| 摘要: |
| 目的：基于网络药理学探讨清热合剂治疗脓毒症的作用机制。方法：利用TCMSP检索清热合剂组成药物的主要成分;通过疾病数据库检索与脓毒症相对应的靶点，构建药物-成分-靶点网络分析图;绘制韦恩图获得药物-疾病的交集靶点;并构建药物-疾病共同靶点的蛋白质-蛋白质相互作用（PPI）网络;运用DAVID数据库进行基因本体（GO）功能、京都基因与基因组百科全书（KEGG）通路富集分析;将所涉及的重要靶点应用CB-Dock2软件完成分子对接。构建脓毒症大鼠模型，对清热合剂治疗脓毒症的作用进行验证。结果：清热合剂主要成分为槲皮素、木犀草素、山柰酚、β-谷甾醇等，与脓毒症潜在交集靶点有信号转导和转录激活因子3（STAT3）、丝氨酸/苏氨酸激酶1（AKT1）、V-rel网状内皮细胞病毒癌基因同源物A（RELA）、丝裂原活化蛋白激酶（MAPK）、肿瘤坏死因子（TNF）、白细胞介素-6（IL-6）、白细胞介素-10（IL-10）等，GO功能与KEGG通路富集结果包括高级糖基化终末产物-受体（AGE-RAGE）通路、脂质和动脉粥样硬化、血流剪切力调控动脉粥样硬化、白细胞介素-17（IL-17）、TNF等信号通路。分子对接清热合剂主要成分与重要靶点均可实现良好对接，结合能<-7.0 kcal/mol。动物实验结果提示，随着清热合剂浓度的增加，脓毒症大鼠的存活率逐渐提高，且肿瘤坏死因子-α（TNF-α）水平逐步下降，改善促炎-抗炎失衡可能是其主要作用机制之一。结论：清热合剂可能通过调控STAT3、AKT1、RELA、MAPK、TNF、IL-6、IL-10等核心靶点及IL-17、TNF等炎症、免疫信号通路发挥治疗脓毒症的作用。 |
| 关键词: 脓毒症 清热合剂 网络药理学 炎症状态 大鼠 信号通路 |
| DOI： |
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| Mechanism of action of Qingre mixture in treatment of sepsis：A study based on network pharmacology |
| LI Yan,YUAN Jingya,YANG Xin |
| (The Second Affiliated Hospital of Tianjin University of Traditional Chinese Medicine，Tianjin 300150，China) |
| Abstract: |
| Objective：To investigate the mechanism of action of Qingre mixture in the treatment of sepsis based on network pharmacology.Methods：TCMSP database was used to obtain the active components of drugs in Qingre mixture，and disease database was used to obtain the targets associated with sepsis and establish a drug-component-target network.Venn diagram was plotted to obtain drug-disease intersecting targets，and a protein-protein interaction network was established for the common targets of drug and disease.DAVID database was used to perform the gene ontology (GO) functional enrichment analysis and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis，and CB-Dock2 was used to perform molecular docking of important targets.A rat model of sepsis was established to validate the therapeutic effect of Qingre mixture on sepsis.Results：The main components of Qingre mixture included quercetin，luteolin，kaempferol，and beta-sitosterol，and the potential intersecting targets of sepsis included STAT3，AKT1，RELA，MAPK，TNF，IL-6，and IL-10.The GO functional enrichment analysis and the KEGG pathway enrichment analysis showed the main signaling pathways of AGE-RAGE，lipid and atherosclerosis，fluid shear stress and atherosclerosis，interleukin-17，and TNF.Molecular docking showed good binding between the main components of Qingre mixture and important targets，with a binding energy of <-7.0 kcal/mol.The animal experiment showed that the survival rate of rats with sepsis gradually increased with the increase in the concentration of Qingre mixture，while the level of tumor necrosis factor-α gradually decreased，suggesting that Qingre mixture might exert a therapeutic effect by improving pro-inflammatory/anti-inflammatory balance.Conclusion：Qingre mixture may exert a therapeutic effect on sepsis by regulating the core targets such as STAT3，AKT1，RELA，MAPK，TNF，IL-6，and IL-10 and the inflammatory and immune signaling pathways such as IL-17 and TNF. |
| Key words: sepsis Qingre mixture network pharmacology inflammatory state rat signaling pathway |
