Background

Tacrolimus is a powerful immunosuppressant and has been widely used in organ transplantation. In order to further explore the role of tacrolimus in liver transplantation, we conducted network pharmacology analysis.

Methods

GSE100155 was obtained from the GEO database, and the DEGs of liver transplantation were analyzed. The 2D structure of tacrolimus was obtained from the National Library of Medicine, and the pharmacophore model of tacrolimus was predicted using the online tool pharmmapper. Then a network of tacrolimus and target genes was constructed through network pharmacology, and visualization and GO enrichment analysis was performed through Cytoscape. In addition, we also analyzed the correlation between key genes and immune infiltrating cells. The data of GSE84908 was used to verify the changes of key gene expression levels after tacrolimus treatment.

Results

The results of network pharmacological analysis showed that tacrolimus had 43 target genes, and the GO enrichment results showed many potential functions. Further analysis found that there were 5 key target genes in DEGs, and these 5 genes were significantly down-regulated in liver transplant patients. Another important finding was that 5 genes were significantly related to some immune infiltrating cells. The results of the GSE84908 data analysis showed that after tacrolimus treatment, the expression of DAAM1 was significantly increased (p = 0.015).

Conclusion

Tacrolimus may inhibit the human immune response by affecting the expression of DAAM1 in liver transplant patients.

中文翻译：

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基于网络药理学分析他克莫司在肝移植中的作用

背景

他克莫司是一种强大的免疫抑制剂，已广泛用于器官移植。为了进一步探讨他克莫司在肝移植中的作用，我们进行了网络药理学分析。

方法

GSE100155取自GEO数据库，对肝移植的DEGs进行分析。他克莫司的二维结构来源于美国国家医学图书馆，利用在线工具pharmmapper预测他克莫司的药效团模型。然后通过网络药理学构建他克莫司和靶基因的网络，并通过Cytoscape进行可视化和GO富集分析。此外，我们还分析了关键基因与免疫浸润细胞的相关性。GSE84908数据用于验证他克莫司治疗后关键基因表达水平的变化。

结果

网络药理分析结果表明，他克莫司有43个靶基因，GO富集结果显示出许多潜在功能。进一步分析发现，DEGs中有5个关键靶基因，这5个基因在肝移植患者中显着下调。另一个重要发现是5个基因与一些免疫浸润细胞显着相关。GSE84908数据分析结果显示，经过他克莫司处理后，DAAM1的表达明显升高（p  =0.015）。

结论

他克莫司可能通过影响肝移植患者中DAAM1的表达来抑制人体免疫反应。