基于代谢组学、网络药理学及分子对接技术探究芪蓟肾康汤治疗紫癜性肾炎的作用机制

Exploration on the mechanism of Qiji Shenkang Decoction in the treatment of purpuric nephritis based on metabolomics, network pharmacology and molecular docking technology

目的:运用代谢组学、网络药理学及分子对接等技术,探究芪蓟肾康汤治疗紫癜性肾炎(HSPN)的作用机制。方法:利用SIMCA及MetaboAnalyst分析患儿尿液代谢组信息,评价芪蓟肾康汤的治疗效益、分析HSPN潜在发病机制及生物标志物;依靠网络药理学探究芪蓟肾康汤的治疗机制;使用AutoDock验证芪蓟肾康汤核心化合物的治疗机制。结果:研究发现HSPN的发病机制与人体精氨酸代谢异常密切相关。网络药理学结果表明,槲皮素、木犀草素、山柰酚、芒柄花素及异鼠李素是芪蓟肾康汤发挥药效的重要成分;PTGS2、PTGS1、F2、ESR1及PRSS1是芪蓟肾康汤治疗HSPN的重要靶点。GO富集分析表明,芪蓟肾康汤对HSPN的治疗作用与人体的抗炎反应及血压调节等密切相关;代谢通路及KEGG分析结果都集中在人体精氨酸代谢途径上;分子对接成功验证了芪蓟肾康汤的治疗效益。结论:HSPN的发病机制与人体精氨酸代谢异常密切相关,以槲皮素为代表的化合产物可能是芪蓟肾康汤治疗HSPN的药效基础,本研究为中药复方芪蓟肾康汤治疗HSPN的内在作用机制提供了前瞻性和指导性的结果。

Objective: To explore the mechanism of Qiji Shenkang Decoction(QJD) in the treatment of purpuric nephritis(HSPN) by using techniques of metabolomics, network pharmacology and molecular docking. Methods: SIMCA and MetaboAnalyst were used to analyze the urinary metabolome information of children, and to evaluate the therapeutic effect of QJD. The potential pathogenesis and biomarkers of HSPN was analyzed. Network pharmacology was used to explore the therapeutic mechanism of QJD. The therapeutic mechanism of the core compounds of QJD was verified using AutoDock. Results:The metabolome results showed that the pathogenesis of HSPN was closely related to the abnormal changes in human arginine biosynthesis. The results of network pharmacology showed that quercetin, luteolin, kaempferol, formononetin and isorhamnetin were the important components of QJD, and PTGS2, PTGS1, F2, ESR1 and PRSS1 were the important targets for QJD to treat HSPN. GO enrichment analysis shows that the therapeutic effect of QJD on HSPN was closely related to the human body’s antiinflammatory response and blood pressure regulation. The metabolic pathway and KEGG analysis results were concentrated on the human arginine metabolic pathway. Molecular docking successfully verified QJD the therapeutic benefits. Conclusion:The pathogenesis of HSPN is closely related to the abnormal metabolism of arginine in humans, and that the chemical synthesis products represented by quercetin may be the basis of the pharmacological effect of QJD in the treatment of HSPN. This study provides prospective and guiding findings on the intrinsic mechanism of action of the Chinese herbal medicine compound QJD in treating HSPN.