基于生物信息数据探究肾阴虚证病理机制

Analysis of Pathological Mechanism of Kidney-Yin Deficiency Syndrome Based on Biological Information Data

目的:利用生物信息学对异病同证肾阴虚证靶点进行筛选与分析,探讨肾阴虚证病理机制。方法:从SymMap和HSDN数据库得到肾阴虚证中医症状靶点。DisGeNET、GeneCards、TTD、Drugbank数据库得到骨质疏松、2型糖尿病、原发性高血压的疾病靶点,将3种疾病靶点分别与肾阴虚证症状靶点取交集,获得3类疾病-症状靶点。从TCMSP、ETCM、TCMID和BATMAN-TCM数据库检索六味地黄丸的有效成分,STITCH、Swiss Target Prediction、TCMSP数据库预测药物靶点。将3类疾病-症状靶点和六味地黄丸药物靶点分别导入PINA平台进行蛋白互作分析,通过对3类疾病-症状蛋白互作靶点取交集,获得肾阴虚病证结合靶点;通过对药物靶点与肾阴虚病证结合靶点取交集,获得方证结合靶点。然后分别对肾阴虚病证结合靶点和方证结合靶点分别进行关键模块分析,并对每一模块进行富集分析,最后对六味地黄丸成分进行文献挖掘,通过“以方测证”对肾阴虚证病理机制进行验证。结果:共获得病证结合靶点1061个,方证结合靶点882个,方证结合靶点占病证结合靶点的83.1%。方证结合靶点的模块分析获得的10个模块,均与病证结合靶点的模块分析获得的11个模块相同。方证结合靶点KEGG通路富集分析,共筛选出45条通路,主要聚焦于免疫功能相关(33.3%,15/45),癌症(17.8%,8/45)、传染性疾病(13.3%,6/45)、遗传信息处理(13.3%,6/45)等。文献挖掘发现六味地黄丸中共有34(14.1%)种成分已被证实具有调节多种免疫细胞及免疫因子的作用。结论:肾阴虚证病理机制主要涉及机体免疫功能紊乱,还可能包括遗传信息传递过程异常。

Objective:To screen and analyze the target of kidney-yin deficiency syndrome,and explore the pathological mechanism of kidney-yin deficiency syndrome by using bioinformatics.Methods:The TCM symptom targets of kidney-yin deficiency syndrome were obtained from SymMap and HSDN database.DisGeNET,GeneCards,TTD and Drugbank obtained the target of osteoporosis,type 2 diabetes and essential hypertension.The 3 disease targets were collected from the kidney-yin deficiency syndrome targets respectively,and 3 categories of disease-symptom targets were obtained.The effective components of Liuwei Dihuang Pill were retrieved fromTCMSP,ETCM,TCMID and BATMAN-TCM databases,and the drug targets were predicted from STITCH,Swiss Target Prediction and TCMSP databases.Then the three kinds of disease symptom targets and Liuwei Dihuang Pill drug targets were introduced into PINA platform for protein interaction analysis.By taking the intersection of the three kinds of disease symptom protein interaction targets,the binding targets of kidney-yin deficiency syndrome were obtained.Through the intersection of drug target and kidney-yin deficiency syndrome combination target,the prescription syndrome combination target is obtained.Then,the first mock exam was carried out on the target of kidney-yin deficiency syndrome,combined with the target and the combination of target and syndrome,and each module was analyzed.Finally,the ingredients of Liuwei Dihuang Pill were excavated and the pathological mechanism of kidney-yin deficiency was verified by"determining the syndrome with classical prescriptions".Results:A total of 1061 disease syndrome binding targets and 882 prescription syndrome binding targets were obtained,accounting for 83.1%of the disease syndrome binding targets.The 10 modules obtained from the module analysis of prescription syndrome combined with target are the same as the 11 modules obtained from the module analysis of disease syndrome combined with target.Based on the enrichment analysis of the target KEGG pathway,45 pathways were screened,mainly focusing on immune function related(33.3%,15/45),cancer(17.8%,8/45),infectious diseases(13.3%,6/45),genetic information processing(13.3%,6/45),etc.Literature mining found that there are 34(14.1%)components in Liuwei Dihuang Pill,which have been proved to regulate a variety of immune cells and immune factors.Conclusion:The pathological mechanism of kidney-yin deficiency syndrome mainly involves the disorder of immune function,and may also include the abnormality of genetic information transmission process.