养荣润肠舒合剂治疗慢传输型便秘的作用机制

Mechanism of Yangrong Runchangshu Mixture(养荣润肠舒合剂)in Treatment of Slow Transit Constipation

目的采用网络药理学结合动物实验分析养荣润肠舒合剂治疗慢传输型便秘(slow transit constipation,STC)的作用机制。方法利用TCMSP数据库检索养荣润肠舒合剂中各药物的有效活性成分,并通过SwissTargetPredict网站进行靶点预测;在Genecards、OMIM数据库获取STC的相关靶点,药物及疾病的靶点取交集后,获得共有靶点,构建共有靶点图;通过String数据库进行PPI分析,利用Cytoscape软件进行拓扑特征分析,得到核心靶点,构建核心靶点-成分网络图;通过DAVID平台进行GO及KEGG富集分析,构建靶点-通路网络图。筛选出养荣润肠舒合剂治疗STC的可能作用靶点及通路,然后动物实验进一步验证养荣润肠舒合剂治疗STC的作用机制。结果共筛选到养荣润肠舒合剂中有效活性成分191个,作用靶点1280个。获取慢传输型便秘相关靶点990个,取交集后得到共有靶点265个。拓扑特征分析后得到核心靶点35个,核心成分157个。GO和KEGG富集分析显示养荣润肠舒合剂治疗STC可能是通过PI3K-Akt、MAPK、神经活性配体-受体相互作用等183条信号通路来治疗STC。B组大鼠结肠内5-HT、VIP表达明显高于其他各组(P<0.05),C、D、E、F组大鼠结肠内5-HT、VIP表达均有不同程度降低(P<0.05)。结论养荣润肠舒合剂可能通过作用于神经活性配体-受体相互作用、PI3K-Akt、MAPK等信号通路调节5-HT、VIP的表达水平,进而治疗STC。

Objective To analyze the mechanism of Yangrong Runchangshu Mixture(养荣润肠舒合剂)in the treatment of slow transit constipation(STC)by network pharmacology and animal experiment.Methods Firstly,the effective active components of each drug in Yangrong Runchangshu Mixture were searched through TCMSP database,and the target was predicted through SwissTargetPredict website.The relevant targets of STC were obtained in Genecards and OMIM databases,and the intersection of the targets of drugs and diseases were taken to obtain the common targets and construct the common target map.PPI analysis was carried out through string database,topological feature analysis was carried out by using Cytoscape software,the core target was obtained,and the core target component network diagram was constructed.GO and KEGG enrichment analysis was carried out through David platform,and the target pathway network diagram was constructed.The possible targets and pathways of Yangrong Runchangshu Mixture in the treatment of STC were screened,and then the mechanism of Yangrong Runchangshu Mixture in the treatment of STC was further verified by animal experiments.Results A total of 191 active components and 1280 targets were screened in Yangrong Runchangshu Mixture.A total of 990 targets related to STC were obtained,and 265 targets were obtained after taking the intersection.After topological feature analysis,35 core targets and 157 core components were obtained.GO and KEGG enrichment analysis showed that Yangrong Runchangshu Mixture may treat STC through 183 signal pathways such as phosphoinositide 3-kinase(PI3K)-protein kinase B(Akt),mitogen-activated protein kinase(MAPK)and neuroactive ligand receptor interaction.The expressions of 5-hydroxytryptamine(5-HT)and vasoactive intestinal polypeptide(VIP)in the colon of rats in group B were significantly higher than those in other groups(P<0.05).The expressions of 5-HT and VIP in the colon of rats in groups C,D,E and F decreased to varying degrees(P<0.05).Conclusion Yangrong Runchangshu Mixture may regulate the expressions of 5-HT and VIP by acting on neuroactive ligand receptor interaction,PI3K Akt,MAPK and other signal pathways,and then treat STC.