基于网络药理学探讨四至丸治疗绝经后骨质疏松的作用机制  

Exploration of the mechanism of Sizhi Pill in the treatment of postmenopausal osteoporosis based on network pharmacology

作　　者：魏蜀君 付康华 何青蔓 张青[1] 刘佳[1] 吴纯洁[1] 高永翔[1] WEI Shu-jun;FU Kang-hua;HE Qing-man;ZHANG Qing;LIU Jia;WU Chun-jie;GAO Yong-xiang(Chengdu University of Traditional Chinese Medicine,Chengdu 610075,Sichuan)

机构地区：[1]成都中医药大学,四川成都610075

出　　处：《中药与临床》2020年第4期15-20,共6页Pharmacy and Clinics of Chinese Materia Medica

摘　　要：目的:探索四至丸防治绝经后骨质疏松的关键靶点及药物作用机制。方法:通过检索GeneCards、OMIM、DisGeNET、Phenopedia等疾病数据库,确定绝经后骨质疏松相关的靶点,然后通过TCMSP数据库筛选出四至丸中活性化学成分和对应靶点,并通过R语言筛选出药物与疾病的共同靶点,构建"药物-候选化合物-靶点-疾病"网络图。使用STRING数据库和Cytoscape软件,构建PPI网络,使用R语言对四至丸治疗绝经后骨质疏松的关键靶点进行GO和KEGG富集分析,确定四至丸治疗本病的核心靶点和作用机制。结果:四至丸的有效化学成分共42个,基因靶点199个,疾病靶点1070个,共同靶点114个,预测JUN、AKT1、IL6、MAPK1、RELA、MAPK14等蛋白可能是四至丸防治绝经后骨质疏松的关键靶点。GO富集分析确定了2244个条目,四至丸可能通过抑制氧化应激反应、调控炎症因子、增强营养、类固醇激素样作用防治绝经后骨质疏松。KEGG通路富集分析明确了150条信号通路,其中信号通路涉及糖尿病并发症中的AGE-RAGE信号通路、动脉粥样硬化信号通路、PI3K-Akt信号通路、卡波西肉瘤相关疱疹病毒感染通路、乙型肝炎信号通路等。结论:四至丸组方配伍严谨科学,通过干预相关疾病途径,调控代谢相关通路、调节雌激素水平等方式防治绝经后骨质疏松,为四至丸作用机制的阐述提供新的思路和线索。Objective:To explore the key targets and drug action mechanism of Sizhi Pill in preventing and treating postmenopausal osteoporosis.Method:By searching GeneCards,OMIM,DisGeNET,Phenopedia and other disease databases,the targets related to postmenopausal osteoporosis were selected,and then the active chemical components and corresponding targets in Sizhi Pill were screened through the TCMSP database,and the drugs were screened through R language with the common target of the disease to construct a"drug-candidate compound-target-disease"network diagram.STRING database and Cytoscape software were applied to construct PPI network,and R language was used to perform GO and KEGG enrichment analysis on the key targets of Sizhi Pill in the treatment of postmenopausal osteoporosis,and investigate the core targets and mechanism of action of Sizhi Pill in the treatment of this disease.Result:There were 42 effective chemical components in Sizhi Pill,199 gene targets,1070 disease targets,and 114 common targets.It was predicted that JUN,AKT1,IL6,MAPK1,RELA,and MAPK14 may be account for the prevention and treatment of osteoporosis of postmenopausal women by Sizhi Pill.GO enrichment analysis identified 2244 items.Sizhi Pill may play a role in inhibiting oxidative stress,regulating inflammatory factors,enhancing nutrition,and have steroid hormone-like effects in preventing and treating osteoporosis after menopause.KEGG pathway enrichment analysis identified 150 signal pathways involving AGE-RAGE signal pathway in diabetic complication,atherosclerosis signal pathway,PI3K-Akt signal pathway,Kaposi’s sarcoma-associated herpes virus infection pathway,and Hepatitis Bsignal pathway etc.Conclusion:Sizhi Pill formula has a rigorous and scientific compatibility.It prevents postmenopausal osteoporosis by intervening in related disease pathways,regulating metabolic pathways,and regulating estrogen levels.It provides new ideas and clues for the elaboration of the mechanism of Sizhi Pill.

关 键 词：网络药理学 四至丸 骨质疏松 作用机制 

分 类 号：R285[医药卫生—中药学]