[关键词]
[摘要]
目的 采用数据挖掘、网络药理学和分子对接探讨国家专利中药复方治疗小儿遗尿症的用药规律及作用机制。方法 收集国家知识产权局专利查询系统和中国学术期刊全文数据库(CNKI)专利数据库中建库至2025年11月治疗小儿遗尿症的中药复方专利数据,使用Excel、IBM SPSS Modeler 18.0、IBM SPSS Statistics 20.0软件对中药复方专利进行中药频次、性味、归经和功效统计,并进行关联规则分析、聚类分析,归纳国家专利中药复方治疗小儿遗尿症的用药规律,并获取核心药物组合。同时运用网络药理学技术探讨数据挖掘筛选出的核心药物组合治疗小儿遗尿症的活性成分及其作用靶点,并采用分子对接技术加以验证。结果 最终共筛选出中药复方治疗小儿遗尿症的专利174项,涉及中药210种,累计总频次1 909次,用药频率排名前5位的中药为益智仁、桑螵蛸、菟丝子、山药、五味子,药性以甘、温为主,主归肾、脾经,常用补虚药、收涩药,关联规则分析共15组,其中支持度最高的药物组合是桑螵蛸→益智仁,高频药物聚类分析结果得到6类组合,并筛选出核心药物组合为益智仁-菟丝子-五味子。网络药理学分析结果显示该药物组合含异鼠李素、山柰酚、槲皮素、五味子酯乙、五味子素C等多种活性成分,这些成分通过作用于非受体酪氨酸蛋白激酶(SRC)、丝氨酸和苏氨酸激酶1(AKT1)、雌激素受体1(ESR1)、肿瘤坏死因子(TNF)、表皮生长因子受体(EGFR)等关键靶点,协同调控缺氧诱导因子-1(HIF-1)、人表皮生长因子受体(ErbB)等通路,体现了中药复方“多成分-多靶点”的整体作用特点;分子对接证实关键靶点与核心成分具有良好的结合能力。结论 国家专利中药复方治疗小儿遗尿症以温补下元、固摄膀胱为治则,其药物组合益智仁-菟丝子-五味子的异鼠李素、山柰酚、槲皮素等成分可通过作用于SRC、AKT1、ESR1、TNF、EGFR等多靶点,调控HIF-1、ErbB等信号通路,起到治疗小儿遗尿症的作用。
[Key word]
[Abstract]
Objective Data mining, network pharmacology and molecular docking were used to explore the medication rules and mechanism of national patented Chinese herbal compound in the treatment of nocturnal enuresis. Methods The patent data of traditional Chinese medicine compound for the treatment of nocturnal enuresis from the establishment of the patent query system of the State Intellectual Property Office and the patent database of China National Knowledge Infrastructure (CNKI ) to November 2025 were collected. Excel, IBM SPSS Modeler 18.0 and IBM SPSS Statistics 20.0 software were used to calculate the frequency, taste, meridian tropism and efficacy of traditional Chinese medicine formula, and association rule analysis and cluster analysis were carried out to summarize the medication rules of traditional Chinese medicine compound for the treatment of nocturnal enuresis and obtain the core drug combination. At the same time, network pharmacology technology was used to explore the active components and targets of the core drug combinations screened by data mining in the treatment of nocturnal enuresis, and molecular docking technology was used to verify them. Results Finally, a total of 174 patents for the treatment of nocturnal enuresis with traditional Chinese medicine were screened out, involving 210 kinds of traditional Chinese medicines, with a total cumulative frequency of 1 909 times. The top five traditional Chinese medicines with the highest frequency of medication were Alpinae Oxyphyllae Fructus, Mantidis Ootheca, Cuscutae Semen, Dioscoreae Rhizoma and Schisandrae Chinensis Fructus. The medicinal properties were mainly sweet and warm, mainly belonging to the kidney and spleen meridians. There were 15 groups of commonly used tonic and astringent drugs. The drug combination with the highest degree of support was Mantidis Ootheca→Alpinae Oxyphyllae Fructus. The results of high-frequency drug cluster analysis showed that there were six types of combinations, and the core drug combination was Alpinae Oxyphyllae Fructus-Cuscutae Semen-Schisandrae Fructus. The results of network pharmacology analysis showed that the drug combination contained many active components such as isorhamnetin, kaempferol, quercetin, schisantherin B and schisandrin C. These components synergistically regulated HIF-1, ErbB and other pathways by acting on key targets such as SRC, AKT1, ESR1, TNF and EGFR, which reflected the overall action characteristics of “multi-component-multi-target” of traditional Chinese medicine compound. Molecular docking confirmed that the key targets had good binding ability with the core components. Conclusion The national patented Chinese herbal compound in the treatment of nocturnal enuresis is based on the principle of warming and tonifying the lower yuan and consolidating the bladder. Its drug combination Alpinae Oxyphyllae Fructus-Cuscutae Semen-Schisandrae Chinensis Fructus’s isorhamnetin, kaempferol, quercetin and other components can act on SRC, AKT1, ESR1, TNF, EGFR and other targets, regulate HIF- 1, ErbB and other signaling pathways, and play a role in the treatment of nocturnal enuresis.
[中图分类号]
R965
[基金项目]
中央高水平中医医院临床科研业务费资助(00372026210601);国家自然科学基金青年科学基金项目(81403431)