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基于网络药理学探讨葛根治疗缺血性脑卒中的效应机制

Exploring the Pharmacological Mechanism of Puerariae Radix on Cerebral Ischemic Stroke by a Network Pharmacology Approach
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摘要 目的运用网络药理学方法探究葛根治疗缺血性脑卒中(Cerebral ischemic stroke,CIS)的潜在效应机制。方法利用网络药理学分析平台(BATMAN-TCM)数据库收集葛根化学成分及其靶标基因。通过Gene Cards、Drug Bank、HPO、OMIM、TTD等数据库获取CIS疾病靶标基因。将成分靶标与疾病靶标上传至String数据库,构建中药成分靶标-疾病靶标蛋白互作网络,并计算网络特征值,筛选出关键靶标。借助DAVID分析平台对关键靶标进行基因本体(GO)分析和京都基因和基因组百科全书(KEGG)通路富集分析。结果共获取葛根成分18种,成分作用靶标467个,疾病靶标200个。葛根治疗CIS关键靶标180个,包括胰岛素、白细胞介素6、肿瘤坏死因子、Fos原癌基因、一氧化氮合酶3等基因,主要富集在神经活性配体-受体相互作用、胆碱能突触、谷氨酸能突触、钙信号通路、cAMP信号通路、RAP1信号通路、MAPK信号通路、PI3K-AKT信号通路、cGMP-PKG信号通路等多条信号通路。结论葛根治疗CIS的效应机制多与基因调控、抗炎、抗氧化应激和抗细胞凋亡相关。 Objective To explore the potential mechanism of Puerariae radix in the treatment of cerebral ischemicstroke using a network pharmacology approach. Methods Network pharmacology analysis platform(BATMAN-TCM)was used to collect the chemical constituents and target genes of Puerariae radix. Then, the Gene Cards, DrugBank,HPO,OMIM and TTD databases were used to obtain the target genes of cerebral ischemic stroke disease.Moreover,the component targets and disease targets were uploaded to String database to construct the interaction network among TCM component targets and disease targets, and we calculated the characteristic value of thisnetwork in order to screen out the key targets. Finally,Gene Ontology(GO) Analysis and Kyoto Encyclopedia ofGenes and Genomes(KEGG) were carried out with the aid of DAVID analysis platform. Results Base on theBATMAN-TCM,a total of 18 components of Puerariae radix were obtained,with 467 predicted targets and 200 disease targets. Based on network eigen values,180 key targets of Puerariae radix treating cerebral ischemic strokewere screened out, including INS, IL-6, TNF, Fos proto-oncogene, NOS3 and other genes. The biologicalpathways mainly involved in the neuroactive ligand receptor interaction, cholinergic synapse, glutaminergicsynapse, calcium signaling pathway, c AMP signaling pathway, RAP1 signaling pathway, MAPK signalingpathway, PI3 K-AKT signal pathway, c GMP-PKG signal pathway and other signal pathways. Conclusion Theresult of this study preliminarily reveals the effective mechanism of Puerariae radix in treating cerebral ischemicstroke,which is related to gene regulation,anti-inflammatory,anti-oxidative stress and anti-apoptosis.
作者 张昌林 倪小佳 古江勇 刘博 招远祺 蔡业峰 ZHANG Changlin;NI Xiaojia;GU Jiangyong;LIU Bo;ZHAO Yuanqi;CAI Yefeng(The Second Clinical School,Guangzhou University of Chinese Medicine,Guangzhou 510120 Guangdong,China;Encephalopathy Center of Guangdong Provincial Hospital of Chinese Medicine,Guangzhou 510120 Guangdong,China;Guangdong Provincial Academy of Chinese Medical Science & the Translational Medicine Research Teamof Cerebrovascular Disease (CVD) with TCM,Guangzhou 510120 Guangdong,China;The Basic Theory of Traditional Chinese Medicine Team,Guangdong Provincial Academy of Chinese Medical Science Guangzhou 510120 Guangdong,China;Chemical Research and Structural Optimization of Chinese Materia Medica Team,Guangdong Provincial Academy of Chinese Medical Science,Guangzhou 510120 Guangdong,China)
出处 《中药新药与临床药理》 CAS CSCD 北大核心 2019年第4期443-451,共9页 Traditional Chinese Drug Research & Clinical Pharmacology
基金 国家中医药管理局临床基地科研专项(JDZX2015207) 广州中医药大学高水平大学建设项目(A1-AFD018171Z11096,A1-AFD018171Z11097) 广东省中医院中医药科学技术研究专项(YN2015BZ05,YN2015MS03) 广州市科技计划项目(编号:201604020003) 广州中医药大学一流学科建设重点项目(A1-AFD018181A34).
关键词 葛根 缺血性脑卒中 网络药理学 靶点 作用机制 Puerariae radix cerebral ischemic stroke network pharmacology targets mechanism
作者简介 张昌林,男,广州中医药大学本硕连读生,研究方向:中药质控与中药药理学。Email:zhangchanglin1125@163.com;通信作者:倪小佳,女,博士,主治医师,研究方向:中西医结合神经病学的基础与临床研究。Email:grace1984325@126.com.
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