目的 運用網(wǎng)絡(luò)藥理學方法及分子對接技術(shù)探討黃芪干預腹膜纖維化的可能機制。方法 利用中藥系統(tǒng)藥理學數(shù)據(jù)庫及分析平臺(TCMSP)檢索黃芪的主要化學成分及靶點,并補充文獻報道相關(guān)藥理作用的成分作為潛在活性成分。以"peritoneal fibrosis"為關(guān)鍵詞分別在OMIM、Genecards獲取目前已知的與腹膜纖維化相關(guān)的疾病靶點,后取兩者的交集靶點;對交集基因通過STRING數(shù)據(jù)庫與Cytoscape 3.7.2軟件構(gòu)建"藥物-成分-靶點-疾病"網(wǎng)絡(luò)及蛋白互作(PPI)網(wǎng)絡(luò)并篩選核心網(wǎng)絡(luò)?；赗軟件使用Bioconductor生物信息軟件對核心靶點進行GO及KEGG富集分析,最終采用AutoDock軟件將主要有效成分與核心靶點進行分子對接,得出其結(jié)合能力。結(jié)果 篩選出20個黃芪活性成分及文獻報道有相關(guān)藥理作用4個, 457藥物作用靶點,與674個腹膜纖維化病靶點取交集,得到86個共同靶點。GO功能富集分析提示黃芪拮抗腹膜纖維化主要參與了蛋白激酶B信號轉(zhuǎn)導的調(diào)節(jié)、細胞對化學的應激反應、炎癥反應的調(diào)節(jié)等通路; KEGG通路富集分析主要涉及調(diào)控腫瘤、磷脂酰肌醇-3-羥激酶-蛋白激酶B(PI3K-Akt)、晚期糖基化終末產(chǎn)物/晚期糖基化終末產(chǎn)物受體(AGE-RAGE)、人類巨細胞病毒感染、HIF-1信號通路等;分子對接結(jié)果顯示關(guān)鍵靶點與活性成分具有較好的結(jié)合能力。結(jié)論 黃芪治療腹膜纖維化的分子機制,可能與抑制炎癥及氧化應激反應、調(diào)節(jié)多種信號通路等相關(guān)。

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.

R285

國家自然科學基金資助項目(81503533);江蘇省“六大人才高峰”項目(WSN-021);江蘇省自然科學基金面上項目(BK20211393)