基于网络药理学探讨补肾强督治偻方治疗强直性脊柱炎的作用机理

Mechanism of Bushen Qiangdu Zhilou Decoction(补肾强督治偻方) in Treating Ankylosing Spondylitis Based on Network Pharmacology

目的通过网络药理学方法探讨补肾强督治偻方治疗强直性脊柱炎的作用机理。方法运用中药系统药理学成分分析平台(BAT-MAN)数据库获取补肾强督治偻方的作用靶标基因,于CTD数据库中获取强直性脊柱炎疾病相对应的靶标基因,将两者取交集后获取疾病-药物蛋白靶基因,运用网络可视化软件STRING构建蛋白质间相互作用网络,并将结果进行网络可视化展示,通过网络结构和节点间加权重联系的计算分析算法筛选出重要的关键基因。借助DAVID在线工具进行疾病-药物交集靶基因的基因本体论(GO)分析和KEGG通路富集分析。最后在CTD数据库中获取关键基因于强直性脊柱炎的疾病治疗作用。结果补肾强督治偻方靶标基因与强直性脊柱炎疾病靶标基因的交集基因有705个。GO分析结果显示,补肾强督治偻方-强直性脊柱炎交集靶基因的生物功能主要包括基因表达的阳性调控、炎症反应、细胞增殖阳性调控等;信号通路富集结果显示,补肾强督治偻方-强直性脊柱炎交集靶基因的网络主要涉及肿瘤坏死因子信号通路、雌激素信号通路、T细胞受体信号通路等。获得关键基因23个,都与痛症、炎症性疾病及关节炎性疾病相关。结论补肾强督治偻方治疗强直性脊柱炎是多靶点、多通路、多选择的复杂机制过程,其机制多与抗炎和镇痛相关。

Objective To explore the mechanism of Bushen Qiangdu Zhilou Decoction（补肾强督治偻方） in treating ankylosing spondylitis（ AS） by network pharmacology methods. Methods The target genes of Bushen Qiangdu Zhilou Decoction were obtained in pharmacology component analysis platform of Chinese medicine system（ BAT-MAN）. The Target genes corresponding to AS were obtained in the Comparative Toxicogenomics Database（ CTD）. The target genes of the disease-drug protein were obtained after the intersection of the fore-mentioned two target genes. The interprotein interaction network was constructed by network visualization software STRING and the results were showed by network visualization. The important key genes were screened by calculation and analysis algorithm of network structure and inter node weighting connection. Gene ontology（ GO） analysis of disease-drug intersection target genes and KEGG pathway enrichment analysis were made by DAVID on line tools. At last,the therapeutic effect of key genes in AS was obtained in CTD. Results There were 705 intersection genes of Bushen Qiangdu Zhilou Decoction target genes and AS disease target genes. GO analysis results showed that the biological function of intersection target genes of Bushen Qiangdu Zhilou Decoction and AS mainly included positive regulation of gene expression and inflammatory reaction,as well as positive regulation of cell proliferation. The signal pathway enrichment results showed that the network of intersection target genes of Bushen Qiangdu Zhilou Decoction and AS mainly involved Tumor necrosis factor signal pathway,estrogen signal pathway and T cell receptor signal pathway.Twenty-three key genes were obtained,which related to pain,inflammatory diseases,and arthritis. Conclusion Bushen Qiangdu Zhilou Decoction treating AS is a multi target,multi path,and multi choice process with complex mechanism. The mechanism might be related to anti-inflammatory and analgesic.