| 引用本文:孙建华1，2，张逸1，陈春林3，陈萍2，周立2，翟凤霞4，郭淼2.基于网络药理学探讨加味当归芍药散对子宫内膜异位症痛经的作用机制及实验验证[J].世界中医药,2024,(13):. |
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| 基于网络药理学探讨加味当归芍药散对子宫内膜异位症痛经的作用机制及实验验证 |
| Mechanism of Modified Danggui Shaoyao Powder in Treatment of Dysmenorrhea of Endometriosis Based on Network Pharmacology and Experimental Verification |
| 投稿时间：2023-01-04 |
| DOI：10.3969/j.issn.1673-7202.2024.13.009 |
| 中文关键词: 加味当归芍药散 网络药理学 子宫内膜异位症 痛经 分子对接 作用机制 |
| English Keywords:Modified Danggui Shaoyao Powder Network pharmacology Endometriosis Dysmenorrhea Molecular docking Mechanism |
| 基金项目:国家自然科学基金青年科学基金项目(82004412);河南省中医药科学研究专项（2021ZY2008）;河南中医药大学博士科研启动基金项目(RSBSJJ2019-29);胡玉荃全国名老中医药专家传承工作室建设项目(CZ0098);河南中医药大学重点学科建设项目(15102044-2020);河南省第二批中医药青苗人才培养项目（豫卫中医函〔2021〕16号） |
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| 中文摘要: |
| 目的：基于网络药理学探讨加味当归芍药散治疗子宫内膜异位症（EMs）痛经的作用机制。方法：利用中药系统药理学数据库与分析平台（TCMSP）、人类孟德尔遗传在线数据库（OMIM）、人类基因数据库（GeneCards）、人类疾病相关基因与突变位点信息数据库（DisGeNET）、疗效靶点数据库（TTD）等数据库分析组方活性成分及潜在作用靶点，构建加味当归芍药散活性成分-EMs痛经靶点网络，并对核心靶点进行基因本体（GO）及京都基因与基因组百科全书（KEGG）通路富集分析，应用分子对接vina（Autodock vina）软件对组方潜在活性成分及核心靶点进行分子对接，并采用实时荧光定量逆转录聚合酶链反应（RT-qPCR）及蛋白免疫印记法初步验证组方对EMs小鼠模型子宫内膜预测靶点mRNA及相关蛋白表达的影响。结果：组方筛选出活性成分86个，其治疗EMs痛经对应的交集靶点共64个，其中度值较高的靶点包括表皮生长因子受体（EGFR）、肿瘤抑制基因p53（TP53）、前列腺素内过氧化物合酶2（PTGS2）、血管内皮生长因子A（VEGFA）、丝氨酸/苏氨酸蛋白激酶1（AKT1）、白细胞介素6（IL-6）、基序趋化因子配体8（CXCL8）、基质金属蛋白酶9（MMP9）等。GO功能富集分析共得到1990个条目，KEGG通路分析涉及雌激素、黏着斑等127条通络。分子对接结果显示，组方核心成分槲皮素与VEGFA、AKT1、低氧诱导因子1A（HIF1A）等关键靶点具有良好的结合力。验证实验显示，加味当归芍药散可显著下调EMs小鼠模型VEGFA、CXCL8、TP53等mRNA及MMP9、环氧合酶-2（COX-2）蛋白表达水平。结论：加味当归芍药散的核心成分可调控EMs痛经的多个靶点，其作用机制可能和调控细胞侵袭、雌激素、免疫、炎症反应等信号通路相关。 |
| English Summary: |
| To explore the mechanism of modified Danggui Shaoyao Powder in treating dysmenorrhea of endometriosis(EMs) based on network pharmacology.Methods:The active ingredients and potential targets of the formula were analyzed using various databases，including the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)，Online Mendelian Inheritance in Man(OMIM)，GeneCards，DisGeNET，and the Therapeutic Target Database(TTD).A network of active ingredients of modified Danggui Shaoyao Powder and EMs dysmenorrhea targets was constructed，and Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analyses were performed for core targets.Molecular docking between potential active ingredients and core targets was conducted using Autodock Vina software.Real-time quantitative reverse transcription polymerase chain reaction(RT-qPCR) and western blot were used to preliminarily verify the effect of the formula on mRNA and related protein expression in the endometrium of the EMs mouse model.Results:A total of 86 active ingredients were screened from the formula，corresponding to 64 intersecting targets for the treatment of EMs dysmenorrhea.High-degree targets included epidermal growth factor receptor(EGFR)，tumor suppressor gene p53(TP53)，prostaglandin-endoperoxide synthase 2(PTGS2)，vascular endothelial growth factor A(VEGFA)，serine/threonine protein kinase 1(AKT1)，interleukin-6(IL-6)，chemokine ligand 8(CXCL8)，and matrix metalloproteinase 9(MMP9).GO functional enrichment analysis yielded 1 990 entries，and KEGG pathway analysis involved 127 pathways such as estrogen and focal adhesion.Molecular docking results indicated that quercetin，a core component of the formula，had good binding affinity with key targets such as VEGFA，AKT1，and hypoxia-inducible factor 1A(HIF1A).Validation experiments showed that modified Danggui Shaoyao Powder significantly downregulated the mRNA levels of VEGFA，CXCL8，and TP53，as well as the protein levels of MMP9 and cyclooxygenase-2(COX-2) in the EMs mouse model.Conclusion:The core components of modified Danggui Shaoyao Powder can modulate multiple targets related to EMs dysmenorrhea，and the underlying mechanism of action may involve the regulation of cell invasion，estrogen，immune，and inflammatory response signaling pathways. |
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