基于数据挖掘和网络药理学探究中医药治疗卵巢储备功能下降组方规律及作用机制

崔树娜; 林飞; 朱悦; 金雪宁; 黄丹; 陈婷婷; 杨晗; 李士华

doi:10.14148/j.issn.1672-0482.2023.0753

基于数据挖掘和网络药理学探究中医药治疗卵巢储备功能下降组方规律及作用机制

doi: 10.14148/j.issn.1672-0482.2023.0753

崔树娜^{1, 2, ,},
林飞¹,
朱悦¹,
金雪宁¹,
黄丹¹,
陈婷婷¹,
杨晗¹,
李士华²

1.
扬州大学医学院中西医结合学系, 江苏扬州 225001
2.
扬州大学附属医院, 江苏扬州 225009

基金项目:

江苏省中医药科技发展专项 2021ZX21

江苏省研究生培养创新工程项目 SJCX22_1833

江苏省研究生培养创新工程项目 SJCX21_1659

江苏省大学生创新创业训练计划项目 202011117115Y

详细信息

通讯作者:
崔树娜, 女, 教授, 主要从事中西医结合妇产科研究, E-mail: sncui@yzu.edu.cn

中图分类号: R285.5
计量
- 文章访问数: 200
- HTML全文浏览量: 28
- PDF下载量: 30
- 被引次数: 0
出版历程
- 收稿日期: 2022-07-11
- 网络出版日期: 2023-08-17
- 发布日期: 2023-08-10

Medication Rule and Molecular Mechanism of Chinese Medicine in the Treatment of Diminished Ovarian Reserve Based on Data Mining and Network Pharmacology

1.
Department of Integrated Chinese and Western Medicine, Medical College of Yangzhou University, Yangzhou 225001, China
2.
Affiliated Hospital of Yangzhou University, Yangzhou 225009, China

摘要

摘要: 目的基于数据挖掘技术和网络药理学方法探索中医药治疗卵巢储备功能下降(DOR)的用药规律, 总结疾病特点和用药思路, 揭示临床常用药物的物质基础和作用机制。方法从中国知网(CNKI)中收集中医药治疗卵巢储备功能下降相关临床文献, 提取方药信息, 建立用药数据库, 对证型分布、用药规律进行分析。运用网络药理学方法阐明具有补肾滋阴养血功效的高频药物组合治疗肝肾阴虚型卵巢储备功能下降的关键靶点和分子机制。结果数据库筛选得到64首方剂, 120味中药, 得到治疗卵巢储备功能下降常用的强关联性药物组合熟地、当归、白芍、菟丝子、枸杞子、淫羊藿。6味高频药物组合含有活性成分40个, 治疗肝肾阴虚型卵巢储备功能下降靶点共163个, 涉及PGR、ESR1、VEGFA等。关键信号通路主要包括癌症通路、细胞因子及其受体的相互作用、孕激素介导的卵母细胞成熟等。结论初步解析了中医治疗DOR谨守“肾虚”本质, 用药以补肾滋阴为主, 兼以理气、化瘀、健脾、疏肝为辅的配伍规律。并在分子水平揭示了具有补肾滋阴养血功效的高频药物组合治疗肝肾阴虚型DOR的机制。为后续治疗DOR药物开发和临床应用提供理论基础。
- 中药 /
- 卵巢储备功能下降 /
- 数据挖掘 /
- 网络药理学 /
- 机制
Abstract: OBJECTIVE To explore the medication patterns of traditional Chinese medicine in treating diminished ovarian reserve (DOR), summarize the characteristics of the disease and medication ideas, and reveal the material basis and mechanism of action of commonly used medicines in clinical practice by data mining technology and network pharmacology approach. METHODS Collect clinical literature related to the treatment of DOR from China National Knowledge Infrastructure (CNKI). Extract prescription information, establish a medication database, and analyze the distribution of syndrome types and medication patterns. Use network pharmacology methods to elucidate the key targets and molecular mechanisms of high-frequency medicine combinations with the effects of tonifying the kidney and nourishing Yin and blood in the treatment of DOR with liver and kidney Yin deficiency syndrome. RESULTS 64 prescriptions and 120 traditional Chinese medicines were screened from the database. The commonly used and strongly correlated medicines for DOR treatment were Cuscuta chinensis, Rehmanniae Radix Praeparata, Angelica, Radix Paeoniae Alba, Epimedium brevicornu Maxim, Fructus Lycii. The combination of six high-frequency medicines contains 40 active components and 163 targets for treating DOR with liver and kidney Yin deficiency syndrome, involving PGR, ESR1, VEGFA, etc. The key signaling pathways mainly include cancer pathways, interactions between cytokines and their receptors, progestogen-mediated oocyte maturation, etc. CONCLUSION This paper preliminarily analyzed the compatibility law of traditional Chinese medicine in treating DOR, adhering to the essence of "kidney deficiency", with nourishing liver and kidney essence and blood as the main treatment principle, and supplemented by regulating qi, resolving blood stasis, strengthening the spleen, and soothing the liver. At the molecular level, the mechanism of high-frequency medicine combination treatment for DOR with liver and kidney Yin deficiency syndrome was revealed, which provided a theoretical basis for the development and clinical application of subsequent DOR medicine.
- traditional Chinese medicine /
- diminished ovarian reserve /
- data mining /
- network pharmacology /
- mechanism

