目的 采用高效液相色谱-四极杆飞行时间串联质谱（HPLC-Q-TOF-MS/MS）挖掘益肾化湿颗粒的主要成分，并结合网络药理学探究益肾化湿颗粒治疗IgA肾病的作用靶点及机制。方法 采用质谱技术对益肾化湿颗粒主要成分进行准确定性，并运用TCMSP、ETCM、SymMAP数据库获得活性成分靶点；采用GeneCards、OMIM等数据库获得IgA肾病的疾病靶点，对药效疾病靶点进行基因本体（gene ontology，GO）富集分析及京都基因与基因组百科全书（Kyoto encyclopedia of genes and genomes，KEGG）通路分析，进一步运用Cytoscape_v3.8.2构建“活性成分-靶点-通路”网络；应用Atuodock软件对筛选靶点及主要活性成分进行分子对接，进行结合位点模拟验证。结果 共鉴定出益肾化湿颗粒主要成分68个，包括香豆素类、三萜类和黄酮类等化合物；共获得益肾化湿颗粒治疗IgA肾病活性成分43个，活性成分与疾病交集靶点74个，其中包括过氧化物酶体增殖物激活受体γ、皮质醇受体基因等；涉及通路包括肿瘤坏死因子信号通路、磷脂酰肌醇3激酶/蛋白激酶B信号通路、晚期糖基化产物-晚期糖基化终末产物受体信号通路等。分子对接结果显示，柴胡皂苷A、黄芪甲苷III、黄芪甲苷IV、泽泻醇A与IgA肾病的预测靶点有良好的结合活性。结论 益肾化湿颗粒能够通过抗炎、调节免疫、改善类固醇效应等治疗IgA肾病，具有多成分、多靶点、多途径的特点。

Objective To discover the main components of Yishen Huashi Granules (益肾化湿颗粒) by high performance liquid chromatography-quadrupole time-of-flight mass spectrometry (HPLC-Q-TOF-MS/MS), and explore the target and mechanism of Yishen Huashi Granules in treatment of IgA nephropathy by network pharmacology. Methods Mass spectrometry was used to accurately characterize the main components of Yishen Huashi Granules, and the active component targets were obtained by TCMSP, ETCM, and SymMAP databases; Disease targets of IgA nephropathy were obtained by GeneCards, OMIM and other databases, gene ontology (GO) enrichment analysis and Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis were performed on drug-effective disease targets, and "active ingredients-targets-pathway" network was further constructed by Cytoscape_v3.8.2; Atuodock software was used for molecular docking of screening target and main active ingredients, and binding site simulation verification was carried out. Results A total of 68 main components of Yishen Huashi Granules were identified, including coumarins, triterpenoids, and flavonoids. A total of 43 active components of Yishen Huashi Granules for treating IgA nephropathy were obtained, 74 targets were obtained at the intersection of active ingredients and diseases, including peroxisome proliferator-activated receptor γ, cortisol receptor genes, etc.; Tumor necrosis factor signaling pathway, phosphatidylinositol 3-kinase/protein kinase B signaling pathway, advanced glucose glycation products-advanced glycation end products receptor signaling pathway were involved. Molecular docking results showed that saikosaponin A, astragaloside III, astragaloside IV, alisol A had good binding activity with the predicted targets of IgA nephropathy. Conclusion Yishen Huashi Granules can treat IgA nephropathy through anti-inflammatory, immune regulation and steroid effects. It has the characteristics of multiple components, multiple targets and multiple pathways.

R285.5

益肾化湿颗粒临床应用研究和基础研究开放课题（康药合字2020336）