阿霉素诱导的DCM，其机制可能与调控SRC/蛋白激酶B（protein kinase B，AKT）/细胞外调节蛋白激酶（extracellular regulated kinase，ERK）信号通路有关。

Objective Based on clinical literature on traditional Chinese medicine (TCM) treatment of dilated cardiomyopathy (DCM), this study analyzed the medication rules and explored the mechanism of action of Qingdu Wenxin Formula (QD-WXF) in the treatment of DCM through network pharmacology and experimental validation. Methods Relevant literature related to the treatment of DCM with traditional Chinese medicine was retrieved from China national knowledge infrastructure (CNKI), Wanfang and VIP databases, establishing a database of traditional Chinese medicine prescriptions after screening. SPSS Modeler and SPSS Statistics were employed for frequency analysis, association rules and cluster analysis to summarize the medication rules and identify the core formula. Active ingredients and corresponding targets of QD-WXF were screened via traditional Chinese medicine systems pharmacology database and analysis platform (TCMSP), Swiss Target Prediction and Swiss ADME. InteractiVenn was used to obtain the intersection of the corresponding drugs and disease targets, construct protein-protein interaction (PPI) networks, and screen core targets to build a “drug-ingredient-target” interaction network. The Metascape database was used for gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) enrichment analyses. Based on the above analysis, an in-vivo model of doxorubicin-induced DCM in mice was used for experimental verification. Results A total of 124 articles were included, covering 131 prescriptions and 166 flavors of TCM, with a total of 1 424 drug use frequencies. A total of 32 herbs occurred ≥10 times. The top five TCMs were Huangqi (Astragali Radix), Fuling (Poria), Danshen (Salviae Miltiorrhizae Radix et Rhizoma), Gancao (Glycyrrhizae Radix et Rhizoma), and Guizhi (Cinnamomi Ramulus), among them, the TCM with detoxification effects were Yimucao (Leonuri Herba), Shengma (Cimicifugae Rhizoma), and Huanglian (Coptidis Rhizoma). On the basis of replenishing qi, warming yang, activating blood circulation and removing blood stasis, the QD-WXF was obtained by optimizing the compatibility. Network pharmacological analysis of QD-WXF resulted in 177 drug-disease intersection targets and ten core active ingredients of the drug, and seven core targets were identified through PPI network analysis. KEGG analysis showed significant enrichment in the Apelin signaling pathway, calcium signaling pathway, etc. In-vivo experiments confirmed that QD-WXF markedly improved cardiac function and treat DCM induced by doxorubicin. Conclusion Current TCM in treatment of DCM mainly focuses on replenishing qi, warming yang, and promoting blood circulation to resolve stasis. QD-WXF was obtained based on the analysis of the theory of toxic pathogen and data mining results. Its major active ingredients act on potential targets such as proto-oncogene tyrosine-protein kinase Src (SRC), mitogen-activated protein kinase 1 (MAPK1) and MAPK3 and other potential targets, and it plays a therapeutic role in signaling pathways such as Apelin and Calcium ion. QD-WXF can improve doxorubicin-induced DCM, and its mechanism may be related to the regulation of SRC/protein kinase B (AKT)/ extracellular regulated kinase (ERK) signaling pathway.

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国家重点研发计划项目（2022YFC3500105）；广东省方证研究重点实验室（2022B1212010012）；国家科技重大专项（2023ZD0502601）；中医药广东省实验室科技培植项目（HQL2024PZ045）；国家自然科学基金重点项目（82230262）；国家自然科学基金重点项目（U24A2074）