目的 运用网络药理学方法及分子对接技术探讨黄芪干预腹膜纤维化的可能机制。方法 利用中药系统药理学数据库及分析平台(TCMSP)检索黄芪的主要化学成分及靶点,并补充文献报道相关药理作用的成分作为潜在活性成分。以"peritoneal fibrosis"为关键词分别在OMIM、Genecards获取目前已知的与腹膜纤维化相关的疾病靶点,后取两者的交集靶点;对交集基因通过STRING数据库与Cytoscape 3.7.2软件构建"药物-成分-靶点-疾病"网络及蛋白互作(PPI)网络并筛选核心网络。基于R软件使用Bioconductor生物信息软件对核心靶点进行GO及KEGG富集分析,最终采用AutoDock软件将主要有效成分与核心靶点进行分子对接,得出其结合能力。结果 筛选出20个黄芪活性成分及文献报道有相关药理作用4个, 457药物作用靶点,与674个腹膜纤维化病靶点取交集,得到86个共同靶点。GO功能富集分析提示黄芪拮抗腹膜纤维化主要参与了蛋白激酶B信号转导的调节、细胞对化学的应激反应、炎症反应的调节等通路; KEGG通路富集分析主要涉及调控肿瘤、磷脂酰肌醇-3-羟激酶-蛋白激酶B(PI3K-Akt)、晚期糖基化终末产物/晚期糖基化终末产物受体(AGE-RAGE)、人类巨细胞病毒感染、HIF-1信号通路等;分子对接结果显示关键靶点与活性成分具有较好的结合能力。结论 黄芪治疗腹膜纤维化的分子机制,可能与抑制炎症及氧化应激反应、调节多种信号通路等相关。

Objective To explore the possible mechanism of Astragali Radix intervention in peritoneal fibrosis by network pharmacology and molecular docking.Methods The main chemical components and targets of Astragalus membranaceus were searched using TCMSP, and the components with related pharmacological effects reported in literature were added as potential active ingredients. Using “peritoneal fibrosis ” as the key words, the current known peritoneal fibrosis -related disease targets were obtained from OMIM and Genecards database, and then the intersection of the two targets was selected. The “drug– component– target– disease” network and “protein-protein interaction (PPI)” network were constructed by STRING database and Cytoscape 3.7.2 software, and the core network was screened. GO and KEGG enrichment analysis of core targets was performed using Bioconductor bioinformation software based on R software. Finally, AutoDock software was used to carry out molecular docking between the main active ingredients and the core target, and its binding ability was obtained.Results 20 active components of Astragali Radix were screened out, and 4 of them reported related pharmacological effects, including 457 drug targets, and 86 common targets were obtained by intersection with 674 peritoneal fibrosis targets. GO enrichment analysis suggested that Astragali Radix antagonism against peritoneal fibrosis was mainly involved in the regulation of protein kinase B signal transduction, cell response to chemical stress, inflammatory response and other pathways. The enrichment analysis of KEGG pathway mainly involves the regulation of tumor, PI3KAkt, advanced glycation end-product/advanced glycation end-product receptor (AGE-RAGE), human cytomegalovirus infection, HIF1 signaling pathway, etc. The molecular docking results showed that the key target had good binding ability with the active ingredient.Conclusion This study elucidated the possible molecular mechanism of Astragali Radix in treatment of peritoneal fibrosis, which is related to the inhibition of inflammation and oxidative stress response, and the regulation of multiple signaling pathways.

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国家自然科学基金资助项目(81503533);江苏省“六大人才高峰”项目(WSN-021);江苏省自然科学基金面上项目(BK20211393)