基于“成分-靶点-通路”的丹灯通脑胶囊治疗脑梗死作用机制研究  

Action Mechanism of Dandeng Tongnao Capsules in the Treatment of Cerebral Infarction Based on“Component-Target-Pathway”

作　　者：师莹莹 左莉华[1] 周霖[1] 刘芳芳[2] 李卓伦 贾清泉 薛鹏[3] 赵红宇[4] 孙志[1] 张晓坚[1] SHI Ying-ying;ZUO Li-hua;ZHOU Lin;LIU Fang-fang;LI Zhuo-lun;JIA Qing-quan;XUE Peng;ZHAO Hong-yu;SUN Zhi;ZHANG Xiao-jian(Department of Pharmacy,The First Affiliated Hospital of Zhengzhou University,Zhengzhou 450000,China;Department of Internal Medical Clinic,The First Affiliated Hospital of Zhengzhou University,Zhengzhou 450000,China;Department of Physical Examination,The First Affiliated Hospital of Zhengzhou University,Zhengzhou 450000,China;Department of Stomatology,The First Affiliated Hospital of Zhengzhou University,Zhengzhou 450000,China;Shenyang Pharmaceutical University,Shenyang 110000,China)

机构地区：[1]郑州大学第一附属医院药学部,郑州450000 [2]郑州大学第一附属医院内科门诊,郑州450000 [3]郑州大学第一附属医院体检科,郑州450000 [4]郑州大学第一附属医院口腔科,郑州450000 [5]沈阳药科大学,沈阳110000

出　　处：《中国药学杂志》2021年第3期195-203,共9页Chinese Pharmaceutical Journal

基　　金：国家自然科学基金项目资助(81703666)。

摘　　要：目的采用网络药理学方法探索丹灯通脑胶囊治疗脑梗死的"多成分-多靶点-多通路"的作用机制。方法基于网络数据库及文献挖掘获得丹灯通脑胶囊所含化学成分,以口服生物利用度(OB)≥30%和类药性(DL)≥0.18筛选潜在活性成分并预测其作用靶点,后进一步与脑梗死疾病相关靶点比对分析;进而构建成分靶点及疾病靶点的蛋白互作网络,整合筛选丹灯通脑胶囊治疗脑梗死的关键作用靶点,最后借助于DAVID数据库对关键靶点进行GO富集分析和KEGG通路注释分析。结果通过筛选得到丹参酮IIA、刺柄芒花、木犀草素等丹灯通脑胶囊的67个主要活性成分,这些成分可直接作用于BCL2、MMP9、TNF等25个靶点,而蛋白互作网络结果得到425个关键靶点,共涉及145个生物过程、49种细胞组分和57种分子功能及24条调控通路(P<0.05,FDR<0.05),显示丹灯通脑胶囊可能主要通过核转录mRNA分解代谢、靶向膜的蛋白翻译及基因表观遗传学的表达调控等生物过程,涉及RNA结合、蛋白结合及酶结合等分子功能发挥治疗脑梗死的作用,其作用机制可能与信号转导、细胞过程、遗传信息处理、生物体系统等多个相关调控通路有关。结论丹灯通脑胶囊治疗脑梗死的作用体现了中药多成分、多靶点、多途径的协同作用特点,为深入揭示丹灯通脑胶囊治疗脑梗死的作用机制提供了重要的科学依据。OBJECTIVE To investigate the"multi-components,multi-targets,and multi-pathways"mechanism of Dandeng Tongnao Capsules(DDTN)for the treatment of cerebral infarction(CI)using network pharmacology.METHODS The chemical components in DDTN were obtained from multiple databases and literature mining.The potential active components were screened by taking oral bioavailability(OB)≥30%and drug-likeness(DL)≥0.18 as indicators and the targets were predicted.The targets of CI were searched and compared with the predicted component targets.Then,the protein-protein interaction(PPI)networks of component targets and disease-related targets were constructed and integrated to screen the key targets of DDTN against CI.Finally,the GO enrichment analysis and KEGG pathway annotation analysis of key targets were conducted through the DAVID database.RESULTS Sixty-seven potential active components of DDTN were screened out,such as tanshinone IIA,formononetin,luteolin and et al,which could directly act on 25 targets for the treatment of CI,such as BCL2,MMP9,TNF and et al.And a total of 425 key targets were identified by PPI integration analysis,involving 145 biological process,49 cellular components,57 molecular functions and 24 regulatory pathways(P<0.05,FDR<0.05),which indicated that DDTN might have a role in treating CI by regulating some biological processes including nuclear-transcribed mRNA catabolic process nonsense-mediated decay,SRP-dependent cotranslational protein targeting to membrane and regulation of gene expression epigenetic,and some molecular function,such as RNA binding,protein binding,and enzyme binding.The mechanisms might be related to multiple regulatory pathways such as signal transduction,cellular processes,genetic information processing,and organismal systems.CONCLUSION The anti-cerebral infarction effect of DDTN shows the characteristics of traditional Chinese medicine,ie,multi-components,multi-targets,and multi-pathways.This research provides a scientific basis for further revealing the mechanism of the DDTN f

关 键 词：丹灯通脑胶囊 脑梗死 网络药理学 靶点 作用机制 

分 类 号：R965[医药卫生—药理学]