基于网络药理学探讨杜仲治疗继发性甲状旁腺功能亢进的作用机制  

Mechanisms of Eucommia Ulmoides against Secondary Hyperparathyroidism Basedon Network Pharmacology

作　　者：唐昊 文天林 杨猛[2] TANG Hao;WEN Tian-lin;YANG Meng(Dongzhimen Hospital,Beijing University of Chinese Medicine,Beijing 100700,China;China-Japan Friendship Hospital,Beijing 100029,China)

机构地区：[1]北京中医药大学东直门医院,北京100700 [2]中日友好医院,北京100029

出　　处：《解放军药学学报》2025年第1期91-98,103,共9页Pharmaceutical Journal of Chinese People's Liberation Army

基　　金：中央高水平医院临床科研业务,No.2023-NHLHCRF-YYPPLC-ZR-08。

摘　　要：目的探讨分析杜仲治疗继发性甲状旁腺功能亢进的作用机制,为杜仲的作用机制研究和新药开发提供理论支持。方法采用TCMSP数据库进行杜仲活性成分及相关靶点,通过UniProt数据库获取具体的基因靶点与GeneCards、DisGeNET和OMIM数据库中的继发性甲状旁腺功能亢进症靶点基因结合,发现关键靶点。研究通过Cytoscape和MCODE插件进行聚类分析,并用度值插件筛选核心基因。基于此,结合分子对接技术验证杜仲治疗继发性甲状旁腺功能亢进的作用靶点。最后,采用DAVID进行GO和KEGG富集分析,研究目标基因功能。结果筛选出28个活性成分和114个靶标,揭示了杜仲治疗继发性甲状旁腺功能亢进的作用机制,共涉及MAPK、mTOR、RAS、PI3K-Akt信号通路和MicroRNAS等。与EGFR、HRAS、MAPK1、PIK3CA、PTK2基因关联较大,HRAS是核心基因,山奈酚是关键活性成分。结论杜仲治疗继发性甲状旁腺功能亢进的主要机制是通过调节MAPK和mTOR信号通路,降低甲状旁腺激素分泌,进而改善甲状旁腺细胞异常增殖。Objective To explore the mechanism of Eucommia Ulmoides against secondary hyperparathyroidism in order to provide data for the development of new drugs.Methods The UniProt database was searched to obtain specific target genes,which were combined with target genes related to secondary hyperparathyroidism from the GeneCards,DisGeNET,and OMIM databases to identify key targets.Cytoscape and the MCODE plugin were used for analysis while the degree plugin was adopted to screen for core genes.Molecular docking technology was employed to verify the targets of Eucommia Ulmoides in the treatment of secondary hyperparathyroidism.DAVID was used for GO and KEGG enrichment analysis to investigate the functions of the target genes.Results A total of 28 active ingredients and 114 targets related to the treatment of secondary hyperparathyroidism with Eucommia Ulmoides were screened.Among them,MAPK,mTOR,RAS,PI3K-Akt signaling pathways,and MicroRNAs were closely associated with such genes as EGFR,HRAS,MAPK1,PIK3CA,and PTK2.HRAS was identified as the core gene,while kaempferol was the key active ingredient.Conclusion The mechanism of Eucommia Ulmoides against secondary hyperparathyroidism is chiefly by regulating MAPK and mTOR signaling pathways,reducing PTH secretion,and improving the abnormal proliferation of parathyroid cells.

关 键 词：网络药理学 分子对接 杜仲 继发性甲状旁腺功能亢进 

分 类 号：R582[医药卫生—内分泌]