基于网络药理学和实验验证探讨阳和汤治疗肉芽肿性小叶性乳腺炎作用机制  

Exploration on Mechanism of Yanghe Decoction in the Treatment of Granulomatous Lobular Mastitis Based on Network Pharmacology and Experimental Validation

作　　者：李昊钰 于敏敏 张梦棣 任英楠 梁爽 秦瑜婧 李静蔚[2] LI Haoyu;YU Minmin;ZHANG Mengdi;REN Yingnan;LIANG Shuang;QIN Yujing;LI Jingwei(The First Clinical Medical College of Shandong University of Traditional Chinese Medicine,Jinan 250000,China;Affiliated Hospital of Shandong University of Traditional Chinese Medicine,Jinan 250000,China)

机构地区：[1]山东中医药大学第一临床医学院,山东济南250000 [2]山东中医药大学附属医院,山东济南250000

出　　处：《中国中医药信息杂志》2025年第3期34-41,共8页Chinese Journal of Information on Traditional Chinese Medicine

基　　金：山东省自然科学基金中医药联合基金(ZR2022LZY019);山东省中医药科技项目(Z-2023002T);济南市临床医学科技创新计划(202134004);齐鲁医派中医药特色技术整理推广项目(2022年)。

摘　　要：目的运用网络药理学及分子对接探究阳和汤治疗肉芽肿性小叶性乳腺炎(GLM)的潜在靶点及通路,并进行实验验证。方法通过TCMSP、TCM-ID数据库及文献检索并筛选阳和汤活性成分和靶点,通过GeneCards、OMIM数据库检索GLM靶点,对药物靶点与疾病靶点取交集,构建蛋白相互作用网络,并进行GO和KEGG通路富集分析,对主要成分与关键靶点进行分子对接。将60只SD大鼠随机分为空白组、模型组、泼尼松龙组(0.005 g/kg)及阳和汤低、中、高剂量组(2.5、5.0、10.0 g/kg),除空白组外,其余组均构建GLM模型,各给药组予相应药物干预,连续14 d。记录大鼠体质量及乳腺肿块大小,采集乳腺超声声像图并进行炎症指数评分,HE染色观察大鼠乳腺组织形态,ELISA检测血清白细胞介素(IL)-1β、IL-6、肿瘤坏死因子-α(TNF-α)含量,Western blot检测乳腺组织IL-1β、IL-6、TNF-α、核因子-κB抑制蛋白α(IκBα)、Toll样受体4(TLR4)、核因子-κB p65(p65)蛋白表达。结果筛选出阳和汤有效成分140种、靶点363个,与GLM交集靶点32个,主要涉及NF-κB、PI3K-Akt信号通路等,分子对接显示主要成分与关键靶点结合活性良好。与空白组比较,模型组大鼠乳房明显红肿,肿块大且乳腺炎症指数评分显著升高(P<0.01),超声可探及范围较大的片状低回声区,乳腺小叶内多种炎性细胞浸润并形成微小脓肿,模型组大鼠血清IL-1β、IL-6及TNF-α含量显著增加(P<0.01),乳腺组织IL-1β、IL-6、TNF-α、TLR4、p65蛋白表达显著升高(P<0.01),IκBα蛋白表达显著降低(P<0.05);与模型组比较,各治疗组大鼠乳房红肿均改善,肿块缩小,以泼尼松龙组及阳和汤高剂量组肿块缩小明显(P<0.05),泼尼松龙组及阳和汤各剂量组炎症指数评分不同程度下降(P<0.01),超声可见低回声区范围较小,乳腺小叶炎性细胞浸润减轻,肉芽肿及脓肿减少,泼尼松龙组及阳和汤各剂量组血清IL-1β、TNF-α含量明显�Objective To explore the potential targets and pathways of Yanghe Decoction for the treatment of granulomatous lobular mastitis(GLM)using network pharmacology and molecular docking;To experimentally validate its mechanism.Methods Active components and targets of Yanghe Decoction were screened through TCMSP and TCM-ID.GLM targets were retrieved from GeneCards and OMIM databases,the intersection of drug targets and disease targets was taken,and a protein interaction network was constructed.GO and KEGG pathway enrichment analysis was performed.Molecular docking of main components and key targets was conducted.Totally 60 SD rats were randomly divided into blank group,model group,prednisolone group(0.005 g/kg),and Yanghe Decoction low,medium-and high-dosage groups(2.5,5.0,10.0 g/kg).Except for the blank group,GLM models were constructed for all other groups,and corresponding drug interventions were given to each treatment group for 14 consecutive days.The body mass and breast mass size of rats were recorded,breast ultrasound images were collected,and the inflammatory index score was scored.The pathological morphology of rat breast tissue was observed through HE staining.ELISA was used to detect the contents of IL-1β,IL-6 and TNF-αin serum.Western blot was used to detect the protein expressions of IL-1β,IL-6,TNF-α,IκBα,TLR4 and p65 in breast tissue.Results Yanghe Decoction was screened for 140 active components,363 targets,and 32 intersecting targets with GLM,mainly involving NF-κB,PI3K-Akt signaling pathway,etc.Molecular docking showed that the main components had good binding activities with key targets.Compared with the blank group,rats in the model group showed obvious redness and swelling of the breasts with a large range of lumps and a significant increase in mammary inflammation index score(P<0.01),and ultrasound could detect a large range of patchy hypoechoic areas,and pathological changes showed a variety of inflammatory cell infiltration in the mammary lobules and the formation of tiny abscesses,and th

关 键 词：肉芽肿性小叶性乳腺炎 阳和汤 网络药理学 作用机制 大鼠 

分 类 号：R285[医药卫生—中药学]