摘要：目的 采用“药材-成分-靶点-通路”关联网络分析方法探索我院自拟排石汤治疗泌尿系统结石的作用机制。方法 基于中药分子机制的生物信息学分析工具平台（BATMAN）数据库检索排石汤的9味药材（金钱草、海金砂、王不留行、益母草、郁金、车前子、丹参、怀膝、生甘草）化学成分和作用靶点；查询Gennecards、DisGenet数据库泌尿系结石的相关靶点；筛选排石汤和泌尿系结石的交集靶点并寻找蛋白互作网络；在cytoscape中筛选蛋白互作网络的核心靶点，对核心靶点进行GO和KEGG富集分析以探寻排石汤治疗泌尿系统的潜在机制。结果 以Score cutoff >39且P<0.05 作为筛选条件，筛选排石汤 124个活性成分和571个靶点，与泌尿系统结石相关的靶点140个，包括27个核心靶点，例如PTGS2，PDE5A，GSTP1，NQO1，PTGS2，F2，TNF等，此外，丹参酮Ⅵ，γ-谷固醇，甘草次酸，亚油酸，亚麻酸等为核心化合物。GO富集得出869条结果，其中生物过程790条，包括多细胞生物过程的调控，对含氧化合物的反应，细胞外空间等；细胞组成18条，包括内膜系统，细胞外泌体，高尔基内腔等；分子功能61条，例如抗氧化活性，分子功能调节因子，核受体活性等。KEGG通路富集得相关通路103条，结果显示排石汤可显著调节TNF信号通路（TNF signaling pathway），破骨细胞分化（Osteoclast differentiation），肾素-血管紧张素系统（Renin-angiotensin system），Toll样受体信号通路（Toll-like receptor signaling pathway）等多条通路发挥治疗作用。分子对接验证结果显示排石汤的脂肪酸类化合物与核心靶点的残基可以自由结合。结论 通过网络药理学初步探讨了排石汤多成分、多靶点、整体调节的作用特点，预测了排石汤可能通过抗炎和抗氧化应激等方面治疗泌尿系结石，本研究为排石汤的活性成分生物学机制研究提供理论依据。

Abstract: [Objective] The " herbs-component-target-pathway" correlation network analysis method was used to explore the mechanism of self-made Paishi Decoction in the treatment of urolithiasis. [Method] Based on the bioinformatics analysis tool for molecular mechanism of traditional Chinese medicine (BATMAN) database, search the chemical composition and target of the 9 herbs of Paishi Decoction (christina loosestrife, Japanese climbing fern, Cowherb, wormwood-like motherwort equivalent, aromaticturmeric, seed of asiatic pantain, danshen equivalent, twotooth achyranthes, ural licorice equivalent), query the related targets of urolithiasis in Gennecards and DisGenet databases; screen Paishi Decoction and urolithiasis the intersection targets and find the protein interaction network; screen the core targets of the protein interaction network in cytoscape, and perform GO and KEGG enrichment analysis on the core targets to explore the potential mechanism of Paishi Decoction to treat the urolithiasis. [Results] With Score cutoff >39 and P<0.05 as the screening principle, 124 components and 571 targets of Paishi Decoction were screened, 140 targets related to urolithiasis, including 27 core targets, such as PTGS2, PDE5A, GSTP1, NQO1, PTGS2, F2, TNF, etc., in addition, tanshinone VI, γ-sitosterol, glycyrrhetinic acid, linoleic acid, linolenic acid, etc. are the core compounds. GO enrichment yielded 869 results, of which 790 were biological processes, including the regulation of multicellular biological processes, response to oxygenated compounds, extracellular space, etc.; cells composed of 18, including the endometrial system, exosomes, Golgi lumen, etc.; 61 molecular functions, such as antioxidant activity, molecular function regulators. The KEGG pathway is enriched with 103 related pathways. The results show that Paishi Decoction can significantly regulate TNF signaling pathway, osteoclast differentiation, renin-angiotensin system, toll-like receptor signaling pathway and other pathways to play a therapeutic role. The results of molecular docking show that the fatty acid compounds of Paishi Decoction can freely bind to the residues of the core target. [Conclusion] Through network pharmacology, the characteristics of the multi-component, multi-target, and overall regulation of Paishi Decoction are preliminarily discussed, and it is predicted that Paishi Decoction may treat urolithiasis through anti-inflammatory and antioxidant stress aspects. This study is the activity of Paishi Decoction The research on the biological mechanism of the components provides a theoretical basis.

包头市科技计划项目