中国临床药理学与治疗学2024，Vol.29Issue(6)：601-611,11.DOI:10.12092/j.issn.1009-2501.2024.06.001
基于网络药理学和实验验证探讨当归黄芪超滤物治疗放射性心肌纤维化的作用机制
Exploring the mechanism of Radix Angelica sinensis and Astragalus mongholicus extract therapy for radiationinduced myocardial fibrosis based on network pharmacology and experimental validation
摘要
Abstract
AIM:To explore the potential targets and mechanisms of Angelica sinensis and Astraga-lus membranaceus ultrafiltration(RAS-AM)in the treatment of radiation induced myocardial fibrosis(RIMF)through network pharmacology combined experimental validation.METHODS:Using the TC-MSP database TCM@TAIWAN The Taiwan Tradition-al Chinese Medicine Database and TCMID Tradition-al Chinese Medicine Database screen the compo-nents and targets of RAS-AM,and use the Swiss Target Prediction database for target prediction.Obtain RIMF disease targets from Gene Cards and OMIM databases,obtain intersection targets of dis-eases and drugs through Wayne's online tool,ob-tain protein interaction relationships(PPIs)through STRING database,and use Cytoscape 3.9.1 soft-ware to construct a visualized network topology di-agram of"drug component target disease".Con-duct GO and KEGG enrichment analysis on core tar-gets through the David database,and use the mi-crobiome platform for mapping.Experimental veri-fication:Sixty Wistar rats were randomly divided in-to a blank group,a model group,a positive drug group,a RAS-AM low-dose group,a RAS-AM medi-um dose group,and a RAS-AM high-dose group.A RIMF model was established using a 38Gy dose of radiation induction,and was administered orally for 4 weeks.The general condition of the rats was also observed.After blood and heart collection in rats,HE staining was used to observe the morpho-logical changes of myocardial tissue,and ELISA and Western blot methods were used to detect key tar-gets for network pharmacology prediction.RE-SULTS:Network pharmacology analysis revealed 34 active components and 705 targets of Angelica si-nensis and Astragalus membranaceus ultrafiltra-tion,with a total of 154 targets,with IL-6,VEGFA,MMP2,MMP9,and ACE as the top five core tar-gets;GO enrichment analysis screened a total of 153 entries,and KEGG enrichment had 25 path-ways.Experimental part:HE staining results showed that the degeneration and necrosis of myo-cardial cells improved in each medication group,the infiltration of inflammatory cells in the myocar-dial interstitium decreased,and the proliferation of fibrous connective tissue in the myocardial intersti-tium decreased.ELISA and Western blot results showed that compared with the normal group,the expression of IL-6,VEGFA,and MMP-9 in the mod-el group increased.Compared with the model groupthe expression of IL-6,VEGFA,and MMP-9 in each medication group decreased to varying de-grees,in a dose-dependent manner.CONCLUSION:RAS-AM may inhibit RIMF by downregulating core targets such as IL-6,VEGFA protein,MMP-9 pro-tein,and regulating inflammatory pathways,colla-gen degradation,and other processes.关键词
当归黄芪超滤物/放射性心肌纤维化/网络药理学/IL-6/VEGFA/MMP-9Key words
Angelica sinensis and Astragalus membranaceus ultrafiltration/radiationinduced myocardial fibrosis/network pharmacology/IL-6/VEGFA/MMP-9分类
医药卫生引用本文复制引用
李雯,蒋虎刚,王新强,李应东,刘凯,赵信科..基于网络药理学和实验验证探讨当归黄芪超滤物治疗放射性心肌纤维化的作用机制[J].中国临床药理学与治疗学,2024,29(6):601-611,11.基金项目
国家自然科学基金项目(82360926) （82360926）
中医药传承与创新"百千万"人才工程(岐黄工程)青年岐黄学者基金资助项目 （岐黄工程）
国家中医药管理局"李应东全国名中医传承工作室"建设项目(国中医药办人教函[2022]5号) （国中医药办人教函[2022]5号）
甘肃省科技重大专项计划(20ZD7FA002) （20ZD7FA002）
2021年度"双一流"科研重点项目(GSSYLXM-05-ZXYJH-5) （GSSYLXM-05-ZXYJH-5）
甘肃省中医药防治重大疾病科研课题项目(GZKZD-2018-02) （GZKZD-2018-02）
甘肃省教育科技创新项目教育揭榜挂帅基金资助项目(2021jyjbgs-03) （2021jyjbgs-03）
白银市科技计划项目(2022-2-50Y) （2022-2-50Y）
甘肃中医药大学第三附属医院院内课题(2022YK-11) （2022YK-11）
