基于网络药理学探讨红萸饮治疗溃疡性结肠炎的分子机制
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国家自然科学基金青年基金项目(81202696);上海中医药大学研究生创新培养专项(Y201920)


Mechanism of Hongyu Drink in the Treatment ofUlcerative Colitis Based on Network Pharmacology
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    摘要:

    目的:采用网络药理学的方法,对红萸饮(HYY)治疗溃疡性结肠炎(UC)的作用机制进行探讨。方法:通过TCMSP平台和Uniprot数据库对HYY进行活性成分及作用靶点筛选和标准化;在Genecards和在线人类孟德尔遗传数据库中获取疾病靶点。采用Draw Venny Diagram程序生成药物活性成分-疾病靶点数据集及韦恩图;String网站生成蛋白-蛋白互作网络图;Cytoscape 3.7.2软件构建成分-靶点网络;利用R3.6.0软件进行GO功能注释和KEGG通路富集分析。实验通过DSS建立C57 UC小鼠模型,利用HE染色、酶联免疫吸附试验(ELISA)、qPCR检测来进一步验证。结果:共筛选出HYY 4味药所含50种类药成分;预测出110个潜在靶点;其中UC相关靶点共计3 870个;HYY-疾病共同靶点70个,主要富集于88个生物过程和113条信号通路上。实验也表明HYY可改善UC模型结直肠上皮完整性,降低血清IL-6和结直肠VEGF基因表达。结论:结合实验分析HYY可能通过调节CASP3、IL-6、VEGFA等靶点,调控PI3K-Akt等信号通路,从而调控细胞凋亡、血管生成,抑制炎性反应来达到对UC的治疗作用。

    Abstract:

    To explore the mechanism of the action of Hongyu Drink (HYD) in the treatment on ulcerative colitis (UC) by network pharmacology.Methods:The active ingredients and targets of HHD were screened by TCMSP platform,and the targets' name of the selected targets were standardized by Uniprot database.The search was performed in Genecards database and online human Mendelian genetic database to obtain disease target points.The Draw Venny Diagram online program was used to generate the pharmaceutically active ingredient-disease target data set and the Venn diagram.Protein-protein interaction network map was generated by using String website; component-target network was constructed by using Cytoscape 3.7.2 software; GO function annotation and KEGG pathway enrichment analysis were performed by R3.6.0 software.The C57 UC mouse model was established by DSS,and HE staining、ELIS、qPCR were used to verify the results of network pharmacology detection.Results:A total of 50 kinds of drug components were included in the 4 herbs of HHY; 110 potential targets were predicted; the total number of UC-related disease targets was 3870; a total of 70 common targets of Pulsatilla chinensis-disease were obtained,and the co-targets were mainly enriched in 88 biological processes and 113 signaling pathways.The experimental results showed that HYDin can improve the colorectal epithelial integrity of UC animal model and reduce the expression of VEGF mRNA in serum IL-6 and colorectal tissues.Conclusion:Combined with experiment,network pharmacology analysis shows that HYDin may regulate the CASP3,IL-6,VEGFA,et al,and PI3K-Akt signaling pathway,et al,which regulates apoptosis,angiogenesis and inhibition of inflammation,achieves a therapeutic effect on ulcerative colitis.Other pathways need our further study.

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张馨心,周唯,陆金根,王佳雯,潘一滨,许言午.基于网络药理学探讨红萸饮治疗溃疡性结肠炎的分子机制[J].世界中医药,2021,(01).

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  • 收稿日期:2020-02-24
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  • 在线发布日期: 2021-01-26
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