| 摘要: |
| 目的 利用数据挖掘的方法探究历代医家治疗肥胖型多囊卵巢综合征（PCOS）的处方规律，归纳核心处方与药物，并利用网络药理学探讨核心处方的潜在物质基础与作用机制，为中医药治疗肥胖型PCOS提供参考。方法 以《中华医典》为资料来源，利用Excel 2018建立肥胖型PCOS处方数据库，借助SPSS Modeler 18及Gephi0.9.7软件对符合肥胖型PCOS表现的处方药物进行关联分析。利用中药系统药理学数据库与分析平台（TCMSP）获取核心药对的成分及靶基因，利用人类基因数据库（GeneCard）和在线人类孟德尔遗传数据库（OMIM）获取肥胖型PCOS靶基因，进一步获取核心药物靶基因与肥胖型PCOS靶基因的交集基因。利用Cytoscape 3.7.1软件构建核心药物活性成分-交集基因网络，并利用可视化和集成发现数据库（DAVID）进行组织富集分析。结果 共得到符合肥胖型PCOS的处方47首，涉及中药98味，使用频次≥5的中药为茯苓、半夏、甘草、陈皮、川芎、香附、白术、当归、苍术、南星、人参、滑石、枳壳、白芍、黄连、地黄、橘红、砂仁,有强关联的核心药对组合为半夏、陈皮、茯苓、甘草（二陈汤）。利用TCMSP数据库获得二陈汤的药物成分125个、靶基因218个，利用GeneCard数据库及OMIM获得肥胖型PCOS靶基因2 962个，获得肥胖型PCOS靶基因与核心药物靶基因的交集基因149个。网络药理学分析显示，度值较高的药物活性成分有槲皮素、山奈酚、芒柄花素等，度值较高的靶基因包括前列腺素内过氧化物合酶2、雌激素受体1、雄激素受体等。组织富集分析结果显示，交集靶基因主要富集在胎盘、肝脏、肺、上皮等组织。结论 数据挖掘结果提示，历代医家治疗肥胖型PCOS时以益气健脾、燥湿化痰为主要原则，同时佐以养血调经的药物。网络药理学结果验证了古文献分析结果，提示黄酮类化合物可能通过调控激素受体改善肥胖型PCOS。 |
| 关键词: 多囊卵巢综合征 痰湿 闭经 不孕 组织富集分析 |
| DOI：10.16781/j.CN31-2187/R.20210531 |
| 投稿时间：2021-05-21修订日期：2021-08-26 |
| 基金项目:国家自然科学基金（81973896，82004408），上海市科学技术委员会中医引导项目（19401930200），上海市青年科技英才扬帆计划项目（20YF1448600），中国博士后科学基金面上项目（2020M68681337），上海市名老中医学术经验研究工作室建设项目（SHGZS-202240）. |
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| Mechanism of Erchen decoction in treating obese polycystic ovary syndrome based on ancient literature mining and network pharmacology |
| CAI Mengcheng1,ZHOU Zhihao2,JIN Yongsheng3,YU Chaoqin4* |
(1. Department of Rehabilitation Medicine and Physiotherapy, Naval Medical Center, Naval Medical University (Second Military Medical University), Shanghai 200052, China;
2. Department of Traditional Chinese Medicine, No. 929 Hospital of PLA Navy, Shanghai 200433, China;
3. Department of Organic Chemistry, School of Pharmacy, Naval Medical University (Second Military Medical University), Shanghai 200433, China;
4. Department of Traditional Chinese Medicine (Gynecology), School of Traditional Chinese Medicine, Naval Medical University (Second Military Medical University), Shanghai 200433, China
*Corresponding author) |
| Abstract: |
| Objective To explore the prescription rules of ancient physicians in the treatment of obese polycystic ovary syndrome (PCOS) by data mining, summarize the core prescriptions and drugs and explore the potential material basis and mechanism of core prescriptions using network pharmacology, so as to provide a reference for traditional Chinese medicine (TCM) treatment of obese PCOS. Methods Based on the Chinese Medical Code, a prescription database was established by Excel 2018. The ancient prescriptions of obese PCOS were analyzed by SPSS Modeler 18 and Gephi 0.9.7 software. Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) was used to obtain the components and targets of the core prescriptions. The Human Gene Database (GeneCard) and Online Mendelian Inheritance in Man Database (OMIM) were used to obtain the disease targets, and then intersection genes of drug targets and disease targets were obtained. Cytoscape 3.7.1 software was used to construct the active components-intersection genes network, and Database for Annovation, Visualization, and Integrated Discovery (DAVID) was used for tissue enrichment analysis. Results A total of 47 prescriptions for obese PCOS were obtained, involving 98 kinds of TCMs. The TCMs with frequency ≥5 were Poria, Rhizoma Pinelliae, Radix Glycyrrhizae, Pericarpium Citri Reticulatae, Radix chuanxiong, Rhizoma Cyperi, Rhizoma Atractylodis macrocephalae, Radix Angelicae sinensis, Rhizoma Atractylodis, Rhizoma Arisaematis, Radix Ginseng, Talcum, Fructus Aurantii, Radix Paeoniae Alba, Rhizoma Coptidis, Radix Rehmanniae, Citri Exocarpium Rubrum, and Fructus Amomi. The core drug pair combination with strong correlation was Rhizoma Pinelliae, Pericarpium Citri Reticulatae, Poria, and Radix Glycyrrhizae (Erchen decoction). A total of 125 components and 218 target genes were obtained from TCMSP database; 2 962 disease target genes were obtained from GeneCard and OMIM, and 149 intersection genes of obese PCOS target genes and core drug target genes were obtained. Network pharmacology showed the active ingredients of the drugs with high degree values included quercetin, kaempferol, and formononetin, and the target genes with high degree values included prostaglandin endoperoxide synthase 2, estrogen receptor 1, and androgen receptor. The tissue enrichment analysis showed that the intersection target genes were mainly enriched in the placenta, liver, lung, and epithelium. Conclusion The data mining results suggest that the main principle of treating obese PCOS is to dry dampness, remove phlegm, benefit Qi, and strengthen spleen, while supplemented with drugs that nourish blood and regulate menstruation. The network pharmacology results have verified the results of ancient literature analysis, suggesting that flavonoids may improve obese PCOS by modulating hormone receptors. |
| Key words: polycystic ovary syndrome phlegm dampness amenorrhea infertility tissue enrichment analysis |
