基于网络药理学的墨旱莲-女贞子药对“异病同治”糖尿病肾病与糖尿病视网膜病变的机制研究  

Treating different disease with same method in traditional Chinese medicine:mechanisms of Eclipta alba-glossy privet fruit medicinal pair in treating diabetic nephropathy and diabetic retinopathy based on network pharmacology

作　　者：王娟 韩旭 李立[1] 韩森 赵宁[1] 崔赵丽[3] 丁治国[4] 王光磊[5] 姜淼[1] 顾浩[1] WANG Juan;HAN Xu;LI Li;HAN Sen;ZHAO Ning;CUI Zhaoli;DING Zhiguo;WANG Guanglei;JIANG Miao;GU Hao(Institute of Basic Research in Clinical Medicine,China Academy of Chinese Medical Sciences,Beijing 100700,China;Department of Science and Education,Weifang Traditional Chinese Medicine Hospital,Weifang 262699,China;Department of Endocrinology,East District of Dongzhimen Hospital,Beijing University of Chinese Medicine,Beijing 101100,China;Department of Surgery,East District of Dongzhimen Hospital,Beijing University of Chinese Medicine,Beijing 101100,China;Physical Examination Center,Dongzhimen Hospital,Beijing University of Chinese Medicine,Beijing 100700,China)

机构地区：[1]中国中医科学院中医临床基础医学研究所,北京100700 [2]潍坊市中医院科教部,潍坊262699 [3]北京中医药大学东直门医院东区内分泌科,北京101100 [4]北京中医药大学东直门医院东区外科,北京101100 [5]北京中医药大学东直门医院体检中心,北京100700

出　　处：《天津中医药大学学报》2021年第3期374-383,共10页Journal of Tianjin University of Traditional Chinese Medicine

基　　金：国家自然科学基金面上项目(81873181,81473367);国家自然科学基金青年基金项目(81603401);中央级公益性科研院所基本科研业务费专项资金资助项目(Z0659,Z0647);北京市科技计划课题资助项目(Z121100000312006)。

摘　　要：[目的]通过网络药理学的方法,研究墨旱莲-女贞子药对“异病同治”糖尿病肾病(DN)与糖尿病视网膜病变(DR)的药理作用机制,验证国医大师吕仁和教授治疗DN与DR的临床经验。[方法]利用TCMSP、TCMID和Uniprot数据库,搜集并获取墨旱莲、女贞子的化学成分及其作用靶点。利用NCBI-gene、Genecards和OMIM数据库搜集DN和DR的疾病相关靶点。通过String数据库、Cytoscape3.7.2软件、TBtools软件构建药物靶点蛋白相互作用网络,获取交集靶点。利用BioGPS数据库和Cytoscape3.7.2软件构建作用靶点-组织分布网络图,运用GO数据库和Cytoscape3.7.2软件的ClueGO插件对交集靶点进行GO和KEGG富集分析。[结果]墨旱莲-女贞子药对主要含有14个活性成分和124个潜在作用靶点,DN相关靶点2614个,DR相关靶点2587个,其中药对同时作用于DN和DR的共同靶点有63个。有11个作用靶点在胰岛、视网膜和肾脏高表达,KEGG富集分析得到共同靶点主要富集在糖尿病并发症中的AGE-RAGE信号通路、TNF信号通路和IL-17信号通路等115条通路上,涉及对含氧化合物的反应、细胞对化学刺激的反应、对脂质的反应和细胞群增殖的调节等1686个生物过程。[结论]墨旱莲-女贞子药对可能通过调节多个靶点、多条通路和多个生物反应过程,达到对DN与DR的“异病同治”作用,为吕仁和教授的临床经验用药提供了网络药理学验证,也为今后进一步研究墨旱莲-女贞子药对的药理作用机制提供了依据。[Objective]The study aims to explore the pharmacological mechanisms of treating different disease with same method of Eclipta alba-glossy privet fruit medicinal pair in treating diabetic nephropathy(DN)and diabetic retinopathy(DR)through network pharmacology,which could validate the clinical experience of national medical master Professor LYU Renhe.[Methods]After excavating all the chemical components and medicine targets related to the Eclipta alba-glossy privet fruit medicinal pair from TCMSP,TCMID and Uniprot database,the targets of diabetic nephropathy and diabetic retinopathy were screened out through NCBI-geng,Genecards and OMIM database.Protein-protein interaction network of medicinal pair was constructed through String platform,Cytoscape software(3.7.2 version)and TBtools software;and common targets were obtained.BioGPS database and Cytoscape software were used to constructed targets-tissues network.GO database and ClueGO program in Cytoscape software were used to perform GO function enrichment analysis and KEGG pathway enrichment analysis on common targets.[Results]Totally 14 active ingredients and 124 potential targets of Eclipta alba-glossy privet fruit medicinal pair were screened out,the 2614 and 2587 targets were related to diabetic nephropathy and diabetic retinopathy;respectively,the 63 targets were related to treating both diabetic nephropathy and diabetic retinopathy in Eclipta alba-glossy privet fruit medicinal pair.The results of network analysis indicated that 11 targets were expressed highly in pancreatic islet,retina and kidney;the 115 pathways were regulated in treating DN and DR,including AGE-RAGE signaling pathway in diabetic complications,TNF signaling pathway,IL-17 signaling pathway,PI3K-Akt signaling pathway and HIF-1 signaling pathway;furthermore,1686 biological response processes were enriched as well,such as oxidative stress,inflammation,and metabolism of glucose and lipid.[Conclusion]Eclipta alba-glossy privet fruit medicinal pair may regulate multiple targets,pathways and biologi

关 键 词：墨旱莲 女贞子 糖尿病肾病 糖尿病视网膜病变 异病同治 

分 类 号：R587.2[医药卫生—内分泌]