复方紫草油治疗唇炎机制的网络药理学研究

任雪雯 李元文 蔡玲玲 肖飞 陈艳明

摘要  目的：利用網络药理学的技术探索复方紫草油治疗唇炎的机制，为后续实验研究及扩大复方紫草油的适应证提供理论基础。方法：依托中药系统药理学平台（TCMSP）、中药综合数据库（TCMID）筛选复方紫草油的有效化合物和作用靶点;通过检索人类基因信息数据库（GeneCards）及人类孟德尔遗传研究平台（OMIM）选取唇炎的疾病靶点，并利用R语言取疾病与药物靶点交集;应用Cytoscape软件构建药物-化合物-靶点-疾病互作网络;运用STRING平台搭建蛋白质间相互作用网络（PPI）;使用Bioconductor生物信息软件包进行GO功能富集和KEGG通路分析。结果：筛选得103个化合物和相应115个靶点，其中有21个与疾病相关。GO功能富集分析得到22个条目，KEGG通路富集分析筛选得到91条信号通路。结论：复方紫草油治疗唇炎具有生物学支撑。不同的蛋白存在协同作用，其中IL-6、STAT3和TNF等靶点起着关键作用。生物过程主要涉及细胞因子受体结合、金属内肽酶活性等，并主要富集在AGE-RAGE、FssAs和TNF等多条信号通路上，发挥抗炎及调控细胞增殖和凋亡等作用。

关键词  网络药理学;复方紫草油;唇炎;抗炎机制;信号通路

Network Pharmacology Study on the Mechanism of Compound Oleum Lithospermi in the Treatment of Cheilitis

REN Xuewen1，LI Yuanwen1，CAI Lingling1，XIAO Fei2，CHEN Yanming3

（1 Dongfang Hospital，Beijing University of Chinese Medicine，Beijing 100078，China; 2 Jianmin Group Children′s Medicine Research Institute，Wuhan 430052，China; 3 School of Pharmaceutical Science and Technology，Tianjin University，Tianjin 300072，China）

Abstract Objective： To provide a theoretical basis for the follow-up experimental research and expanding the indication of compound oleum lithospermi by using the technology of network pharmacology to explore the mechanism of compound oleum lithospermi in the treatment of cheilitis， Methods： Based on TCMSP（Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform）and TCMID（Traditional Chinese Medicine Integrative Database）to screen the effective compounds and targets of Compound Oleum Lithospermi.GeneCards（The Human Gene Database）and OMIM（Online Mendelian Inheritance in Man）was used to select the disease targets of Cheilitis.R language was used to get the intersection of disease and drug target.Cytoscape software was used to build drug-compound-target-disease interaction network; STRING platform was used to build protein-protein interaction network（PPI）; Bioconductor biological information software package was used for GO function enrichment and KEGG pathway analysis. Results： A total of 103 compounds and 115 corresponding targets were screened，of which 21 were related to diseases.GO functional enrichment analysis yielded 22 entries，and KEGG pathway enrichment analysis screening yielded 91 signal pathways. Conclusion： Compound oleum lithospermi has biological support in the treatment of cheilitis.Different proteins have synergistic effects，among which IL-6、STAT3 and TNF etc.play a key role.The biological process mainly involves cytokine receptor binding，metalloendopeptidase activity，etc.These targets are mainly concentrated in multiple signaling pathways such as AGE-RAGE、FssAs and TNF，which play key roles of anti-inflammatory and regulation of cell proliferation and apoptosis，etc.

Keywords  Network pharmacology; Compound Oleum Lithospermi; Cheilitis; Anti-inflammatory mechanism; Signaling pathway

中图分类号：R242;R285 文献标识码：A  doi： 10.3969/j.issn.1673-7202.2020.14.004

唇炎（Cheilitis），类似于中医文献记载的“唇风”“紧唇”。临床上根据症状可分为变应性接触性唇炎、光线性唇炎、剥脱性唇炎、腺性唇炎、肉芽肿性唇炎等[1]。具体表现为唇部皮肤黏膜以干燥脱屑、发痒灼痛、肿胀、渗出结痂为主，多见于下唇红肿。常有不自觉地舔唇咬唇或用手揉擦唇部，以致病损区皲裂渗出，血痂复结，肿胀明显，反复继发感染，使其病程迁延[2]。……