| 摘要: |
| 目的：基于网络药理学探讨肾复舒颗粒治疗慢性肾衰竭的相关靶点及其作用机制。方法：采用多个数据库获取肾复舒颗粒的化学成分、活性成分靶点及慢性肾衰竭的疾病靶点，获取药物-疾病的共同靶点，构建药物靶点-疾病靶点的蛋白质-蛋白质相互作用（PPI）网络以及核心靶点；对潜在作用靶点进行基因本体（GO）功能、京都基因与基因组百科全书（KEGG）通路富集分析；蛋白质免疫印迹实验检测5/6肾切除模型大鼠肾脏组织中磷酸化信号转录活化因子3（p-stat3）/信号转录活化因子3（stat3）以及抑癌基因（p53）蛋白的表达。结果：肾复舒颗粒共含有122个潜在活性成分，其对应872个药物靶点；共获得慢性肾衰竭的疾病靶点1159个；二者取交集后获得药物-疾病共同靶点137个。拓扑分析结果显示非受体酪氨酸激酶（SRC）、信号传导和转录激活因子3（STAT3）、p53、磷脂酰肌醇-4，5-二磷酸肌醇-3-激酶（PIK3CA）、丝裂原活化蛋白激酶1（MAPK1）等蛋白为核心靶点。GO功能富集分析结果显示肾复舒颗粒的作用靶点与基因表达的正向调控、MAPK激酶活性的正向调控、负调节凋亡过程有关。KEGG通路富集分析结果显示肾复舒颗粒的作用靶点与糖尿病并发症的晚期糖基化终产物及其受体（AGE-RAGE）信号通路、低氧诱导因子-1（HIF-1）信号通路、流体剪切应力和MAPK信号通路有关。动物实验结果表明肾复舒颗粒可抑制p-stat3/stat3以及p53的表达。结论：肾复舒颗粒可通过多成分、多靶点和多通路治疗慢性肾衰竭。 |
| 关键词: 肾复舒颗粒 慢性肾衰竭 网络药理学 |
| DOI： |
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| Mechanism of action of Shenfushu granules in treatment of chronic renal failure: A study based on network pharmacology |
| ZHAO Xi,XIANG Dong,JIANG Yunsheng |
| (Department of Pharmacy，The Second Xiangya Hospital of Central South University，Changsha 410011，Hunan，China;Harbin University of Commerce，Harbin 150006，Heilongjiang，China;Department of Nephrology，The Second Xiangya Hospital of Central South University，Changsha 410011，Hunan，China) |
| Abstract: |
| Objective: To investigate the targets and mechanism of action of Shenfushu granules in the treatment of chronic renal failure based on network pharmacology.Methods: Multiple databases were used to obtain the chemical components of Shenfushu granules，the targets of active components，and the disease targets of chronic renal failure，and the common targets of the drug and the disease were obtained.A protein-protein interaction network was constructed for the drug-disease targets，and the core targets were obtained.Gene ontology (GO) functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed for potential action targets.Western blotting was used to measure the protein expression levels of signal transducer and activator of transcription 3 (STAT3)，phosphorylated STAT3 (p-STAT3)，and the tumor suppressor gene p53 in renal tissue of 5/6 nephrectomized rats.Results: A total of 122 potential active components were obtained for Shenfushu granules，which corresponded to 872 drug targets，and 1159 disease targets were obtained for chronic renal failure，resulting in 137 common targets of the drug and the disease.The topology analysis showed that the core targets included the non-receptor tyrosine kinase SRC，STAT3，p53，phosphatidylinositol-4，PIK3CA，and mitogen-activated protein kinase 1.GO functional enrichment analysis showed that the action targets of Shenfushu granules were associated with the positive regulation of gene expression，the positive regulation of MAPK kinase activity，and the negative regulation of apoptosis，and KEGG pathway enrichment analysis showed that the action targets of Shenfushu granules were associated with the AGE-RAGE signaling pathway，the HIF-1 signaling pathway，fluid shear stress，and the MAPK signaling pathway.Animal experiments showed that Shenfushu granules inhibited the expression of STAT3，p-STAT3，and p53.Conclusion: Shenfushu granules exert a therapeutic effect on chronic renal failure via multiple components，targets，and pathways. |
| Key words: Shenfushu granules chronic renal failure network pharmacology |
