化浊解毒消痈方治疗溃疡性结肠炎机制的网络药理学研究  

Study on the Mechanism of Huazhuo Jiedu Xiaoyong Decoction in Treating Ulcerative Colitis Based on Network Pharmacology

作　　者：娄莹莹[1,2] 徐伟超 李佃贵[1] 霍永利 孙润雪[1] 李燕[3] 王思月 杨倩 Lou Yingying;Xu Weichao;Li Diangui;Huo Yongli;Sun Runxue;Li Yan;Wang Siyue;Yang Qian(Hebei Hospital of Chinese Medicine,Hebei,Shijiazhuang 050011,China)

机构地区：[1]河北省中医院,河北石家庄050011 [2]河北省中西医结合胃肠病研究重点实验室,河北石家庄050011 [3]河北中医药大学,河北石家庄050200

出　　处：《中国中医急症》2024年第1期1-6,56,共7页Journal of Emergency in Traditional Chinese Medicine

基　　金：国家自然科学基金青年基金项目(82104774);国家中医药管理局重大疑难疾病(溃疡性结肠炎)中西医临床协作试点项目(国中医药办医政发[2018]3号);河北省中医药管理局科研计划项目(2020021)。

摘　　要：目的基于网络药理学对化浊解毒消痈方治疗溃疡性结肠炎(UC)的分子机制进行研究。方法通过TCMSP数据库筛选化浊解毒消痈方中药的活性成分和作用靶点,然后采用GeneCards数据库筛选疾病作用相关基因,运用Cytoscape3.7.2软件构建“药物-成分-靶点”网络图,通过String数据库进行蛋白质-蛋白质相互作用网络,筛选化浊解毒消痈方治疗UC的核心靶点,再利用Cytoscape的ClueGO插件进行基因本体及KEGG信号通路富集分析,并通过动物实验进行验证。结果化浊解毒消痈方治疗UC共有81个活性成分和20个关键蛋白靶点,包括前列腺素过氧化物合酶2(PTGS2)、前列腺素过氧化物合酶1(PTGS1)、白细胞介素-6(IL-6)、白细胞介素-1β(IL-1β)、半胱氨酸蛋白酶9(CASP9)、过氧化物酶体增殖物激活受体γ(PPARG)、B细胞淋巴瘤2(BCL2)、细胞促凋亡蛋白(Bax)、半胱氨酸蛋白酶3(Caspase-3)等;GO分析和KEGG通路分析结果表明,化浊解毒消痈方治疗UC主要涉及膜微结构域、膜区、囊泡腔、核染色质等,生物学过程包括细胞对脂多糖的反应、凋亡信号通路的调节、氧化应激、细胞对抗生素的反应等,分子功能涉及细胞因子活性、核受体活性、受体配体活性、蛋白激酶调节剂活性、蛋白质丝氨酸/苏氨酸激酶活性等;主要富集于IL-17、PI3K-Akt、TNF信号通路等,主要通过调节炎症因子、免疫反应、细胞凋亡、抗病毒感染、抗癌等发挥作用。动物实验表明:模型组中小鼠血清IL-6、肿瘤坏死因子-α(TNF-α)升高,结肠组织中Bcl-2、Caspase-3蛋白表达升高;经过化浊解毒消痈方干预后,小鼠血清IL-6、TNF-α以及结肠组织Bcl-2、Caspase-3蛋白均表达下降。结论通过网络药理学研究化浊解毒消痈方治疗UC的潜在作用机制,揭示其多成分、多靶点、多途径的复杂作用过程,初步推测并验证了化浊解毒消痈方治疗UC的主要靶蛋白与通路,为临床应用提供Objective:To study the molecular mechanism of Huazhuo Jiedu Xiaoyong Decoction in the treatment of ulcerative colitis(UC)based on network pharmacology.Methods:TCMSP database was used to screen the active ingredients and target targets of the traditional Chinese medicine of Huazhuo Jiedu Xiaoyong Decoction.The disease targets were screened using the Gene Cards database.The protein-protein interaction network was carried out through the String database,and the core targets of the treatment of UC were screened,and then the ClueGO plug-in of Cytoscape was used for the enrichment analysis of gene ontology and KEGG signaling pathway,which was verified by animal experiments.Results:There were 81 active ingredients and 20 key protein targets of Huazhuo Jiedu Xiaoyong Decoction in the treatment of UC,including PTGS2,PTGS1,PPARG,Bax,Caspase-3,IL-6,IL-1β,CASP9,BCL2,etc.GO analysis and KEGG pathway analysis results showed that the treatment of UC by Huazhuo Jiedu Xiaoyong Decoction mainly involved membrane microdomains,membrane regions,vesicle cavities,nuclear chromatin,etc.The biological process included the response of cells to lipopolysaccharide,the regulation of apoptosis signaling pathway,and oxidation stress,cell response to antibiotics,etc.Molecular functions involved cytokine receptor binding,cytokine activity,nuclear receptor activity,receptor ligand activity,protein kinase modulator activity,protein serine/threonine kinase activity,etc.It was mainly enriched in IL-17,PI3K-Akt,and TNF signaling pathways.It was found that the treatment of UC by Huazhuo Jiedu Xiaoyong Decoction mainly played a role by regulating inflammatory factors,immune response,apoptosis,antiviral infection,and anticancer.The animal experiments showed that the serum IL-6 and TNF-αlevels of mice in the model group were increased,and the protein expressions of Bcl-2 and Caspase-3 in the colon tissue were increased.After the intervention of Huazhuo Jiedu Xiaoyong Decoction,the expression levels of IL-6 and TNF-αin the serum of mice and Bcl-2 and C

关 键 词：溃疡性结肠炎 化浊解毒消痈方 网络药理学 分子机制 

分 类 号：R574.62[医药卫生—消化系统]