目的 基于R语言数据挖掘、网络药理学及分子动力学模拟探讨国家专利中药复方治疗病毒性心肌炎（VMC）的用药规律及作用机制。方法 通过检索国家知识产权局专利数据库收集有关中药治疗VMC的专利复方，运用R语言进行频次、性味归经、关联规则和聚类分析，并获取核心药组。同时运用网络药理学筛选核心药组的活性成分及作用靶点，采用分子对接和分子动力学模拟加以验证。结果 共纳入国家专利中药复方299首，涉及中药679味。高频药物有黄芪、丹参等。其以性温、味甘常见，多归心、肺经。关联分析得到2阶关联中药有“丹参-黄芪”等，3阶有“丹参-五味子-黄芪”等；聚类分析得到人参-白术-远志-川芎-当归、甘草-地黄-茯苓-酸枣仁等5首新处方；筛选出核心药组为丹参-五味子-黄芪。网络药理学表明核心药组治疗VMC的主要活性成分有槲皮素、山柰酚、木犀草素、丹参酮ⅡA、7-O-甲基异微凸剑叶莎醇、异鼠李素、隐丹参酮等；核心靶点有蛋白激酶B抗体1（AKT1）、白细胞介素1β（IL1B）、肿瘤蛋白53（TP53）、IL6、肿瘤坏死因子（TNF）、半胱氨酸天冬氨酸蛋白酶3（CASP3）、基质金属蛋白酶9（MMP9）等；主要作用于TNF、IL^-17信号通路等。分子对接结果示，隐丹参酮与MMP9结合活性最优，分子动力学模拟进一步证实隐丹参酮与MMP9稳定且紧密结合。结论 国家专利中药复方治疗VMC多采用丹参-五味子-黄芪核心药组，其槲皮素、隐丹参酮等核心活性成分通过作用于AKT1、TP53、TNF、MMP9等关键靶点，调控TNF、IL^-17等信号通路，干预VMC“炎症-凋亡-纤维化”核心病理环节，从而发挥治疗作用。

Objective To investigate the prescription patterns and potential mechanisms of action of patented Chinese herbal formulas in the treatment of viral myocarditis (VMC) using R language-based data mining and a network pharmacology approach. Methods Through retrieving the patent database of the National Intellectual Property Administration, patent formulas for treating VMC with traditional Chinese medicine were collected. Using R language, frequency analysis, analysis of medicinal properties, flavors and meridian tropisms, association rule mining, and cluster analysis were conducted to identify the core herb combination. Furthermore, network pharmacology was employed to screen the active components and targets of the core combination, with validation through molecular docking and molecular dynamics simulations. Results A total of 299 national patented Chinese herbal compound prescriptions were included, involving 679 distinct herbs. High-frequency herbs included Astragalus membranaceus and Salvia miltiorrhiza. The herbal properties were predominantly warm, with sweet flavor being the most common, and the herbs primarily acted on the Heart and Lung meridians. Association analysis identified two-herb combinations such as “S. miltiorrhiza-A. membranaceus” and three-herb combinations like “S. miltiorrhiza-Schisandra chinensis-A. membranaceus”. Cluster analysis yielded five new prescriptions, including “Panax ginseng-Atractylodes macrocephala-Polygala tenuifolia-Ligusticum chuanxiong-Angelica sinensis” “Glycyrrhiza uralensis-Rehmannia glutinosa-Poria cocos-Ziziphus jujuba var. spinose”, and “Forsythia suspense-Lonicera japonicaIsatis indigotica”. The core herbal combination identified was S. miltiorrhiza-S. chinensis-A. membranaceus. Network pharmacology results indicated that the primary active components of this core combination for treating VMC included quercetin, kaempferol, luteolin, tanshinone IIA, 7-O-methylisomucronulatol, isorhamnetin, and cryptotanshinone. The core therapeutic targets were AKT1, IL1B, TP53, IL6, TNF, CASP3, and MMP9, primarily acting on the TNF signaling pathway and IL^-17 signaling pathway. Molecular docking results demonstrated that cryptotanshinone, an active component of the herbal combination, exhibited the strongest binding affinity with MMP9. Molecular dynamics simulations further confirmed the stable and tight binding between cryptotanshinone and MMP9. Conclusion The core herbal combination of S. miltiorrhiza-S. chinensis-A. membranaceus is commonly used in national patented Chinese herbal compounds for treating VMC. Its core active components, such as quercetin and cryptotanshinone, exert therapeutic effects by targeting key molecules including AKT1, TP53, TNF, and MMP9, regulating signaling pathways such as TNF and IL^-17, and intervening in the core pathological processes of VMC—inflammation, apoptosis, and fibrosis.

R285.5

国家自然科学基金面上项目（82574969）