基于生物信息技术探讨济川煎治疗慢传输型便秘的机制

The Mechanism of Jichuan Jian in the Treatment of Slow Transit Constipation Based on Bioinformatics Technology

目的:通过生物信息技术探索济川煎的有效化学成分及其作用于人体的靶点基因,分析其治疗慢传输型便秘(slow transit constipation,STC)的机制。方法:通过中药系统药理学技术平台(traditional Chinese medicine systems pharmacology database and analysis platform,TCMSP)数据库检索和筛选济川煎的化学活性物质及其作用于人体的靶点蛋白,同时应用人类基因数据库(the human gene database,GeneCards)预测STC的作用靶点,构建活性成分-靶点网络图;通过String数据库平台构建蛋白-蛋白相互作用网络(protein-protein interactions,PPI),寻找PPI核心基因,再进行GO(gene ontology)富集分析和KEGG(kyoto encyclopedia of genes and genomes)富集分析,找出所涉及的信号通路,构建靶点-通路网络图。结果:济川煎治疗STC的关键化学成分共25个,与STC的共同靶点71个;GO富集包括金属离子应答、膜筏、磷酸酶结合等;KEGG富集包括卡波西氏肉瘤相关疱疹病毒感染、前列腺癌、乙型肝炎、大肠癌等;与上述通路匹配度较高的靶点基因包括丝裂原活化蛋白激酶3(mitogen-activated protein kinase 3,MAPK3)、丝裂原活化蛋白激酶1(mitogen-activated protein kinase 1,MAPK1)、RAC-α丝氨酸/苏氨酸蛋白激酶(RAC-alpha serine/threonine-protein kinase,Akt1)、BCL2-AssociatedX的蛋白质(BCL2-AssociatedX,BAX)、RAF原癌基因丝氨酸/苏氨酸-蛋白激酶(Raf-1 proto-oncogene,serine/threonine,RAF1)等。结论:济川煎可通过调节富集在卡波西氏肉瘤相关疱疹病毒感染、前列腺癌、乙型肝炎、大肠癌等通路的MAPK3、MAPK1、Akt1、BAX、RAF1等靶点对STC起治疗作用。

Objective:To explore the effective chemical ingredients of Jichuan Jian and the target genes acting on human body by bioinformatics technology,and analyze its mechanism of treating STC.Methods:Chemically reactive substance of Jichuan Jian and target proteins acting on human body were searched and screened by TCMSP,meanwhile the targets of the disease were predicted by applying Genecards to construct active component-target network diagram;PPI was established via String database,to find out the core genes of PPI,and then,GO and KEGG were carried out to survey the signaling pathway involved,and structure targetpathway network diagram.Results:There were 25 key chemical components of Jichuan Jian in treating STC,and 71 common targets;GO enrichment contained metal ion response,membrane raft,phosphatase binding and others;KEGG enrichment included Kaposi's sarcoma associated herpesvirus infection,prostatic cancer,hepatitis B and colorectal cancer,and the target genes with high matching degree with the above pathways were MAPK3,MAPK1,Akt1,BAX and RAF1.Conclusion:Jichuan Jian could develop therapeutic effects on STC through regulating the targets such as MAPK3,MAPK1,Akt1,BAX,RAF1 enriched in the pathways including Kaposi's sarcoma associated herpesvirus infection,prostatic cancer,hepatitis B and colorectal cancer.