基于网络药理学、分子对接和实验验证探讨白虎汤治疗急性肺损伤作用机制  

Exploration on Mechanism of Baihu Decoction in Treating Acute Lung Injury Based on Network Pharmacology,Molecular Docking and Experimental Verification

作　　者：胡转楠 陈佳骏 吴显伟 周伟[1] 邱磊 张少言[1] 鹿振辉[1] HU Zhuannan;CHEN Jiajun;WU Xianwei;ZHOU Wei;QIU Lei;ZHANG Shaoyan;LU Zhenhui(Institute of Respiratory Diseases,Longhua Hospital of 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呼吸疾病研究所,上海200030

出　　处：《中国中医药信息杂志》2024年第3期19-25,共7页Chinese Journal of Information on Traditional Chinese Medicine

基　　金：国家自然科学基金(82174286);上海市科学技术委员会项目(21Y21920400、20Y21900200、22XD1423500);上海中医药大学附属龙华医院院级课题(Y21002、AJ046);上海市申康中心项目(SHDC2020CR2006A);上海市浦东新区卫生健康委员会卫生计生科研项目(PW2020D-1);上海市徐汇区卫生健康委员会重要疾病联合攻关项目(XHLHGG202107)。

摘　　要：目的 基于网络药理学、分子对接技术探讨白虎汤治疗急性肺损伤的作用机制,并进行实验验证。方法 通过TCMSP、BATMAN-TCM数据库检索白虎汤的药物活性成分和靶点,通过GeneCards、NCBI、OMIM数据库检索急性肺损伤相关靶点,通过蛋白相互作用网络构建及GO、KEGG通路富集分析确定白虎汤治疗急性肺损伤的重要信号通路,对主要活性成分与核心靶点蛋白进行分子对接,通过动物实验观察白虎汤对急性肺损伤致死模型小鼠生存率及炎症因子含量的影响。结果 筛选得到白虎汤与急性肺损伤共同靶点211个,筛选出槲皮素、山柰酚、豆甾醇等主要活性成分。KEGG通路富集分析表明,白虎汤通过Toll样受体信号通路、NOD样受体信号通路、T细胞受体信号通路和MAPK信号通路等多种信号通路发挥其治疗急性肺损伤的药理作用。分子对接结果显示,白虎汤有效成分与MAPK14、STAT3、JUN、MAPK1、MAPK3、FOS、RELA有很好的结合能力。动物实验结果显示,与模型组比较,白虎汤组小鼠生存率显著升高,肺组织病理损伤程度减轻,血清白细胞介素-6、肿瘤坏死因子-α含量明显降低(P<0.05)。结论 白虎汤可通过减轻肺组织病理损伤和减少炎症因子释放有效治疗急性肺损伤。Objective To explore the mechanism of Baihu Decoction in the treatment of acute lung injury based on network pharmacology and molecular docking technology;To carry out experimental verification.Methods The active components and targets of Baihu Decoction were searched through TCMSP and BATMAN-TCM databases,and human gene searches were conducted in GeneCards,NCBI,and OMIM databases.PPI network construction and GO and KEGG pathway enrichment analysis were conducted to determine the important signaling pathways of Baihu Decoction and acute lung injury.Molecular docking of main active components and core target proteins was performed.The effects of Baihu Decoction on survival rate and inflammatory cytokine content in acute lung injury lethal model mice were observed through animal experiments.Results Totally 211 common targets for Baihu Decoction and acute lung injury were screened,and identified effective components such as quercetin,kaempferol,and stigmasterol,etc.Analysis of KEGG pathway enrichment indicated that Baihu Decoction exerted its pharmacological effects in acute lung injury through a variety of signal pathways, including Toll-like receptorsignaling pathway, NOD-like receptor signaling pathway, T cell receptor signaling pathway, and MAPK signalingpathway. Molecular docking results showed that Baihu Decoction had good binding strength with MAPK14, STAT3,JUN, MAPK1, MAPK3, FOS and RELA. The results of animal experiments showed that compared with the modelgroup, the survival rate of mice in the Baihu Decoction group was significantly increased, the degree ofpathological injury in the lung tissue was reduced, and serum IL-6, TNF-α contents decreased significantly (P<0.05).Conclusion Baihu Decoction can treat acute lung injury by reducing pathological injury to lung tissue and releasingof inflammatory factors.

关 键 词：白虎汤 急性肺损伤 网络药理学 实验验证 作用机制 

分 类 号：R259.63[医药卫生—中西医结合] R285[医药卫生—中医内科学]