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中华老年病研究电子杂志 ›› 2023, Vol. 10 ›› Issue (03) : 43 -50. doi: 10.3877/cma.j.issn.2095-8757.2023.03.008

祖国传统医学

中药复方治疗男性迟发性性腺功能减退症的组方规律及分子机制
葛友涛, 蒋秋子, 卞廷松, 肖倩倩()   
  1. 225399 江苏省泰州市中医院泌尿外科
    213004 江苏省常州市中医医院男科
    271016 泰安,山东第一医科大学运动医学与康复学院;250355 济南,山东中医药大学博士后科研流动站
  • 收稿日期:2022-12-02 出版日期:2023-08-28
  • 通信作者: 肖倩倩

Study on the law of formation and molecular mechanism of traditional Chinese medicine in treating late-onset hypogonadism in male

Youtao Ge, Qiuzi Jiang, Tingsong Bian, Qianqian Xiao()   

  1. Department of Urology, Taizhou Hospital of Traditional Chinese Medicine, Taizhou 225399, China
    Department of Andrology, Changzhou Traditional Chinese Medicine Hospital, Changzhou 213004, China
    School of Sports Medicine and Rehabilitation, Shandong First Medical University, Tai'an 271016, China; Shandong University of Traditional Chinese Medicine, Jinan 250355, China
  • Received:2022-12-02 Published:2023-08-28
  • Corresponding author: Qianqian Xiao
引用本文:

葛友涛, 蒋秋子, 卞廷松, 肖倩倩. 中药复方治疗男性迟发性性腺功能减退症的组方规律及分子机制[J]. 中华老年病研究电子杂志, 2023, 10(03): 43-50.

Youtao Ge, Qiuzi Jiang, Tingsong Bian, Qianqian Xiao. Study on the law of formation and molecular mechanism of traditional Chinese medicine in treating late-onset hypogonadism in male[J]. Chinese Journal of Geriatrics Research(Electronic Edition), 2023, 10(03): 43-50.

目的

探讨中药复方治疗男性迟发性性腺功能减退症(LOH)的用药规律及其核心分子机制。

方法

检索知网、万方、维普三大中文期刊全文数据库中截至2022年8月31日已公开发表的所有中医药治疗LOH的相关文献。应用SPSS软件统计获得的中药复方核心药物;应用网络药理学方法获得核心药物主要活性成分及对药物作用靶点进行预测;应用STRING11.5在线数据库构建共有靶点蛋白互作网络(PPI),获得关键靶点;通过基因本体(GO)及京都基因与基因组百科全书(KEGG)富集分析获得核心药物的作用机制。

结果

纳入符合标准文献共138篇,收集处方177张,共涉及中药202味,其中使用频率高于1%的有31味,药性以寒、温为主,药味多为甘味,主要归肾、肝两经。聚类分析结果显示,上述高频药物可得到4个中药聚类组合,分别为二仙汤类、地黄汤类、逍遥散类和补心丹类。关联规则18条,结合用药频次及关联规则得到核心药物8种,分别为茯苓、当归、白芍、熟地黄、枸杞子、淫羊藿、山药、山茱萸。通过中药系统药理学数据库与分析平台筛选与疾病靶点取交集得到111个共有靶点,其中AKT1、TP53、JUN、EGFR、TNF、IL-6等是核心靶点。GO分析共获得涉及1 606个生物学过程,81个细胞组分,146个分子功能;KEGG共富集200个条目,主要为癌症的途径、AGE-RAGE信号通路、内分泌抵抗、脂质与动脉粥样硬化、HIF-1信号通路、PI3K-Akt信号通路、MAPK信号通路、细胞衰老等。

结论

LOH的中医治疗多从补肾疏肝立法,兼顾健脾、养血、安神,中药组方具有多成分、多通路、多靶点等优点,疗效可涉及该病发生、发展、症状改善、预防并发症的全过程。

Objective

To explore the medication patterns and core molecular mechanisms of traditional Chinese medicine in the treatment of late-onset hypogonadism in male (LOH).

Methods

Literature on the treatment of LOH with traditional Chinese medicine was searched in CNKI, Wanfang, and VIP databases up to August 31, 2022, and SPSS software was used to statistically identify the core drugs. The main active ingredients of core drugs and their targets were analyzed using network pharmacology methods. Protein-protein interaction network was constructed using STRING 11.5 online database to obtain the key targets. The mechanism of core drugs in treating LOH was obtained through Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis.

Results

A total of 138 articles were included in the study, and 177 prescriptions were collected, involving a total of 202 flavors of traditional Chinese medicine, of which 31 were used with frequency higher than 1%. The medicinal properties were mainly cold and warm, and the taste was mostly sweet, mainly attributed to the kidney and liver meridians. The above high-frequency drugs could be classified into four clusters, which were Erxian Tang, Dihuang Tang, Xiaoyao Powder, and Buxin Dan. There are 18 association rules, and 8 core drugs, namely Poria cocos, Angelica sinensis, Paeonia lactiflora, Rehmannia glutinosa, Lycium barbarum, Epimedium, Chinese yam, and Cornus officinalis. Through Traditional Chinese Medicine Systems Pharmacology screening and disease target intersection, 111 common targets were obtained, among which AKT1, TP53, JUN, EGFR, TNF, IL-6 were core targets. GO analysis revealed a total of 1606 biological processes, 81 cell components, and 146 molecular functions involved; KEGG enriches a total of 200 entries, mainly including the pathway in cancer, AGE-RAGE signaling pathway, endocrine resistance, lipid and atherosclerosis, HIF-1 signaling pathway, PI3K-Akt signaling pathway, MAPK signaling pathway, cellular senescence, etc.

Conclusion

The treatment of LOH is mainly based on tonifying the kidney and soothing the liver, while also taking into account spleen strengthening, blood nourishing, and calming the nerves, which has the advantages of multi-components, multi-pathways, and multi-targets, and the efficacy of the treatment can involve the whole process of the disease, including the occurrence and development of the disease, improvement of the symptoms, and prevention of the complications.

图1 文献筛选流程图
表1 男性迟发性性腺功能减退症中药治疗中使用频率>1%的高频药物
图2 男性迟发性性腺功能减退症中药治疗高频药物性味归经统计
图3 男性迟发性性腺功能减退症治疗高频中药聚类分析谱系图
表2 男性迟发性性腺功能减退症治疗高频中药聚类分析结果
图4 男性迟发性性腺功能减退症治疗核心药物关联分析图。图4A位关联规则网络图,图4B为互作网络关系图
表3 男性迟发性性腺功能减退症治疗用药关联规则下的核心药对(组)
表4 男性迟发性性腺功能减退症治疗中药共有成分
图5 男性迟发性性腺功能减退症治疗的"中药-活性成分-靶点-疾病"网络图注:蓝色代表白芍所含活性成分,粉色代表茯苓所含活性成分,橙色代表枸杞子所含活性成分,绿色代表山药所含活性成分,紫代表山茱萸所含活性成分,墨绿色代表淫羊藿所含活性成分,红色代表多种中药共有成分,熟地黄、当归所有活性成分包含在红色区域,内圈中天蓝色代表中药名称,黄色代表靶点
图6 男性迟发性性腺功能减退症治疗用药靶点蛋白相互作用网络分析排名前20个靶点基因
图7 男性迟发性性腺功能减退症治疗用药靶点基因本体富集分析图
图8 男性迟发性性腺功能减退症治疗用药靶点京都基因与基因组百科全书富集分析图
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