基于网络药理学探究苏黄泻浊丸抗肾间质纤维化及其调控铁死亡的作用机制

A study on the mechanism of Suhuang Xiezhuo Wan in the treatment of renal interstitial fibrosis and regulation of ferroptosis based on network pharmacology

目的:基于网络药理学探究苏黄泻浊丸治疗肾间质纤维化(Renal Interstitial Fibrosis,RIF)及调控铁死亡的作用机制。方法:通过中药系统药理学数据库与分析平台(TCMSP)、STRING、OMIM、Gene Cards、DisGeNet等筛选苏黄泻浊丸的中药活性成分及RIF关联靶标,借助Cytoscape 3.6.0软件构建苏黄泻浊丸活性成分-RIF靶标网络,结合STRING数据库构建方药与RIF关联靶点蛋白质-蛋白质相互作用网络,利用DAVID数据库进行京都基因与基因组百科全书(KEGG)通路富集分析;利用FerrDb数据库获取铁死亡调控基因,最终获取公共靶标基因,构建苏黄泻浊丸活性成分-RIF、铁死亡共同靶标网络,结合STRING数据库构建共同靶蛋白相互作用网络;利用DAVID数据库进行KEGG通路富集分析。结果:筛选出药物活性成分102个,与RIF关联的靶基因177个,经基因本体论(GO)、KEGG分析,苏黄泻浊丸治疗RIF的生物过程与RNA聚合酶Ⅱ促进转录的正调控、转录因子活性、序列特异性DNA结合等有关,通过调节脂质与动脉粥样硬化、白细胞介素(Interleukin,IL)-17信号通路、肿瘤坏死因子(Tumor Necrosis Factor,TNF)信号通路、磷脂酰肌醇3激酶(Phosphatidylinositol 3-kinase,PI3K)-蛋白激酶B(Akt)信号通路、辅助性T细胞17(T Helper Cells 17,Th17)细胞分化、细胞衰老发挥作用。调控铁死亡共同基因有34个,可能参与IL-17信号通路、缺氧诱导因子-1(Hypoxia Inducible Factor-1,HIF-1)信号通路、ErbB信号通路、脂质代谢、Th17细胞分化、C型凝集素受体信号通路、TNF信号通路等。结论:本研究预测了苏黄泻浊丸治疗RIF及其调控铁死亡的主要化合物、靶标及通路,为后续深入研究苏黄泻浊丸治疗RIF的作用机制提供理论参考。

Objective:To investigate the mechanism of action of Suhuang Xiezhuo Wan(苏黄泻浊丸)in the treatment of renal interstitial fibrosis(RIF)and regulation of ferroptosis based on network pharmacology.Methods:The TCMSP,STRING,OMIM,Gene Cards and DisGeNet were used to screen the active ingredients and RIF targets of Suhuang Xiezhuo Wan.The active ingredient of Suhuang Xiezhuo Wan-RIF target network was constructed by Cytoscape 3.6.0 software.The interaction network between the prescription and the RIF targets was constructed by STRING database.The enrichment analysis of KEGG was carried out by DAVID database.FerrDb database was used to obtain the ferroptosis-regulating genes,and finally the common target genes were obtained to construct the active ingredient of Suhuang Xiezhuo Wan-RIF and ferroptosis genes network.STRING database was used to construct the common target protein-protein interaction network,and KEGG analysis was carried out by the DAVID database.Results:A total of 102 active ingredients and 177 RIF-associated target genes were screened.After GO and KEGG analyses,the biological process of Suhuang Xiezhuo Wan in the treatment of RIF was related to the positive regulation of RNA polymerase II to promote transcription,the activity of transcription factors and sequence-specific DNA binding and so on,and it could play roles in the regulation of the lipids and atherosclerosis,the IL-17 signaling pathway,the TNF signaling pathway,the PI3K-Akt signaling pathway,the Th17 cell differentiation,and cellular senescence.There are 34 common genes regulating ferroptosis,which may be involved in IL-17 signalling pathway,HIF-1 signalling pathway,ErbB signalling pathway,lipid metabolism,Th17 cell differentiation,C-type lectin receptor signalling pathway,and TNF signalling pathway.Conclusion:This study predicted the main compounds,targets and pathways of Suhuang Xiezhuo Wan on RIF and its regulation of ferroptosis,providing theoretical references for the subsequent in-depth study of the mechanism of action of Suhuang Xiezhuo Wan on RIF.