HTML全文

图 1 DOR证型分布

Figure 1. Distribution of DOR syndrome types

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图 2 高频药物四气频次分布

Figure 2. Frequency distribution of four properties of high-frequency medicines

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图 3 高频药物五味频次分布

Figure 3. Frequency distribution of five flavors of high-frequency medicines

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图 4 高频药物归经频次分布

Figure 4. Frequency distribution of meridian tropism of high-frequency medicines

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图 5 中医药治疗DOR高频药物网络化关联展示

Figure 5. Networked correlation display of high-frequency traditional Chinese medicines for treating DOR

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图 6 高频药物聚类分析柱状图

Figure 6. Cluster analysis histogram of high-frequency medicines

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图 7 补肾滋阴养血方活性成分-肝肾阴虚型DOR作用靶点网络

Figure 7. Network of active components of tonifying the kidney and nourishing Yin and blood formulas-action targets of DOR with liver and kidney Yin deficiency syndrome

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图 8 交集靶点相互作用网络关系

Figure 8. Interaction network relationships of intersecting targets

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图 9 基于MCC算法计算排名前10的补肾滋阴养血方治疗肝肾阴虚型DOR的Hub基因

Figure 9. Calculating the top 10 hub genes of tonifying the kidney and nourishing Yin and blood prescriptions for treating DOR with liver and kidney Yin deficiency syndrome based on MCC algorithm

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图 10 补肾滋阴养血方活性成分潜在靶点的富集分析(生物过程)

Figure 10. Enrichment analysis of potential targets of active components of tonifying the kidney and nourishing Yin and blood prescriptions (biological process)

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图 11 补肾滋阴养血方活性成分潜在靶点的通路注释

Figure 11. Pathway annotation of potential targets of active components in tonifying the kidney and nourishing Yin and blood prescriptions

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表 1 中医药治疗DOR的高频中药(排名前20)

Table 1. High-frequency traditional Chinese medicines for treating DOR (ranking in the top 20)

序号	药物	频次	频率/%	序号	药物	频次	频率/%
1	菟丝子	55	79.71	11	甘草	20	28.99
2	熟地	54	78.26	12	续断	19	27.54
3	当归	48	69.57	13	杜仲	19	27.54
4	白芍	37	53.62	14	白术	19	27.54
5	淫羊藿	27	39.13	15	香附	16	23.19
6	枸杞子	25	36.23	16	女贞子	16	23.19
7	山药	23	33.33	17	茯苓	16	23.19
8	川芎	22	31.88	18	柴胡	15	21.74
9	山茱萸	21	30.43	19	龟板	14	20.29
10	丹参	21	30.43	20	党参	14	20.29

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表 2 中医药治疗DOR高频药物二阶关联规则分析

Table 2. Second-order association rule analysis for high-frequency medicines for DOR treatment

前项	后项	支持度/%	置信度/%
菟丝子	熟地	70.88	83.92
熟地	菟丝子	69.62	85.45
当归	菟丝子	62.02	85.71
淫羊藿	菟丝子	35.44	85.71
淫羊藿	当归	35.44	82.14
枸杞子	菟丝子	32.91	100
枸杞子	熟地	32.91	84.61
山药	菟丝子	30.37	91.66
山药	熟地	30.37	83.33
川芎	当归	29.11	95.65
川芎	菟丝子	29.11	95.65
川芎	熟地	29.11	82.60
山茱萸	熟地	27.84	95.45
丹参	熟地	27.84	95.45
丹参	菟丝子	27.84	90.90
山茱萸	菟丝子	27.84	81.81
甘草	菟丝子	26.58	90.47
甘草	当归	26.58	85.71
甘草	熟地	26.58	80.95
杜仲	熟地	25.31	100

