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

张馨心 周唯 陆金根 王佳 潘一滨 许言午

摘要 目的：采用網络药理学的方法，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。

关键词 红萸饮;网络药理学;溃疡性结肠炎;炎性反应;凋亡;血管生成

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

ZHANG Xinxin1，ZHOU Wei1，LU Jin′gen1，WANG Jiawen1，PAN Yibin1，XU Yanwu2

（1 Longhua Hospital of Shanghai University of Traditional Chinese Medicine，Shanghai 200032，China; 2 College of Basic Medicine of Shanghai University of Traditional Chinese Medicine，Shanghai 200032，China）

Abstract Objective：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.

Keywords Hongyu Decoction; Network pharmacology; Ulcerative colitis; Inflammation; Apoptosis; Angiogenesis

中图分类号：R285;R284文献标识码：Adoi：10.3969/j.issn.1673-7202.2021.01.009

溃疡性结肠炎（Ulcerative Colitis，UC）是一种病因尚不十分清楚的结肠和直肠慢性非特异性炎症性疾病。病变部位多位于乙状结肠和直肠，也可延伸至降结肠，甚至整个结肠。UC病程漫长，常反复发作，严重影响患者的生命质量。2015年世界胃肠组织（World Gastroenterology Organization，WGO）发布的《炎症性肠病全球指南》显示UC在北欧、英国和北美的高患病率已趋于保持稳定，而在南欧、亚洲和大多数发展中国家，原本较低的患病率正在升高[1]。……