基于网络药理学和实验验证探讨庞氏安胎止血汤治疗先兆流产的作用机制  

Mechanism of Pangshi Antai Zhixue Decoction(庞氏安胎止血汤)in the Treatment of Threatened Abortion Based on Network Pharmacology and Experimental Verification

作　　者：贾梦媛 张大伟[2] 马丽亚[1] 蔡园园 杨一桐 王丹亚 王静怡 JIA Mengyuan;ZHANG Dawei;MA Liya;CAI Yuanyuan;YANG Yitong;WANG Danya;WANG Jingyi(Henan University of Chinese Medicine,Zhengzhou 450046;The Third Affiliated Hospital of Henan University of Chinese Medicine,Zhengzhou 450008;Henan Province Hospital of Traditional Chinese Medicine,Zhengzhou 450000)

机构地区：[1]河南中医药大学,郑州450046 [2]河南中医药大学第三附属医院,郑州450008 [3]河南省中医院,郑州450000

出　　处：《中药药理与临床》2023年第7期33-40,共8页Pharmacology and Clinics of Chinese Materia Medica

基　　金：河南省中医药科学研究专项课题重点课题(编号:2023ZYZD09、20-21ZY1053);河南省科技攻关重点项目(编号:222102310139);河南省高等学校重点科研项目(编号:17A360023)。

摘　　要：目的:基于网络药理学研究庞氏安胎止血汤治疗先兆流产(Threatended abortion)的主要作用机制。方法:通过TCMSP数据库、SwissTarget Prediction数据库以及相关文献获取庞氏安胎止血汤主要活性成分及潜在靶点;检索GeneCards、DrugBank、OMMI、DisGeNET、TTD数据库获取先兆流产相关靶点,将二者靶点取交集获取庞氏安胎止血汤治疗先兆流产的潜在作用靶点;STRING平台构建PPI网络,进行拓扑分析获取核心靶点;利用Metascape平台对交集靶点分别进行GO功能和KEGG通路富集分析;运用Cytoscape 3.9.1软件绘制“庞氏安胎止血汤成分-靶点-通路”网络图;运用AutoDock vina 1.5.6软件对核心基因和主要活性成分进行分子对接验证。以动物实验进行验证,构建血热型先兆流产大鼠模型,Western blot、免疫组化法检测大鼠模型子宫蜕膜组织中SRC、FOS、ESR1的表达,HE染色观察大鼠蜕膜组织病理学变化。结果:庞氏安胎止血汤包括槲皮素、木犀草素、山柰酚、汉黄芩素、刺芒柄花素、黄芩素、等核心成分;拓扑分析得到SRC、JUN、STAT3、STAT1、FOS、EGFR以及AKT1核心靶点7个;GO分析获得主要涉及对无机物反应、细胞调节、腺体发育、等细胞生物学过程;KEGG通路富集分析获得250条信号通路,主要与癌症信号通路、糖基化终末产物-糖基化终末产物受体(AGE-RAGE)信号通路、化学致癌-受体激活、内分泌抵抗、PI3K-AKT信号通路相关。分子对接提示庞氏安胎汤主要活性成分与核心蛋白结合稳定。动物实验表明,与正常对照组相比,模型对照组SRC、FOS、ESR1蛋白表达显著上调(P<0.01);与模型对照组相比,地屈孕酮3.02 mg/kg组、庞氏安胎止血汤44、88 g/kg组SRC、FOS、ESR1蛋白表达显著下调(P<0.01)。结论:庞氏安胎止血汤是通过多成分、多靶点、多途径协同作用来治疗先兆流产。Objective:To explore the mechanism of Pangshi Antai Zhixue Decoction(庞氏安胎止血汤)in the treatment of threatened abortion based on network pharmacology.Methods:The main active components and potential targets of Pangshi Antai Zhixue Decoction were obtained from the TCMSP database,SwissTarget Prediction database,and related literature.GeneCards,DrugBank,OMMI,DisGeNET,and TTD were searched for the targets related to threatened abortion,and the intersection of the two targets was obtained to obtain the potential targets of Pangshi Antai Zhixue Decoction in the treatment of threatened abortion.The STRING platform was used to build a PPI network,followed by topological analysis to obtain core targets.The GO function and KEGG pathway enrichment of intersection targets were analyzed by the Metascape platform.Cytoscape 3.9.1 software was used to draw the component-target-pathway network of Pangshi Antai Zhixue Decoction.AutoDock vina 1.5.6 software was used to verify the molecular docking of core genes to main active components.Animal experiments were used for verification,and the rat model of threatened abortion was constructed.The expression of SRC,FOS,and ESR1 in rat decidual tissues was detected by Western blot and immunohistochemistry,and the histopathological changes in rat decidual tissues were observed by HE staining.Results:The core chemical components of Pangshi Antai Zhixue Decoction included quercetin,luteolin,kaempferol,wogonin,formononetin,and baicalein.Topological analysis revealed seven core targets including SRC,JUN,STAT3,STAT1,FOS,EGFR,and AKT1.As revealed by GO analysis,biological processes mainly included the response to inorganic substances,cell regulation,and gland development.KEGG pathway enrichment analysis obtained 250 signaling pathways,mainly related to cancer signaling pathway,advanced glycation end product and their receptor(AGE-RAGE)signaling pathway,chemical carcinogens-receptor activation,endocrine resistance,and phosphoinositide 3-kinase(PI3K)/protein kinase B(Akt)signaling pathw

关 键 词：庞氏安胎止血汤 先兆流产 网络药理学 分子对接 实验验证 

分 类 号：R285[医药卫生—中药学]