国家中药复方专利内治卵巢囊肿的用药规律与作用机制研究  

Medication Rules and Mechanism of Internal Therapy of Traditional Chinese Medicine Compound Patents in the Treatment of Ovarian Cysts

作　　者：张凯民 萧绮俐 郭桢玉 邓嘉颖 周慧萍 周子添 王君玉 黄江鑫 凌静[8] 刘瑾 ZHANG Kaimin;XIAO Qili;GUO Zhenyu;DENG Jiaying;ZHOU Huiping;ZHOU Zitian;WANG Junyu;HUANG Jiangxin;LING Jing;LIU Jin(The Fifth Clinical Medical College,Guangzhou University of Chinese Medicine,Guangzhou 510405,China;the Second Clinical Medical College,Guangzhou University of Chinese Medicine,Guangzhou 510405,China;the First Clinical Medical College,Guangzhou University of Chinese Medicine,Guangzhou 510405,China;School of Public Health and Management,Guangzhou University of Chinese Medicine,Guangzhou 510006,China;Foshan Clinical Medical College,Guangzhou University of Chinese Medicine,Guangdong Foshan 528000,China;the Fourth Clinical Medical College,Guangzhou University of Chinese Medicine,Guangzhou 510006,China;Clinical Medical College of Acupuncture and Rehabilitation,Guangzhou University of Chinese Medicine,Guangzhou 510006,China;Dept.of Gynecology,Shenzhen Traditional Chinese Medicine Hospital,Guangdong Shenzhen 518033,China)

机构地区：[1]广州中医药大学第五临床医学院,广州510405 [2]广州中医药大学第二临床医学院,广州510405 [3]广州中医药大学第一临床医学院,广州510405 [4]广州中医药大学公共卫生与管理学院,广州510006 [5]广州中医药大学佛山临床医学院,广东佛山528000 [6]广州中医药大学第四临床医学院,广州510006 [7]广州中医药大学针灸康复临床医学院,广州510006 [8]深圳市中医院妇科,广东深圳518033

出　　处：《中国医院用药评价与分析》2025年第2期165-171,175,共8页Evaluation and Analysis of Drug-use in Hospitals of China

基　　金：广东省中医药局科研项目(No.20212197);深圳市“医疗卫生三名工程”项目资助(No.SZZYSM202211006)。

摘　　要：目的:基于国家知识产权局专利数据库,系统分析内服中药复方专利治疗卵巢囊肿(OC)的用药规律及作用机制,并结合细胞实验验证相关结果。方法:筛选专利文献,构建中药复方数据集,分析得到核心药物。利用中药系统药理学数据库与分析平台和GeneCards数据库获取活性成分和靶点,通过STRING数据平台和UniProt数据库标准化处理。使用Veeny平台得到交集靶点,使用Cytoscape软件绘制网络图,使用STRING数据平台获取蛋白质-蛋白质相互作用网络,使用Metascape数据库进行富集分析,使用AutoDockTools软件进行分子对接,采用细胞增殖-毒性检测法检测细胞存活率,采用蛋白质印迹法检测蛋白表达量。结果:(1)纳入104篇专利文献,含104首处方和351种中药,确定三棱、莪术、当归、桃仁为核心药物。(2)筛选出38个治疗OC的交集靶点,关键活性成分包括刺芒柄花素、β-谷甾醇和豆甾醇。核心靶点为前列腺素内酰胺合酶2(PTGS2)、半胱天冬酶3(CASP3)、过氧化物酶体增殖物激活受体γ(PPARG)。基因本体功能富集分析得到激素反应、细胞器外膜及蛋白质结构域特异性结合等生物过程、分子功能及细胞组分。京都基因与基因组百科全书通路富集分析分析显示,白细胞介素17、晚期糖基化终末产物(AGE)-AGE受体为主要信号通路。分子对接显示,活性成分与靶点蛋白结合稳定。(3)刺芒柄花素浓度为20~80μmol/L时对人卵巢颗粒细胞(KGN)无毒性,浓度为100μmol/L时细胞存活率下降。与模型组(5μg/mL的脂多糖,孵育12 h)比较,刺芒柄花素组(低、中、高剂量组)PTGS2、CASP3蛋白表达显著降低(P<0.05),刺芒柄花素高剂量组PPARG表达升高(P<0.05),差异均有统计学意义。结论:通过数据挖掘分析发现,内治OC的中药复方专利多为活血行气、化瘀消积类药物,其关键活性成分刺芒柄花素、β-谷甾醇与豆甾醇主要作用于PTGS2、CASP3和PPARG等核OBJECTIVE:Based on the patent database of the China National Intellectual Property Administration,to systematically analyze the medication rules and mechanism of internal therapy of traditional Chinese medicine compound patents in the treatment of ovarian cysts(OC),so as to validate the relevant results through cell experiments.METHODS:The patent literature was screened to construct the data set of traditional Chinese medicine compound patents and obtain the core drugs after analysis.The Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform and GeneCards database were used to obtain active components and targets,STRING and UniProt were used to conduct standardized processing.Veeny was used to obtain intersecting targets,Cytoscape was used to draw the network,STRING was used to obtain protein-protein interaction network,Metascape was used to conduct enrichment analysis,AutoDockTools was used to conduct molecular docking,CCK-8 method was used to measure the cell viability and Western blotting was used to measure protein expression quantity.RESULTS:(1)A total of 104 patent studies including 104 formulas and 351 traditional Chinese medicine were enrolled,so that Sparganii rhizoma,Curcumae rhizoma,Angelicae sinensis radix,and Persicae semen were identified as the core drugs.(2)A total of 38 intersecting targets for the treatment of OC were screened out,the key active components included formononetin,β-sitosterol and stigmasterol.The core targets were PTGS2,CASP3 and PPARG.Biological processes,molecular functions and cellular components such as hormone response,organelle outer membrane and protein structural domain-specific binding were obtained from the Gene Ontology functional enrichment analysis.Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis indicated that interleukin 17 and advanced glycosylation end product(AGE)-AGE receptor were the major signaling pathways.Molecular docking indicated stable binding between active ingredient and target protein.(3)Formononetin showe

关 键 词：卵巢囊肿 中药复方专利 数据挖掘 网络药理学 分子对接 刺芒柄花素 人卵巢颗粒细胞 

分 类 号：R932[医药卫生—生药学] R984[医药卫生—药学]