滋肾降糖丸治疗糖尿病骨质疏松的作用机制探索  

Study on the mechanism of Zishen Jiangtang Pill in the treatment of diabetic osteoporosis

作　　者：连李荣 楚淑芳[2] 梁家畅 李惠林[2] 赵恒侠[2] 董彦敏[2] LIAN Lirong;CHU Shufang;LIANG Jiachang;LI Huilin;ZHAO Hengxia;DONG Yanmin(The Forth Clinical Medicine College of Guangzhou University of Chinese Medicine, Guangzhou 510000, China;Shenzhen Traditional Chinese Medicine Hospital, Shenzhen 18000, China;The Third Clinical Medicine College of Guangzhou University of Chinese Medicine, Guangzhou 510000, China)

机构地区：[1]广州中医药大学第四临床医学院,广东广州510000 [2]深圳市中医院,广东深圳518000 [3]广州中医药大学第三临床医学院,广东广州510000

出　　处：《中国骨质疏松杂志》2022年第4期551-557,共7页Chinese Journal of Osteoporosis

基　　金：广东省基础与应用基础研究基金项目(2019A1515110108);李惠林广东省名老中医药专家传承工作室(2017);陕西中医药大学张学文国医大师中医传承内分泌工作团队(SZSM201512043)。

摘　　要：目的通过网络药理学及分子对接的方法探讨滋肾降糖丸治疗糖尿病骨质疏松的作用机制。方法首先分别在TCMSP及BATMAN-TCM数据库中检索滋肾降糖丸(Zishen Jiangtang Pill,ZJP)的活性成分及作用靶点,GeneCards和OMIM数据库中检索DOP的相关靶点,并利用Venny系统获取ZJP作用于DOP的靶点;然后通过String数据库制作蛋白互作网络,运用Cytoscape软件构建“有效成分-靶点”网络图并利用插件CytoNCA获取网络核心靶点;再通过DAVID数据库对靶点进行GO功能及KEGG富集分析;最后通过PubChem数据库、PDB数据库、ChemOffice软件,进行分子对接,分析结合活性。结果ZJP中主要活性成分236个,关键活性成分5个,ZJP作用于DOP的靶点151个,核心靶点16个,GO富集条目66条,KEGG通路富集条目104条,分子对接良好。结论ZJP可能作用于TNF、IL-6、VEGF、mTOR、ESR1、PPARG等靶点,通过糖尿病并发症AGE-RAGE信号通路、TNF信号通路、流体剪切应力与动脉粥样硬化信号通路、Wnt/β-catenin、RANKL/RANK等信号通路促进成骨细胞增殖分化和破骨细胞凋亡、抑制破骨细胞的生成,从而达到治疗DOP的作用。Objective To explore the mechanism of ZJP in the treatment of diabetic osteoporosis by means of network pharmacology and molecular docking.Methods Firstly,the active components and targets of ZJP were retrieved from TCMSP and BATMAN-TCM databases respectively,the related targets of DOP were retrieved from GeneCards and OMIM databases,and the DOP targets of ZJP were obtained by Venny system.Then,the protein interaction network was constructed by String database.Cytoscape software was used to obtain the"active component-target"network diagram,and the CxtoNCA was used to obtain the key targets of the network.Next,GO function and KEGG enrichment analysis of genes were performed by DAVID database.Finally,PubChem database,PDB database and ChemOffice software,molecular docking was performed to analyze the binding activity.Results There were 236 main active components,5 key active components,151 DOP targets of ZJP,16 core targets,66 GO enrichment items,104 KEGG pathway enrichment items in ZIP,and good molecular docking.Conclusion The active compounds Quercetin,kaempferol,luteolin andβ-sitosterol in ZJP may act on involving targets could regulate Fluid shear stress and atherosclerosis,TNF signaling pathway,AGE-RAGE signaling pathway in diabetic complications,Wnt/β-catenin and RANKL/RANK signaling pathway to promote the proliferation and differentiation of osteoblasts,promote apoptosis of osteoclasts,inhibit the generation of osteoclasts for achieving the effect of DOP treatment.

关 键 词：网络药理学 分子对接 滋肾降糖丸 糖尿病骨质疏松 作用机制 

分 类 号：R965[医药卫生—药理学]