“血水同治”的桂枝茯苓丸治疗子宫内膜异位症网络药理学机制研究  

Network Pharmacological Mechanism of Guizhi Fuling Pill in the Treatment of Endometriosis by Blood Stasis and Phlegm-Dispelling Therapy

作　　者：谢韬 杨碧蓉[1] 何培芝[1] 周华[1] XIE Tao;YANG Birong;HE Peizhi;ZHOU Hua(Dept.of Gynecology,Shuguang Hospital,Shanghai University of Traditional Chinese Medicine,Shanghai 201203,China)

机构地区：[1]上海中医药大学附属曙光医院妇科,上海201203

出　　处：《中国医院用药评价与分析》2022年第6期652-656,660,共6页Evaluation and Analysis of Drug-use in Hospitals of China

基　　金：上海市海派中医流派传承人才培养项目(No.沪卫计中发办LPRC2017032)。

摘　　要：目的:探讨子宫内膜异位症中医常用药物桂枝茯苓丸的网络药理学机制。方法:通过数据库结合文献挖掘选出桂枝茯苓丸(桂枝、茯苓、赤芍、桃仁和牡丹皮)的主要活性成分,收集其靶点,同时通过疾病数据库获取子宫内膜异位症靶点。分析桂枝茯苓丸与子宫内膜异位症的共有靶点,选取共有靶点及其邻居节点构建“成分靶点-疾病靶点”核心网络,筛选出关键靶点进行基因本体(GO)功能富集分析和京都基因与基因组百科全书(KEGG)通路富集分析,分析桂枝茯苓丸治疗EMT可能的生物过程和信号通路。结果:子宫内膜异位症靶点1 600个;桂枝茯苓丸经过筛选,明确活性成分达51个,靶点823个;病、药共有靶点190个。GO功能富集分析结果表明,桂枝茯苓丸可能是通过调节大麻素受体1(CB1)、大麻素受体2(CB2)、红细胞沉降率(ESR)、孕激素受体(PGR)和花生四烯酸-5-脂加氧酶(ALOX-5)等靶点,上述靶点与蛋白质、DNA及酶结合紧密相关,并涉及细胞凋亡、增殖和转录过程的正调节等多个生物过程。KEGG通路富集分析结果表明,上述靶点与丝裂原激活的蛋白激酶(MAPK)等多条信号通路的调控相关。结论:通过网络药理学方法与技术,发现桂枝茯苓丸可通过调节CB1、CB2、ESR、PGR和ALOX-5等靶点,进而调控MAPK信号通路,积极干预了子宫内膜异位症增殖抗凋亡、黏附、侵袭和血管生成等病理过程,发挥其“血水同治”的作用。OBJECTIVE: To explore the network pharmacological mechanism of Guizhi Fuling pill in the treatment of endometriosis. METHODS: The main active ingredients of Guizhi Fuling pill(Guizhi, Fuling, Chishao, Taoren, Mudanpi) were selected by database and literature mining, and the targets were collected. Meanwhile, endometriosis targets were obtained by disease database. The common targets of Guizhi Fuling pill and endometriosis were analyzed, and the common targets and the neighbor nodes were selected to construct the “ingredient target-disease target” core network. Key targets were screened for Gene Ontology(GO) functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis, to analyze the possible biological process and signal pathway of Guizhi Fuling pill in the treatment of EMT. RESULTS: Totally 1 600 endometriosis targets were obtained. After screening, 51 active ingredients and 823 targets were identified in Guizhi Fuling pill, there were 190 targets for diseases and drugs. Results of GO functional enrichment analysis showed that Guizhi Fuling pill might regulate modulating cannabinoid receptor 1(CB1), cannabinoid receptor 2(CB2), erythrocyte sedimentation rate(ESR), progesterone receptor(PGR) and ALOX-5 and other targets, which were closely related to protein, DNA and enzyme binding, and were involved in many biological processes such as apoptosis, proliferation and positive regulation of transcription. KEGG pathway enrichment analysis showed that the above targets were related to the regulation of mitogen-activated protein kinase(MAPK) and other signaling pathways. CONCLUSIONS: Through network pharmacology, it is found that Guizhi Fuling pill could regulate the MAPK signaling pathway by regulating the targets of CB1, CB2, ESR, PGR and ALOX-5, and intervene in the pathological processes of endometriosis such as proliferation, anti-apoptosis, adhesion, invasion and angiogenesis, and exert the mechanism of “blood stasis and phlegm-dispelling”.

关 键 词：血水同治 桂枝茯苓丸 网络药理学 子宫内膜异位症 

分 类 号：R932[医药卫生—生药学] R96[医药卫生—药学]