基于网络药理学与分子对接技术探讨脊髓伤方治疗脊髓损伤的作用机制  

Exploration on mechanism of Jisuishang Formula in treating spinal cord injury based on network pharmacology and molecular docking technology

作　　者：莫怡[1] 卜若晨 唐福波[1] 秦百君 卜保献 麦威 钟远鸣[1] 卜献忠 MO Yi;BU Ruo-chen;TANG Fu-bo;QIN Bai-jun;BU Bao-xian;MAI Wei;ZHONG Yuan-ming;BU Xian-zhong(Department of Spinal Orthopedics,the First Affiliated Hospital of Guangxi University of Chinese Medicine,Nanning 530023,Guangxi,CHINA;Hainan Medical University,Haikou 570102,Hainan,CHINA;Department of Spinal Surgery,Luoyang Orthopedic-Traumatological Hospital of Henan Province(Henan Provincial Orthopedic Hospital),Luoyang 471002,Henan,CHINA;Department of Traditional Chinese Medicine,the Affiliated Cancer Hospital of Guangxi Medical University,Nanning 530021,Guangxi,CHINA)

机构地区：[1]广西中医药大学第一附属医院脊柱骨伤科,广西南宁530023 [2]海南医学院,海南海口570102 [3]河南省洛阳正骨医院(河南省骨科医院)脊柱外科,河南洛阳471002 [4]广西医科大学附属肿瘤医院中医科,广西南宁530021

出　　处：《海南医学》2023年第11期1521-1531,共11页Hainan Medical Journal

基　　金：国家自然科学基金委员会-地区科学基金项目(编号:81760874、82260942);广西科技计划项目-广西重点研发计划项目(编号:桂科AB20159018);广西中医药重点学科建设项目(编号:GZXK-Z-20-21);河南省中医药科学研究专项课题普通课题(编号:20-21ZY2083);洛阳市中医重点学科建设项目(编号:2022-2024);广西研究生教育创新计划资助项目(编号:YCBXJ2021009);广西壮族自治区中医药管理局计划课题(编号:GXZYA20220025)。

摘　　要：目的采用网络药理学与分子对接技术探讨脊髓伤方治疗脊髓损伤(SCI)的作用机制。方法通过中药系统药理学数据库与分析平台(TCMSP)与中国知网(CNKI)数据库筛选脊髓伤方的活性成分及其作用靶点,运用人类基因数据库(GeneCards)、在线人类孟德尔遗传数据库(OMIM)和治疗靶标数据库(TTD)等数据库挖掘SCI的疾病相关靶点;最终获取中药复方活性成分作用靶点与疾病相关靶点的交集靶点。运用Cytoscape 3.7.2软件与STRING数据库分别构建“活性成分-潜在作用靶点”和蛋白互作网络(PPI),筛选出潜在核心靶点;运用R软件和Metascape平台分别用于分析基因本体(GO)功能和京都基因与基因组百科全书(KEGG)途径的富集;对潜在靶点进行GO和KEGG富集分析。利用AutoDock Tools 1.5.6软件对关键化合物与核心靶点进行分子对接验证。结果共筛选获取138个活性成分及111个潜在作用靶点;获取到槲皮素、木犀草素、山柰酚、汉黄芩素、β-胡萝卜素等核心活性成分,白蛋白(ALB)、白介素6(IL-6)、丝氨酸/苏氨酸激酶1(AKT1)、管内皮生长因子A(VEGFA)、半胱氨酸天冬氨酸蛋白酶3(CASP3)、表皮生长因子受体(EGFR)、表皮生长因子(EGF)、转录因子AP-1(JUN)、白介素1B(IL1B)、转录3的信号换能器和激活子(STAT3)等核心靶点;共筛选获取179条信号通路,关键通路包括糖尿病并发症中晚期糖基化终产物及其受体(AGE-RAGE)信号通路、磷脂酰肌醇3-激酶-蛋白激酶B(PI3K-AKT)信号通路、缺氧诱导因子-1(HIF-1)信号通路、松弛素(RLX)信号通路、甲状腺激素(TH)信号通路、叉头盒O(FoxO)信号通路、阿佩林(AP)信号通路等。分子对接结果的最小结合能均<-5.0 kJ/mol,提示对接较良好。结论脊髓伤方可能是通过槲皮素、木犀草素、山柰酚、汉黄芩素、β-胡萝卜素等关键活性成分,调控ALB、IL-6、AKT1、VEGFA、CASP3等潜在核心靶点,调控AGE-RAGE、PI3K-AKT、HIF-1�Objective To investigate the mechanism of Jisuishang Formula(spinal cord injury prescription)in treating spinal cord injury(SCI)based on network pharmacology and molecular docking technology.Methods The ac-tive ingredients of spinal cord injury prescription and their targets were screened by Traditional Chinese Medicine Sys-tems Pharmacology Database and Analysis Platform(TCMSP)and CNKI databases,and the disease-related targets of SCI were screened by the Human Gene Database(GeneCard),online Mendelian Inheritance in Man(OMIM),and thera-peutic target database(TTD)databases to obtain the the intersection targets of the TCM compound active ingredients and the disease-related targets.Cytoscape 3.7.2 software and STRING database were used to construct the'active ingredi-ent-potential target'protein interaction network(PPI)and the potential core targets was screened.R software and Metascape platform were used to analyze gene ontology(GO)function and enrichment of Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway,respectively.GO and KEGG enrichment analysis was performed on potential targets.AutoDock Tools 1.5.6 software was used to verify the molecular docking between key compounds and core targets.Results A total of 138 active ingredients and 111 potential targets were screened.Core active compounds such as quer-cetin,luteolin,kaempferol,wogonin,β-carotene and core targets such as albumin(ALB),interleukin-6(IL-6),recep-tor-interacting protein serine-threonine kinases 1(AKT1),vascular endothelial growth factor A(VEGFA),Caspase-3(CASP3),epidermal growth factor receptor(EGFR),epidermal growth factor(EGF),transcription factor AP-1(JUN),in-terleukin-1B(IL1B),and signal transducer and activator of transcription 3(STAT3)were obtained.A total of 179 signal-ing pathways were screened,including advanced glycation end product-receptor for AGE signaling pathway in diabetic complications(AGE-RAGE)signaling pathway,phosphoinositide 3-kinase-Protein kinase B(PI3K-AKT)signaling pathway,hypoxia-inducible factor-1(HIF-1)signaling p

关 键 词：脊髓伤方 脊髓损伤 网络药理学 木犀草素 槲皮素 丝氨酸/苏氨酸激酶1 分子对接 

分 类 号：R744[医药卫生—神经病学与精神病学]