基于网络药理学研究消瘀泄浊饮治疗慢性肾功能衰竭的作用机制
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R692.5

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浙江省中医药科技计划(2019ZQ021);浙江省中医药科技计划(2020ZB075);马红珍名老中医专家传承工作室(GZS2017006)


Study on Action Mechanism of Xiaoyu Xiezhuo Yin for Chronic Renal Failure Based on Network Pharmacology
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    摘要:

    目的:利用网络药理学方法研究消瘀泄浊饮治疗慢性肾功能衰竭(Chronic Renal Failure,CRF)的分子机制。方法:采用TCMSP 与化学专业数据库及文献收集消瘀泄浊饮的有效活性成分和作用靶点。在GeneCards、OMIM、DrugBank、TTD 数据库中获得CRF 相关靶点,对消瘀泄浊饮药物靶点和CRF 相关基因取交集。使用Cytoscape 3.7.2 软件构建“药物活性成分-CRF-靶点”网络,将交集靶点导入STRING 数据库,构建蛋白质相互作用网络(PPI),借助Metascape 在线工具对关键靶点进行GO 功能富集分析、KEGG 通路富集分析,并用Autodock vina 和Chimera-1.14 软件对蛋白和活性成分进行分子对接。结果:通过筛选获得消瘀泄浊饮主要活性成分68 个,249 个靶点基因;CRF 相关基因共1 533 个;交集靶点101 个。消瘀泄浊饮治疗CRF 的关键靶点为黄芪、川牛膝、车前草的共同主要成分AKT1,IL-6,以及大黄、黄芪、桃仁、川牛膝、车前草的共同主要成分PTGS2 等。KEGG 富集分析筛选出包括HIF-1 信号通路、PI3K/Akt 信号通路、NF-κB 信号通路、JAK-STAT 信号通路在内的185 条通路,生物过程主要涉及对氧化应激的反应、凋亡、活性氧代谢等。分子对接结果显示,消瘀泄浊饮中槲皮素、木犀草素、芦荟大黄素等关键化合物与IL-6、PTGS2 等关键靶点有较好的结合能力。结论:消瘀泄浊饮治疗CRF 的作用机制可能是通过槲皮素、木犀草素、芦荟大黄素等活性成分,经HIF-1、PI3K/Akt、NF-κB、JAK-STAT 等信号通路,作用于IL-6、PTGS2 以调节细胞凋亡、氧化应激、脂多糖反应、活性氧代谢等多个生物过程,最终达到延缓CRF 进展的作用。

    Abstract:

    Abstract:Objective:To study the molecular mechanism of Xiaoyu Xiezhuo yin for chronic renal failure (CRF) by network pharmacology. Methods:The TCMSP,chemical database and literature were applied to collect active ingredients and action targets of Xiaoyu Xiezhuo yin. The CRF- related targets were obtained from GeneCards,OMIM,DrugBank and TTD databases,and the intersection of targets of Xiaoyu Xiezhuo yin and CRF-related genes was obtained. The Cytoscape 3.7.2 software was used to establish the “active pharmaceutical ingredients- CRF- targets” network;the intersection targets were imported into STRING database to establish the protein- protein interaction network(PPI); Metascape online tool was used to conduct GO function enrichment analysis and KEGG pathway enrichment analysis for key targets;Autodock vina and Chimera-1.14 software were used for molecular docking of proteins and active ingredients. Results: A total of 68 main active ingredients and 249 target genes of Xiaoyu Xiezhuo yin were obtained by screening;there were 1,533 CRF-related genes,and 101 intersection targets. The key targets of Xiaoyu Xiezhuo yin for CRF are AKT1 and IL- 6, which were the common main components of Radix Astragali, Radix Achyranthis Bidentatae and Herba Plantaginis, as well as PTGS2, which was the common main component of Radix et Rhizoma Rhei,Radix Astragali,Semen Persicae,Radix Achyranthis Bidentatae and Herba Plantaginis. KEGG enrichment analysis screened out 185 pathways including HIF- 1 signaling pathway, PI3K/Akt signaling pathway,NF-κB signaling pathway and JAK-STAT signaling pathway;biological processes mainly involved in oxidative stress response, apoptosis, active oxygen metabolism, etc. The results of molecular docking showed that the key compounds in Xiaoyu Xiezhuo yin,such as quercetin,luteolin and aloe- emodin , had a good binding ability to IL- 6 , PTGS2 and other key targets. Conclusion : The mechanism of Xiaoyu Xiezhuo yin in treating CRF can be through quercetin, luteolin, aloe- emodin and other active ingredients,and through HIF-1,PI3K/Akt,NF-κB,JAK-STAT and other signaling pathways to act on IL-6 and PTGS2 to regulate apoptosis,oxidative stress,lipopolysaccharide reaction,active oxygen metabolism and other biological processes, and finally achieves the effect of delaying the progression of CRF.

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丁越越,孙华洁,陈文文,陈智渊,叶晴晴,马红珍.基于网络药理学研究消瘀泄浊饮治疗慢性肾功能衰竭的作用机制[J].新中医,2022,54(16):1-8

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  • 在线发布日期: 2022-08-28
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