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表 3 中医药治疗DOR高频药物因子分析

Table 3. Factor analysis of high-frequency medicines for DOR treatment

公因子	中药组合	因子贡献率
1	白芍、杜仲、白术、茯苓、党参	13.11
2	当归、淫羊藿、川芎	10.43
3	丹参、女贞子、龟板	10.03
4	熟地、山药、山茱萸	8.70
5	香附、柴胡	8.36
6	菟丝子、枸杞子	8.28
7	甘草、续断	7.10

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表 4 高频药物聚类方

Table 4. Cluster formulas of high-frequency medicines

聚类方	中药组合
1	女贞子、龟板、丹参、香附、柴胡
2	山药、山茱萸
3	川芎、甘草、白术、党参、茯苓、杜仲、续断
4	淫羊藿
5	枸杞子
6	白芍
7	菟丝子、熟地、当归

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表 5 补肾滋阴养血方活性成分中药来源

Table 5. Source of active components of tonifying the kidney and nourishing Yin and blood prescriptions in traditional Chinese medicine

序号	MOL ID	化合物	中药来源
1	MOL000098	Quercetin	淫羊藿、枸杞子、菟丝子
2	MOL004373	Anhydroicaritin	淫羊藿
3	MOL004382	Yinyanghuo A	淫羊藿
4	MOL004384	Yinyanghuo C	淫羊藿
5	MOL004386	Yinyanghuo E	淫羊藿
6	MOL004425	Icariin	淫羊藿
7	MOL004367	Olivil	淫羊藿
8	MOL004391	8-(3-Methylbut-2-enyl)-2-phenyl-chromone	淫羊藿
9	MOL004394	Anhydroicaritin-3-O-alpha-L-rhamnoside	淫羊藿
10	MOL004388	6-Hydroxy-11, 12-dimethoxy-2, 2-dimethyl-1, 8-dioxo-2, 3, 4, 8-tetrahydro-1H-isochromeno[3, 4-h]isoquinolin-2-ium	淫羊藿
11	MOL000449	Stigmasterol	枸杞子、熟地、当归
12	MOL001979	LAN	枸杞子
13	MOL001323	Sitosterol alpha1	枸杞子
14	MOL006209	Cyanin	枸杞子
15	MOL007449	24-Methylidenelophenol	枸杞子
16	MOL009618	24-Ethylcholesta-5, 22-dienol	枸杞子
17	MOL009621	24-Methylenelanost-8-enol	枸杞子
18	MOL009622	Fucosterol	枸杞子
19	MOL009634	31-Norlanosterol	枸杞子
20	MOL009641	4alpha, 24-Dimethylcholesta-7, 24-dienol	枸杞子
21	MOL009642	4alpha-Methyl-24-ethylcholesta-7, 24-dienol	枸杞子
22	MOL009644	6-Fluoroindole-7-Dehydrocholesterol	枸杞子
23	MOL009646	7-O-Methylluteolin-6-C-beta-glucoside_qt	枸杞子
24	MOL009651	Cryptoxanthin monoepoxide	枸杞子
25	MOL009664	Physalin A	枸杞子
26	MOL009665	Physcion-8-O-beta-D-gentiobioside	枸杞子
27	MOL009681	Obtusifoliol	枸杞子
28	MOL009612	(24R)-4alpha-Methyl-24-ethylcholesta-7, 25-dien-3beta-ylacetate	枸杞子
29	MOL001558	Sesamin	菟丝子
30	MOL000354	Isorhamnetin	菟丝子
31	MOL005440	Isofucosterol	菟丝子
32	MOL006649	Sophranol	菟丝子
33	MOL001918	Paeoniflorgenone	白芍
34	MOL001921	Lactiflorin	白芍
35	MOL001924	Paeoniflorin	白芍
36	MOL001925	Paeoniflorin_qt	白芍
37	MOL001928	Albiflorin_qt	白芍
38	MOL000211	Mairin	白芍
39	MOL001910	11alpha, 12alpha-epoxy-3beta-23-dihydroxy-30-norolean-20-en-28, 12beta-olide	白芍
40	MOL001919	(3S, 5R, 8R, 9R, 10S, 14S)-3, 17-dihydroxy-4, 4, 8, 10, 14-pentamethyl-2, 3, 5, 6, 7, 9-hexahydro-1H-cyclopenta[a]phenanthrene-15, 16-dione	白芍

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