基于网络药理学和生物信息学探讨健脾益气方治疗免疫性血小板减少症作用机制

Jianpi Yiqi decoction treatment of immune thrombocytopenia:a network pharmacology and bioinformatical study

目的利用网络药理学和生物信息学探讨健脾益气方治疗免疫性血小板减少症(ITP)的作用机制。方法利用中药系统药理学数据库与分析平台(TCMSP)和BATMAN-TCM数据库韦恩筛选得到健脾益气方主要活性成分,SwissTargetPrediction数据库进行靶点预测;DisGenet、GeneCards、DrugBank数据库获得ITP的相关靶基因,将药物活性成分靶点与ITP靶点韦恩,获得健脾益气作用于ITP的预测靶点。利用R语言对交集靶点进行基因功能(GO)分析和京都基因与基因组百科全书(KEGG)通路富集分析和可视化。进一步将健脾益气方治疗ITP的关键靶点与从人类自噬数据库中共获得基因进行映射,获得健脾益气方治疗ITP自噬相关靶点。结果共挖掘到健脾益气方中22种化学成分及763个潜在靶点,ITP疾病相关靶点3130个,得到健脾益气方-疾病共同靶点337个。根据MCC算法,得到TOP10基因,其中有5个主要富集在PI3K/Akt信号通路。进一步分析健脾益气方治疗ITP的自噬相关关键靶点,得到健脾益气方治疗ITP自噬相关交集靶标36个,主要富集在自噬、凋亡等通路上。最后根据靶点的计数,获得健脾益气方治疗ITP自噬相关可能的关键靶点是EGFR、PARP1、MOTR、BCL2L1、RAF1、BCL2、HDAC6等。结论健脾益气方通过调节PI3K/Akt/mTOR信号通路或自噬的关键蛋白来靶向自噬可能为ITP提供一种有前景的治疗方法。EGFR、PARP1、MOTR、BCL2L1、RAF1、BCL2、HDAC6等分子可能是健脾益气方诱导自噬,抑制血小板凋亡,治疗ITP的关键靶点。

Objective To assess the potential mechanism of Jianpi Yiqi decoction in treating immune thrombocytopenia(ITP)using a network pharmacology and bioinformatical analysis.Methods The main active ingredients in Jianpi Yiqi decoction were screened using TCM systematic pharmacology database and analysis platform(TCMSP)and BATMAN-TCM database's Wayne tools,while the targeting genes were predicted using Swiss-Target-Prediction database and ITP-related gene targets were identified using DisGenet,GeneCards and DrugBank databases.The drug active ingredients-targeting genes and IPT-altered gene Wayne were analyzed to obtain the predicted targets in strengthening the spleen and nourishing the qi on ITP.The gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis and visualization were performed to analyze their targeting genes using the R software.After that,the key targeting genes of Jianpi Yiqi decoction in ITP treatment were mapped with genes obtained from human autophagy database to obtain autophagy-related target genes of Jianpi Yiqi decoction in treating ITP.Results There were 22 chemical components and 763 potential targets identified in Jianpi Yiqi decoction,while there were 3130 ITP-related target genes,leading to 337 genes in both Jianpi Yiqi decoction and ITP.The top 10 genes were identified and five of them were mainly concentrated in the PI3K/Akt signaling.Further analysis of the key target genes related to autophagy in Jianpi Yiqi decoction treatment of ITP revealed 36 intersecting target genes related to autophagy in ITP treatment,which were mainly concentrated in cell autophagy and apoptosis.According to the target gene count,the potential key target genes of Jianpi Yiqi decoction in treatment of ITP autophagy were EGFR,PARP1,MOTR,BCL2L1,RAF1,BCL2,and HDAC6.Conclusion Jianpi Yiqi decoction in ITP treatment was to regulate the PI3K/Akt/mTOR signal pathway and the key autophagy proteins,especially targeting of EGFR,PARP1,MTOR,BCL2L1,RAF1,BCL2,HDAC6 and other molecules in induction of platelet autophagy but inhibition of apoptosis in ITP treatment.