摘要
目的:基于超高效液相色谱-四级杆飞行时间质谱(UPLC-Q-TOF-MS/MS)技术和网络药理学探讨柔肝方治疗肝纤维化的作用机制。方法:将8只C57BL/J小鼠随机分成空白血清组和柔肝方含药血清组,每组4只。利用UPLC-Q-TOF-MS/MS技术结合Xcalibur软件分析空白血清和柔肝方含药血清数据,结合二级谱图鉴定柔肝方的入血成分。通过Swiss Target Prediction数据库和中药系统药理学数据库与分析平台(Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform,TCMSP)检索柔肝方入血成分的靶点。利用GeneCards、OMIM、PharmGKB、DrugBank Online和Therapeutic Target Database数据库检索肝纤维化的靶点。采用Cytoscape软件构建“疾病-化合物-靶点”网络,并筛选柔肝方抗肝纤维化的关键成分。借助STRING数据库构建蛋白质-蛋白质相互作用(protein-protein interaction,PPI)网络,通过拓扑分析筛选柔肝方抗肝纤维化的核心靶点。采用DAVID数据库进行基因本体(gene ontology,GO)和京都基因与基因组百科全书(kyoto encyclopedia of genes and genomes,KEGG)分析。结果:柔肝方入血成分主要包括氧化槐果碱、槐果碱、高黄芩素、新补骨脂异黄酮等。通过检索获取柔肝方入血成分相关靶点303个,肝纤维化相关靶点6 331个,两者的交集靶点250个。柔肝方抗肝纤维化的关键成分包括槲皮素、芹菜素、山柰酚、芒柄花黄素等。柔肝方抗肝纤维化的核心靶点包括原癌基因酪氨酸蛋白激酶Src(SRC)、信号转导和转录激活因子3(signal transducer and activator of transcription 3,STAT3)、丝裂原活化蛋白激酶1(mitogen-activated protein kinase 1,MAPK1)、丝氨酸/苏氨酸蛋白激酶(protein kinase B,PKB,又称AKT1)等。GO分析主要涉及细胞因子介导的信号通路、凋亡过程的负调控、炎症反应、蛋白激酶活性等。KEGG分析主要涉及PI3K-Akt信号通路、MAPK信号通路、白细胞介素(interleukin,IL)-17信号�
Objective:To study the therapeutic mechanism of Liver-Softening Formula in treating liver fibrosis based on ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS/MS) technology and network pharmacology.Methods:A total of 80 C57BL/J mice were randomly divided into the blank serum group and the group of drug-containing serum from Liver-Softening Formula,with 4 mice in each group.The data of blank serum and drug-containing serum from Liver-Softening Formula were analyzed by UPLC-Q-TOF-MS/MS technology combined with Xcalibur software,and the blood-entering components of Liver-Softening Formula were identified combined with secondary mass spectrum.By using Swiss Target Prediction database and Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP),the targets of blood-entering components in Liver-Softening Formula were searched.The targets of liver fibrosis were searched using GeneCards,OMIM,PharmGKB,DrugBank Online,and Therapeutic Target Database databases.Using Cytoscape software,a "disease-compound-target" network was constructed,and the key components of Liver-Softening Formula in its anti-liver fibrosis effect were screened.The protein-protein interaction(PPI) network was constructed with the help of STRING database,and the core targets of Liver-Softening Formula in its anti-liver fibrosis were screened by topological analysis.Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) were analyzed using the DAVID database.Results:The main components of Ruogan prescription into blood included Oxysophocarpine,Sophocarpine,Scutellarein,Neobavaisoflavone,etc.A total of 303 related targets and 6 331 related targets of liver fibrosis,and 250 intersection targets of the two were obtained.The key components of Liver-Softening Formula in its anti-liver fibrosis effect include Quercetin,Apigenin,Kaempferol,Formononetin and so on.The core targets of Liver-Softening Formula in its anti-liver fibrosis effect included proto-oncogene tyro
作者
游丽萍
林佳成
李文轩
孔晓妮
高月求
王灵台
孙学华
YOU Liping;LIN Jiacheng;LI Wenxuan;KONG Xiaoni;GAO Yueqiu;WANG Lingtai;SUN Xuehua(Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine,Shanghai,China,200021)
出处
《河南中医》
2024年第7期1070-1078,共9页
Henan Traditional Chinese Medicine
基金
国家自然科学基金项目(82074336,82374251)
2023年上海市卫生健康领军人才计划项目(2022LJ013)
浦东新区卫生健康委员会学科建设项目(中医肝病临床专科重点学科)(PWZxq2022-04)
2022年国家中医药管理局高水平中医药重点学科建设项目(中医肝胆病学)(zyyzdxk-2023060)。
