麝香通心滴丸改善心肌缺血再灌注损伤的网络药理学分析及动物实验验证研究  

Molecular Mechanism Study of Shexiang Tongxin Dripping Pills in Improving Myocardial Ischemia-reperfusion Injury:a Network Pharmacology Analysis and Animal Experiment Validation

作　　者：牛超峰 张立晶[1] 刘碧绒 肖狄 刘用 张超 张沛宇 李蒙 NIU Chaofeng;ZHANG Lijing;LIU Birong;XIAO Di;LIU Yong;ZHANG Chao;ZHANG Peiyu;LI Meng(Dongzhimen Hospital,Beijing University of Chinese Medicine,Beijing 100700,China;Dongfang Hospital,Beijing University of Chinese Medicine,Beijing 100078,China)

机构地区：[1]北京中医药大学东直门医院,北京100700 [2]北京中医药大学东方医院,北京100078

出　　处：《中西医结合心脑血管病杂志》2025年第4期513-524,共12页Chinese Journal of Integrative Medicine on Cardio-Cerebrovascular Disease

基　　金：北京中医药大学重点攻关项目(No.2020-JYB-ZDGG-116);吴阶平医学基金会资助项目(No.320.6750.2022-25-12)。

摘　　要：目的:利用网络药理学和动物实验验证的方法探索麝香通心滴丸治疗心肌缺血再灌注损伤的分子机制。方法:通过检索中药系统药理学分析平台(TCMSP)和在线生物信息学分析工具(BATMAN TCM)数据库,获取麝香通心滴丸的活性成分并筛选出相关靶点,同时收集心肌缺血再灌注损伤相关靶点,将两者取交集。构建蛋白质相互作用网络,并进行基因本体论(GO)功能富集和京都基因与基因组百科全书(KEGG)通路富集分析,进一步构建活性化合物-靶点网络和中药-靶点-通路网络图。最后,进行动物实验验证潜在机制。结果:麝香通心滴丸含有122种化学成分,485个相关靶点,其中165个与心肌缺血再灌注损伤相关。蛋白质-蛋白质相互作用(PPI)网络分析表明蛋白激酶B1(AKT1)、肿瘤坏死因子(TNF)、TP53、信号转导与转录激活因子3(STAT3)、JUN、白细胞介素(IL)6、IL1B等靶点为关键靶点。KEGG富集分析显示麝香通心滴丸通过多条信号通路发挥作用。动物实验结果与网药预测相符,基因组测序和蛋白质检测结果显示麝香通心滴丸可能通过调节缺氧诱导因子-1α(HIF-1α)和血管内皮生长因子(VEGF)来治疗心肌缺血再灌注损伤。结论:本研究全面展示了麝香通心滴丸治疗心肌缺血再灌注损伤的有效成分、分子机制和潜在靶点。Objective:To explore the molecular mechanisms underlying the therapeutic effects of Shenxiang Tongxin Dripping Pills on myocardial ischemia-reperfusion injury(MIRI)using a combination of network pharmacology analysis and animal experiments.Methods:The active ingredients of Shexiang Tongxin Dripping Pills were retrieved from the traditional Chinese medicine systems pharmacology database and analysis platform(TCMSP)and BATMAN TCM databases,and their corresponding target proteins were screened.Additionally,MIRI-related target proteins were collected,and the intersection of these two sets of targets was obtained.Protein-protein interaction(PPI)networks were constructed,and gene ontology(GO)and Kyoto Encyclopaedia of Genes and Genomes(KEGG)pathway enrichment analyses were performed.Furthermore,compound-target and herb-target-pathway networks were visualized.Animal experiments were conducted to validate the potential mechanisms.Results:The results showed that Shexiang Tongxin Dripping Pills contained 122 chemical components and 485 related target proteins,of which 165 were associated with MIRI.PPI network analysis revealed key targets such as protein kinase B1(AKT1),tumor necrosis factor(TNF),TP53,signal transducer and activator of transcription 3(STAT3),JUN,interleukin(IL)6,and IL1B.KEGG pathway enrichment analysis indicated there were imultiple signaling pathways in the therapeutic effects of Shexiang Tongxin Dripping Pills.The results of the animal experiments were consistent with the predictions of the network pharmacology analysis.The results of genome sequencing and protein detection showed that Shexiang Tongxin Dropping Pills may treat MIRI by regulating hypoxia-inducible factor(HIF)-1αand vascular endothelial growth factor(VEGF).Conclusion:This study comprehensively elucidated the effective components,molecular mechanisms,and potential targets of Shexiang Tongxin Dripping Pills for the treatment of MIRI.

关 键 词：心肌缺血再灌注损伤 麝香通心滴丸 网络药理学 作用机制 

分 类 号：R285.5[医药卫生—中药学]