摘要
目的基于网络药理学预测并通过动物实验验证探究芍药汤治疗溃疡性结肠炎(UC)湿热内蕴证的潜在作用机制。方法运用TCMSP、UniProt数据库筛选芍药汤活性成分及相关靶点,利用GEO数据库筛选UC疾病靶点。将药物靶点与疾病靶点匹配所得交集靶点导入STRING数据库构建蛋白相互作用(PPI)网络,借助Cytoscape3.7.0软件构建药物-化合物-疾病靶点网络。使用R语言对交集基因进行GO及KEGG通路富集分析。建立UC湿热内蕴证大鼠模型并用芍药汤进行干预,对核心靶点及相关通路进行初步验证。对大鼠进行疾病活动指数(DAI)评分,HE染色观察结肠组织病理学改变,ELISA检测血清炎症因子白细胞介素(IL)-6、IL-1β含量,Western blot检测结肠组织NF-κBp65、MMP9、STAT3表达,免疫组化法检测结肠组织NF-κBp65表达。结果筛选出芍药汤治疗UC的有效成分141种,作用靶点69个,PPI网络拓扑分析获得10个核心基因,通过GO及KEGG富集分析得到芍药汤干预UC的关键信号通路。动物实验结果表明,芍药汤可降低模型大鼠血清炎症因子IL-6、IL-1β含量,抑制NF-κBp65、MMP9、STAT3表达。结论芍药汤可能通过调控IL-6、IL-1β、MMP9、STAT3等靶点,及干预NF-κB信号通路,治疗UC湿热内蕴证。
Objective To explore the mechanism of Shaoyao Decoction in the treatment of damp-heat ulcerative colitis(UC)based on network pharmacology prediction and animal experiment verification.Methods TCMSP and UniProt database were used to screen the active components and related targets of Shaoyao Decoction,and GEO database was used to screen disease targets of UC.The intersection targets obtained by matching drug targets and disease targets were imported into STRING to construct PPI network,and drug-compound-disease target network was constructed with Cytoscape 3.7.0 software.GO enrichment analysis and KEGG pathway enrichment analysis were performed using R language.An animal model of damp-heat UC rat was established and intervened with Shaoyao Decoction to preliminarily verify the core targets and related pathways.DAI score was performed during the administration period after modeling.HE staining was used to observe the pathological changes of colon.ELISA was used to detect the effect of Shaoyao Decoction on the serum inflammatory factors IL-6 and IL-1β.Western blot was used to detect the expressions of NF-κBp65,MMP9,STAT3 in colonic tissue;immunohistochemistry was used to detect the expression of NF-κBp65 in colonic tissue.Results In this study,141 active components of Shaoyao Decoction in the treatment of UC were screened,and 69 targets were used.PPI network topological analysis were used to obtain 10 core genes,and the key signaling pathways of Shaoyao Decoction in treating UC were obtained by GO and KEGG enrichment analysis.The results of animal experiments showed that Shaoyao Decoction could treat UC by reducing the contents of inflammatory factors IL-6 and IL-1β,and inhibiting the expressions of NF-κBp65,MMP9 and STAT3.Conclusion Shaoyao Decoction may regulate the expressions of IL-6,IL-1β,MMP9,STAT3 and other targets,and interfere with the NF-κB signaling pathway,in order to treat damp-heat UC.
作者
芦易
刘起立
李嫣红
刘星赐
吴东升
谢念佳
阳玉婷
曹晖
LU Yi;LIU Qili;LI Yanhong;LIU Xingci;WU Dongsheng;XIE Nianjia;YANG Yuting;CAO Hui(Hunan University of Chinese Medicine,Changsha 410208,China;The First Hospital of Hunan University of Chinese Medicine,Changsha 410007,China)
出处
《中国中医药信息杂志》
CAS
CSCD
2023年第6期34-41,共8页
Chinese Journal of Information on Traditional Chinese Medicine
基金
湖南省“神农人才”工程第一批中医药学科带头人培养计划(2022年)
湖南省中医药科研计划项目(2021022)
长沙市自然科学基金(kq2014221)
湖南省卫健委科研课题(202204134275)
湖南中医药大学中医学一流学科开放基金(2021ZYX26)
湖南省研究生科研创新项目(CX20210725)。
