基于网络药理学和分子对接技术探讨肾炎康复片治疗IgA肾病的作用机制

Exploration of the mechanism of action of nephritis rehabilitation Tablets in the treatment of IgA nephropathy based on network pharmacology and molecular docking technology

目的应用网络药理学和分子对接技术,探讨肾炎康复片治疗IgA肾病的作用机制。方法通过数据库筛选肾炎康复片的主要活性成分,进行靶点预测。收集IgA肾病相关靶点,并与肾炎康复片活性成分靶点基因交集,选取共同靶点。构建蛋白质-蛋白质互作网络图和药物-活性成分-共同靶点网络图筛选出药物主要活性成分。通过MetaScape数据库进行基因本体(GO)分析和京都基因与基因百科全书(KEGG)通路富集分析并构建主要活性成分-靶点-信号通路网络图。选取关键成分和核心靶点,使用Pymol、MGLTools、AutoDock等软件做分子对接。结果肾炎康复片的活性化合物共有182个,涵盖310个作用靶点,IgA肾病相关疾病靶点有1190个。筛选出共同靶点119个,主要涉及肿瘤坏死因子(TNF)、磷脂酰肌醇3-激酶/蛋白激酶(PI3K/Akt)、白细胞介素17(IL-17)、细胞衰老、丝裂原活化蛋白激酶(MAPK)等信号通路。网络分析和分子对接结果提示肾炎康复片中关键成分豆甾醇、β-谷甾醇可能通过作用于核心靶点B细胞淋巴瘤-2基因(BCL2)、丝裂原活化蛋白激酶1(MAPK1)、胱天蛋白酶3(CASP3)发挥治疗IgA肾病的作用。结论肾炎康复片治疗IgA肾病具有多成分、多途径、多靶点的特点。

Objective To explore the mechanism of action of nephritis rehabilitation tablets in the treatment of IgA nephropathy using network pharmacology and molecular docking technology.Methods The main active ingredients of nephritis rehabilitation tablets were screened through a database and target prediction was performed.IgA nephropathy-related targets were collected and intersected with the active ingredient target genes of nephritis rehabilitation tablets to select common targets.The protein-protein interaction network diagrams and drug-active ingredient-common target network diagrams were constructed to screen the main active ingredients of the drug.The gene ontology(GO)analysis and Kyoto encyclopedia of genes and genomes(KEGG)pathway enrichment analysis were conducted using the MetaScape database,and a network diagram of the main active ingredient-target-signaling pathway was constructed.The key components and core targets were selected,and software such as Pymol,MGLTools,AutoDock,etc.was used for molecular docking.Results There were 182 active compounds in the nephritis rehabilitation tablets,covering 310 targets of action,and 1190 targets for IgA nephropathy-related diseases.119 common targets were screened,mainly involving signaling pathways such as tumor necrosis factor(TNF),phosphatidylinositol 3-kinase/protein kinase(PI3K/Akt),interleukin-17(IL-17),cell aging,and mitogen-activated protein kinase(MAPK).Network analysis and molecular docking results indicated that the key ingredients stigmasterol andβ-sitosterol in nephritis rehabilitation tablets may exert therapeutic effects on IgA nephropathy by targeting the core targets B-cell lymphoma 2 gene(BCL2),mitogen-activated protein kinase 1(MAPK1),and caspase 3(CASP3).Conclusion The treatment of IgA nephropathy with nephritis rehabilitation tablets has the characteristics of multiple components,pathways,and targets.