基于网络药理学和分子对接技术探讨固肠止泻丸治疗溃疡性结肠炎的分子机制  

Mechanism of Guchang Zhixie Pill(固肠止泻丸)in Treatment of Ulcerative Colitis Based on Network Pharmacology and Molecular Docking

作　　者：张聪伟 刘力[2] 杜晓泉 梁艳妮[3] 吕小龙 ZHANG Congwei;LIU Li;DU Xiaoquan;LIANG Yanni;LYU Xiaolong(Affiliated Hospital of Shaanxi University of Chinese Medicine,Xianyang 712000,Shaanxi,China;Shaanxi University of Chinese Medicine,Xianyang 712046,Shaanxi,China;Shaanxi Collaborative Innovation Center of Chinese Medicinal Resources Industrialization,Shaanxi University of Chinese Medicine,Xianyang 712000,Shaanxi,China;Shaanxi Provinical Hospital of Chinese Medicine,Xi’an 710003,Shaanxi,China)

机构地区：[1]陕西中医药大学附属医院,陕西咸阳712000 [2]陕西中医药大学,陕西咸阳712046 [3]陕西中医药大学中药资源产业化协同创新中心,陕西咸阳712000 [4]陕西省中医医院,陕西西安710003

出　　处：《辽宁中医杂志》2023年第4期145-150,I0003,I0004,共8页Liaoning Journal of Traditional Chinese Medicine

基　　金：国家自然科学基金青年基金项目(81803951);陕西省科技厅科研项目(2019SF-099)。

摘　　要：目的 研究旨在探讨固肠止泻丸治疗溃疡性结肠炎(UC)的作用靶点及分子机制,为临床应用提供依据。方法 利用TCMSP数据库筛选固肠止泻丸的有效成分及相关靶基因,运用生物信息学的方法分析GEO数据芯片,并结合OMIM、CTD、GeneCards、DisGeNet等数据库获取UC相关靶基因,采用Cy-toscape软件构建固肠止泻丸化学成分-靶基因-疾病调控网络,STRING数据库进行蛋白互作选取作用的核心靶基因,通过DAVID数据库对靶点相关的基因功能和信号通路进行分析,预测固肠止泻丸治疗UC的潜在靶基因。结果 固肠止泻丸的6味中药共87个活性成分和1960个靶基因,GEO芯片数据分析UC相关靶基因得出180个差异靶基因,结合OMIM、CDT等疾病数据库共得出1081个UC相关靶基因,其中IL6、TP53、MAPK8、VEGFA、EGFR、IL10等15个靶基因可能是固肠止泻丸治疗UC的关键靶基因;固肠止泻丸可能通过TNF信号通路、NF-κB信号通路、细胞凋亡信号通路、PI3K/Akt信号通路、MAPK信号通路等通路,发挥抗炎、促进炎性细胞凋亡、修复受损黏膜,以达到治疗UC目的。且虚拟分子对接显示槲皮素、罂粟碱、β-谷甾醇等化合物与IL-6、MAPK8、VEGFA等核心靶基因等结合较好,可能是固肠止泻丸治疗UC的主要药效物质基础。结论 固肠止泻丸可能通过多组分、多靶基因和多通路协同作用发挥抗炎、促进炎性细胞凋亡、修复受损黏膜的作用,从而治疗UC。Objective The study aimed to investigate the target and intrinsic mechanisms of Guchang Zhixie Pill(固肠止泻丸)in the treatment of ulcerative colitis(UC)and provide evidence for its clinical application.Methods TCMSP database was used to screen the effective components and related target genes of Guchang Zhixie Pills.Bioinformatics method was used to analyze GEO data chip.OMIM,CTD,GeneCards,DisGeNet and other databases were used to obtain UC-related target genes.The Cy-toscape software constructed the chemical composition-target gene-disease regulation network of Guchang Zhixie Pill.STRING base was used to select the core target gene of protein interaction.The gene function and signal pathway related to the target were analyzed through DAVID database and the potential target gene of Guchang Zhixie Pill treating UC was predicted.Results There were 87 active components and 1960 target genes of Guchang Zhixie Pill.A total of 180 differential target genes were obtained by analyzing UC related target genes with GEO chip data.A total of 1081 UC related target genes were obtained by combining OMIM,CDT and other disease data databases.Among them,15 target genes,such as IL6,TP53,MAPK8,VEGFA,EGFR and IL10,may be the key target genes of Guchang Zhixie Pill treating UC.Guchang Zhixie Pill may play the role of anti-inflammatory,promoting apoptosis of inflammatory cells and repairing damaged mucosa through TNF signaling pathway,NF-κB signaling pathway,apoptosis signaling pathway,PI3K/Akt signaling pathway and MAPK signaling pathway.Moreover,virtual and molecular docking showed that quercetin,papaverine,β-sitosterol and other core target genes such as IL6,MAPK8 and VEGFA were well combined,which may be the main pharmacodynamic material basis of Guchang Zhixie Pill in the treatment of UC.Conclusion Guchang Zhixie Pill may play the role of anti-inflammatory,promoting apoptosis of inflammatory cells and repairing damaged mucosa through the synergistic effect of multi-component,multi-target gene and multi-channel,so as to tr

关 键 词：固肠止泻丸 溃疡性结肠炎 网络药理学 生物信息学 虚拟分子对接 作用机制 

分 类 号：R574.62[医药卫生—消化系统]