摘要
目的:基于网络药理学挖掘并预测四君子汤与痛泻要方同病异治抗溃疡性结肠炎(UC)的作用靶点及相关信号通路,并研究其作用机制。方法:GEO数据库筛选UC患者差异表达基因;中药系统药理学数据库与分析平台(TCMSP)获得复方化学成分及对应靶点;构建中药复方调控网络;绘制蛋白质-蛋白质相互作用(PPI)网络,预测核心基因;进行富集分析。用葡聚糖硫酸钠(DSS)诱导UC小鼠模型,小鼠随机分为正常组、UC组、四君子汤组、痛泻要方组与美沙拉嗪组,连续给药14 d,进行疾病活动指数(DAI)评分;测算血液流变学特征值;检测血清白细胞介素-6(IL-6)、组织因子(TF)、缺氧诱导因子-1α(HIF-1α)含量变化;测算核转录因子(NF)-κB抑制因子蛋白激酶α(IKKα)、NF-κB、HIF-1α、血管内皮细胞生长因子(VEGF)mRNA的相对表达量。结果:通过网络药理学分析获得两复方与UC交集基因共44个,包含17个共性基因。HIF-1通路、缺氧反应等为两复方治疗UC潜在共性靶点。结果显示两复方能够显著降低DAI评分;显著提高血流灌注量、血细胞移动速度,降低移动红细胞浓度;显著降低IL-6、TF、HIF-1α的水平;显著降低IKKα、NF-κB、HIF-1α、VEGF mRNA的表达量。结论:HIF-1通路及相关靶标可能为两复方发挥同病异治作用的共性靶点,四君子汤长于行气改善肠组织缺氧状态,痛泻要方长于活血促进肠黏膜微循环。
Objective:To predict the targets and signaling pathways of Si Junzitang and Tongxie Yaofang in treating ulcerative colitis(UC)following the concept of"same disease with different treatments"based on the network pharmacology and explore the underlying mechanisms.Method:The differentially expressed genes(DEGs)of UC were extracted from GeoChip.The active components and corresponding potential targets of Si Junzitang and Tongxie Yaofang were collected from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP).The regulatory networks of Si Junzitang and Tongxie Yaofang were constructed and the protein-protein interaction(PPI)network was plotted.The core genes were predicted,followed by enrichment analysis.The UC model was induced in mice by dextran sodium sulfate(DSS)solution.Mice were randomly divided into a normal group,a UC group,a Si Junzitang group,a Tongxie Yaofang group,and a mesalazine group.Drugs were administered continuously for 14 days.The disease activity index(DAI)was scored for mice in each group.The characteristic values of hemorheology were measured.The serum levels of interleukin-6(IL-6),tissue factor(TF),and hypoxia-inducible factor-1α(HIF-1α)in mice were detected.The relative mRNA expression levels of inhibitory kappa B kinaseα(IKKα),nuclear factor kappa B(NF-κB),HIF-1α,and vascular endothelial growth factor(VEGF)were measured.Result:A total of 44 genes were obtained by network pharmacological analysis,including 17 common genes.HIF-1 pathway and hypoxia response were potential common targets of Si Junzitang and Tongxie Yaofang in the treatment of UC.The results showed that Si Junzitang and Tongxie Yaofang could significantly reduce DAI score,increase blood perfusion volume and blood cell movement speed,decrease the concentration of mobile red blood cells,reduce the levels of IL-6,TF,and HIF-1α,down-regulate the mRNA expression of IKKα,NF-κB,HIF-1α,and VEGF.Conclusion:The HIF-1 pathway and related targets may be the common targets of Si Junzitang and T
作者
李鸿
于官正
胡雪黎
杨宝
涂星
LI Hong;YU Guanzheng;HU Xueli;YANG Bao;TU Xing(Medical School,Hubei Minzu University,Enshi 445000,China;Chinese Medicinal Materials Products Quality Supervision and Inspection Center in Wuling Mountainous Area,Hubei Minzu University,Enshi 445000,China)
出处
《中国实验方剂学杂志》
CAS
CSCD
北大核心
2023年第3期52-60,共9页
Chinese Journal of Experimental Traditional Medical Formulae
基金
国家自然科学基金地区科学基金项目(82160804)
湖北民族大学2022年揭榜挂帅科研项目(JB22003)。
关键词
网络药理学
四君子汤
痛泻要方
溃疡性结肠炎
同病异治
network pharmacology
Si Junzitang
Tongxie Yaofang
ulcerative colitis
same disease with different treatments
