摘要
目的运用网络药理学、分子对接和体内实验方法分析斑蝥素致小鼠心肌损伤及黄芪多糖的保护作用机制。方法通过查阅文献筛选得到黄芪多糖的活性化学成分,利用TCMSP、Targetnet、SEA和SwissTargetPrediction等数据库筛选斑蝥素和黄芪多糖的作用靶点,利用GeneCards及OMIM数据库筛选心脏损伤的相关疾病靶点。将药物靶点和疾病靶点取交集,并利用Cytoscape3.10.2对交集靶点进行分析,筛选出核心靶点;运用David数据库实现GO和KEGG信号通路富集分析,并用AutoDock Vina软件进行分子对接验证。建立斑蝥素心脏损伤小鼠模型,并给予黄芪多糖低、中、高剂量进行干预,检测各组血清AST、LDH、cTnT和CK-MB水平,观察心肌组织的病理变化。结果共筛选出黄芪多糖的靶点272个,斑蝥素的靶点845个,心脏损伤疾病相关靶点2127个,交集靶点共56个。根据degree值由高到低筛选HSP90AA1、CASP3、SIRT1、GSK3B、ESR1、MMP9等为核心靶点;GO分析主要涉及对外源性刺激的反应、基因表达的负调控、蛋白丝氨酸激酶活性等;KEGG分析主要涉及AGE-RAGE信号通路、PI3K-Akt信号通路、VEGF信号通路、癌症通路等。分子对接显示核心靶点与黄芪多糖的活性成分具有较高的结合亲和力。动物实验表明,黄芪多糖可缓解斑蝥素引起的心脏损伤,降低血清AST、LDH、CK-MB和cTnT水平;改善心肌组织结构。结论黄芪多糖对斑蝥素诱导的小鼠心肌损伤具有明显的保护作用,其机制涉及HSP90AA1、CASP3、SIRT1、GSK3B、ESR1、MMP9等多靶点和AGE-RAGE信号通路、PI3K-Akt信号通路、VEGF信号通路等多途径,为黄芪多糖在心肌保护领域的应用提供了理论依据。
Objective To investigate the protective mechanism of astragalus polysaccharide(APS)against cantharidin-induced myocardial injury in mice using network pharmacology,molecular docking,and in vivo experiments.Methods The active chemical components of Astragalus membranaceus polysaccharides were screened by literature review.Target of cantharidin and Astragalus polysaccharides were screened by TCMSP,Targetnet,SEA and SwissTargetPrediction databases,and the disease targets related to heart injury were screened by GeneCards and OMIM databases.The drug targets and disease targets were intersected,and the intersecting targets were analyzed by Cytoscape 3.10.2 to screen out the core targets,and the David database was used to realize the enrichment analysis of GO and KEGG signaling pathways,and the molecular docking was verified by AutoDock Vina software.A cantharidin-induced heart injury mouse model was established,and low,medium and high doses of Astragalus polysaccharide were given for intervention,and the serum levels of AST,LDH,cTnT and CK-MB in each group were detected,and the pathological changes of myocardial tissue were observed.Results A total of 272 targets for astragalus polysaccharide,845 targets for cantharidin,and 2127 myocardial injury-related disease targets were identified,with 56 intersecting targets.Core targets,including HSP90AA1,CASP3,SIRT1,GSK3B,ESR1,and MMP9,were selected based on degree values.GO analysis highlighted responses to exogenous stimuli,negative regulation of gene expression,and protein serine kinase activity.KEGG analysis revealed involvement in AGE-RAGE,PI3K-Akt,VEGF,and cancer signaling pathways.Molecular docking demonstrated high binding affinity between core targets and astragalus polysaccharide components.Animal experiments showed that astragalus polysaccharide alleviated cantharidin-induced myocardial injury,reducing serum AST,LDH,CK-MB,and cTnT levels and improving myocardial tissue structure.Conclusions Astragalus polysaccharides have a significant protective effect on cantharidin-induced myocardial injury in mice,and its mechanism involves multiple targets such as HSP90AA1,CASP3,SIRT1,GSK3B,ESR1,MMP9,and multiple pathways such as AGE-RAGE signaling pathway,PI3K-Akt signaling pathway,VEGF signaling pathway,etc.,which provides a theoretical basis for the application of Astragalus polysaccharides in the field of myocardial protection.
作者
郭翠玲
潘越
梁国丽
杜明茗
马洁
唐文超
Guo Cuiling;Pan Yue;Liang Guoli;Du Mingming;Ma Jie;Tang Wenchao(School of Basic Medicine,Guizhou University of Traditional Chinese Medicine,Guiyang,Guizhou 550025,China;The Second Clinical Medical College,Guizhou University of Traditional Chinese Medicine,Guiyang,Guizhou 550025,China)
出处
《齐齐哈尔医学院学报》
2025年第24期2309-2318,共10页
Journal of Qiqihar Medical University
基金
贵州中医药大学大学生创新创业训练计划项目(贵中医大创合字〔2023〕18号)。
关键词
网络药理学
黄芪多糖
分子对接
斑蝥素
心肌损伤
Network pharmacology
Astragalus polysaccharides
Molecular docking
Cantharidin
Myocardial damage
