基于网络药理学及动物实验探讨益肾通络方治疗糖尿病性勃起功能障碍的作用机制

    Mechanism of Yishen Tongluo Formula in the Treatment of Diabetes Induced Erectile Dysfunction Based on Network Pharmacology and Animal Experiments

    • 摘要:
      目的 基于网络药理学预测益肾通络方治疗糖尿病性勃起功能障碍的活性成分、作用靶点及信号通路,通过分子对接和动物实验验证其治疗糖尿病性勃起功能障碍的可能作用机制。
      方法 通过TCMSP数据库收集益肾通络方的有效成分及靶点;通过GeneCards数据库获取糖尿病性勃起功能障碍疾病靶点;通过Venny2.1软件获得交集靶点基因,结合 STRING 数据库绘制蛋白相互作用网络,并通过 Cytoscape 3.9.1 软件筛选益肾通络方治疗糖尿病性勃起功能障碍的核心作用靶点。对获取的靶点基因进行GO和KEGG富集分析;利用Dock Thor在线网站对核心靶点与对应的活性成分进行分子对接,最终借助Pymol软件进行可视化。
      结果 益肾通络方存在100个有效成分,24个治疗疾病的有效靶点,核心靶点为AKT1、IL6、CASP3、VEGFA、MAPK8、NOS3、EGF、CCND1、EDN1、CRP;GO富集分析得到254条生物学过程、24个分子功能以及14个细胞组成成分,如正向调控基因表达、正向调控细胞增殖、负向调控基因表达、正向调控凋亡过程等生物学过程,钙调蛋白结合、氧化还原酶活性、特异性序列DNA结合等分子功能,大分子复合物、蛋白结合、相同蛋白结合等细胞组成分;KEGG富集分析筛选出98条富集通路,如糖尿病并发症中的AGE-RAGE信号通路、PI3K-AKT通路、ROCK/MYPT1途径等。核心靶点与对应的活化成分分子对接良好。动物实验表明,益肾通络方能够有效改善糖尿病大鼠的勃起功能。结论 益肾通络方可通过多靶点、多通路、多途径改善糖尿病性勃起功能障碍。

       

      Abstract:
      OBJECTIVE To predict the active components, targets and signal pathways of Yishen Tongluo formula in the treatment of diabetes induced erectile dysfunction based on network pharmacology, and to verify the possible mechanism of Yishen Tongluo formula in the treatment of diabetes induced erectile dysfunction through molecular docking and animal experiments.
      METHODS The active ingredients and targets of Yishen Tongluo formula were collected from TCMSP database. The disease targets of diabetic erectile dysfunction were obtained from the GeneCards database. Venny2.1 software was used to obtain the intersection target genes, and STRING database was used to draw the protein interaction network. Cytoscape 3.9.1 software was used to screen the core targets of Yishen Tongluo formula in the treatment of diabetic erectile dysfunction. GO and KEGG enrichment analysis of the target genes were performed. The Dock Thor online website was used to perform molecular docking between the core targets and the corresponding active ingredients, and finally the visualization was performed with the help of Pymol software.
      RESULTS Yishen Tongluo formula had 100 active components and 24 effective targets for the treatment of diseases. The core targets were AKT1, IL6, CASP3, VEGFA, MAPK8, NOS3, EGF, CCND1, EDN1, and CRP. GO enrichment analysis obtained 254 biological processes, 24 molecular functions and 14 cellular components, such as positive regulation of gene expression, positive regulation of cell proliferation, negative regulation of gene expression, positive regulation of apoptosis process and other biological processes, calmodulin binding, oxidoreductase activity, specific sequence DNA binding and other molecular functions. Macromolecular complex, protein binding, same protein binding and other cell components; KEGG enrichment analysis screened out 98 enriched pathways, such as AGE-RAGE signaling pathway, PI3K-AKT pathway, ROCK/MYPT1 pathway in diabetic complications. The core targets docking well with the corresponding activated component molecules. Animal experiments shown that Yishen Tongluo formula could effectively improve the erectile function of diabetic rats.
      CONCLUSION Yishen Tongluo Formula can improve diabetic erectile dysfunction through multiple targets, pathways and pathways.

       

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