网络药理学与实验相结合探索柴胡清肝汤治疗肉芽肿性乳腺炎作用机制  

Exploration on Action Mechanism of Chaihu Qinggan Decoction in Treating Granulo⁃matous Mastitis Through Network Pharmacology Combined with Experimentation

作　　者：马丽娜 吴晶晶[1] 叶媚娜[1] 王冰[1] 殷玉莲[1] 周悦[1] 仲芫沅 程一凡 陈红风[1] MA Li'na;WU Jingjing;YE Meina;WANG Bing;YIN Yulian;ZHOU Yue;ZHONG Yuanyuan;CHENG Yifan;CHEN Hongfeng(Longhua Hospital Shanghai University of Traditional Chinese Medicine,Shanghai 200030,China)

机构地区：[1]上海中医药大学附属龙华医院,上海200030

出　　处：《新中医》2024年第23期16-24,共9页New Chinese Medicine

基　　金：上海市申康医院发展中心重大临床研究项目(SHDC2020CR2051B)。

摘　　要：目的:采用网络药理学和实验结合的方式,对柴胡清肝汤(CHQGT)治疗肉芽肿性乳腺炎(GM)的作用机制进行研究。方法:首先,通过公共数据库获取CHQGT活性成分、预测相应靶点及GM疾病靶点,应用Cytoscape软件构建成分-靶点网络;构建韦恩图,得到CHQGT治疗GM的作用靶点;并进行GO功能注释和KEGG通路富集分析。然后,进行分子对接以评估关键蛋白质与相关化合物的亲和力。最后,建立了GM大鼠模型,验证预测信号通路中涉及的主要靶蛋白,以探讨CHQGT抑制疾病进展的机制。结果:研究显示共挖掘到CHQGT中235种活性成分及260个潜在靶点,GM疾病224个相关靶点,得到柴胡清肝汤-疾病共同靶点27个。GO功能注释分析共涉及1400个生物过程,KEGG通路富集分析涉及68条信号通路。分子对接显示IL-1β与CHQGT中的主要成分槲皮素良好结合。动物研究表明,CHQGT给药不仅减缓了GM大鼠肿块进展,而且还减轻了病变区炎症浸润情况,抑制了NF-κB表达和血清肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)、白细胞介素-6(IL-6)水平。结论:网络药理学分析预测,CHQGT可调节多种成分、靶点和途径,从而对GM产生治疗作用。动物实验证实,CHQGT在GM治疗中的作用机制是通过调节NF-κB信号通路和IL-1β、IL-6等关键蛋白,从而抑制炎症进展。Objective:To study the action mechanism of Chaihu Qinggan Decoction(CHQGT)in the treatment of granulomatous mastitis(GM)by means of network pharmacology combined with experimentation.Methods:First,the active components of CHQGT were obtained from public database,and the corresponding targets and GM disease targets were predicted.The component-target network was constructed by Cytoscape software;the target of CHQGT in GM treatment was obtained by constructing Venn diagram.GO function annotation and KEGG pathway enrichment analysis were performed.Molecular docking is then performed to assess the affinity of the key protein to the relevant compound.Last,a GM rat model was established to verify the main target proteins involved in the predictive signaling pathway,so as to explore the mechanism of CHQGT inhibiting disease progression.Results:The study showed that 235 active ingredients and 260 potential targets in CHQGT and 224 targets related to GM disease were excavated,and 27 common targets of CHQGT and disease were obtained.Go envichment analysis involves 1400 biological processes,while KEGG pathway enrichement analysis involves 68 signaling pathways.Molecular docking showed that IL-1βwas well bound to Quercetin,the main component of CHQGT.Animal studies showed that CHQGT administration not only slowed down the progression of mass in GM rats but also reduced inflammatory infiltration in the lesion area,inhibited the expression of NF-κB and serum levels of tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β)and interleukin-6(IL-6).Conclusion:Network pharmacological analysis predicted that CHQGT could regulate various components,targets and pathways,so as to have therapeutic effects on GM.Animal experiments have confirmed that the action mechanism of CHQGT in GM treatment is to inhibit the progression of inflammation by regulating the NF-κB signaling pathway and key proteins such as IL-1βand IL-6.

关 键 词：肉芽肿性乳腺炎 柴胡清肝汤 网络药理学 分子对接 NF-ΚB信号通路 

分 类 号：R655.8[医药卫生—外科学]