基于网络药理学研究保肾排毒汤治疗脓毒症合并急性肾损伤的治疗机制

Study on the Underlying Mechanism of Baoshen Paidu Decoction in Sepsis and Acute Kidney Injury Treatment Based on Network Pharmacology

关键词:  脓毒症  急性肾损伤  保肾排毒汤  网络药理学  成分

Key words:  sepsis  acute kidney injury  Baoshenpaidu decoction  network pharmacology  ingredients

摘要:

目的 应用网络药理学的方法，研究保肾排毒汤治疗脓毒症及其并发症急性肾损伤的药效成分、作用靶点及作用通路，从而揭示其潜在的治疗机制。方法 利用中药相关权威数据库（TCMSP、TCMID、TCM-Mesh）并结合ADME参数和参考文献，对保肾排毒汤中的有效成分进行筛选，并通过SwissTargetPrediction和STITCH数据库预测得到成分相关靶点。通过TTD、Drugbank、OMIM、DisGeNET得到脓毒症及急性肾损伤相关靶点。成分靶点与疾病靶点取交集后得到药效成分治疗疾病的潜在靶点。应用STRING数据库构建靶点间的蛋白互作网络，通过Cytoscape软件对网络进行拓扑属性分析和功能模块分析。采用Cytoscape软件的ClueGO插件分析这些靶点富集的基因功能和代谢通路。最后构建保肾排毒汤成分-靶点-通路网络图。结果 从保肾排毒汤中筛选出56个活性成分，以及与脓毒症合并急性肾损伤相关的81个靶点。靶点间的蛋白互作网络筛选出了5个核心靶点ALB、TP53、VEGFA、PTGS2、EGFR、CASP3。基因功能和代谢通路分析表明这些靶点参与了对细菌来源的分子反应、炎症反应的调节、活性氧代谢过程、对异物和机械刺激的反应、凋亡过程、对血管和血管内皮细胞的正调控、中性粒细胞介导对细菌的杀伤作用，脂质代谢等生物过程，并参与到了多条病毒感染通路、多条涉及炎症反应和内皮血管的信号传导通路。而建立的成分-靶点-通路的共表达网络体现了保肾排毒汤多成分、多靶点、多通路的协同作用机制。结论 保肾排毒汤具有多成分、多靶点、多通路协同作用的特点，可通过其中的活性成分调控多个疾病相关靶点参与到抵抗病毒感染、抑制炎症反应、保护血管内皮、抗氧化应激、调节脂质代谢等相关通路发挥对脓毒症急性肾损伤的治疗作用的。

Abstract:

OBJECTIVE To explore the underlying mechanism of Baoshenpaidu decoctio(BSD) in sepsis and acute kidney injury (AKI) treatment with network pharmacology analysis. METHODS TCM related databases like TCMSP, TCMID, TCM-Mesh were applied companion with ADME and literature references to screen active ingredients of BSD. Targets of BSD for sepsis and AKI treatment were selected from the overlapping of the predicted targets for ingredients and the obtained targets of the disease. The protein-protein interaction (PPI) network of the targets was constructed by STRING and analyzed by Cytoscape. Clue GO tool in Cytoscape were used to analyze the gene function and KEGG pathway of the targets, and to construct the main drug ingredients-target-pathway network of BSD. RESULTS The 56 main drug ingredients of BSD and 81 related targets for disease treatment were screened from the database analysis. Six hub targets ALB, TP53, VEGFA, PTGS2, EGFR, CASP3 were selected from the PPI network. Gene functional and KEGG pathway analysis showed that these targets were related with virus infection, inflammatory response, reactive oxygen species metabolic, apoptotic process, vascular process in circulatory system, vascular endothelium cells, neutrophil mediated killing of bacterium. Main drug ingredients-targets-pathways network of BSD revealed a multiple-ingredients, multiple-targets, multiple pathways synergistic mechanism. CONCLUSION BSD may play a therapeutic role in sepsis and AKI by multiple-ingredients, multiple-targets, multiple pathways, which might be through the regulation of virus infection, inflammatory response, vascular endothelium cells and other pathways.