摘要
目的研究柴胡桂枝汤(CGD)治疗流感继发细菌性肺炎的作用机制。方法建立流感继发细菌性肺炎模型,采用CGD进行干预,采用UPLC-Q-Exactive/MS技术对CGD成分进行定性分析。采用网络药理学方法挖掘CGD中成分的潜在作用靶点及流感继发细菌性肺炎相关靶点,构建“成分-靶点-疾病”网络。采用KEGG分析和GO分析富集核心作用通路。采用分子对接验证核心成分与关键靶点间的相互作用,RTqPCR对核心靶点进行验证。结果CGD能显著改善共感染引起的体重、胸腺指数(P<0.05)的下降;降低肺指数(P<0.05)、MmRNA的相对表达量(P<0.05)和细菌载量(P<0.05),提高生存率。从CGD中鉴定得到51个化学成分;网络药理学分析挖掘CGD治疗流感继发细菌性肺炎所对应的相关靶点107个,其中TNF、AKT1、ALB、VEGFA、MAPK3、PTGS2、STAT3、EGFR等靶点关联性较强,主要涉及Fc epsilon RI信号通路、GnRH信号通路、NF-κB信号通路等;通过分子对接研究显示CGD主要活性成分千层纸素A-7-O-β-D-葡萄糖醛酸苷、黄芩素、汉黄芩素与TNF、PTGS2、EGFR靶点有强亲和活性。与共感染模型组相比,CGD组TNF-α显著降低,EGFR、PTGS2显著升高(P<0.05)。结论CGD的主要活性成分千层纸素A-7-O-β-D-葡萄糖醛酸苷、黄芩素、汉黄芩素作用于TNF-α、PTGS2、EGFR等靶点,来发挥治疗流感-金黄色的葡萄球菌共感染的作用。
Objective To study the mechanism of Chaihu Guizhi Decoction(CGD)in the treatment of influenza and staphylococcus aureus co-infection.Methods The co-infection model of influenza and staphylococcus aureus was established and CGD was used to intervene.The chemical components of CGD were qualitatively analyzed by UPLC-QExactive/MS technology.The potential action targets of chemical components in CGD and the related targets of influenza Staphylococcus aureus co-infection were mined by network pharmacology method.The"component target disease"network was constructed.Core targets were selected according to degree ranking.Core action pathways were enriched by KEGG analysis and GO annotation analysis.The core target was verified by RT-qPCR,and the interaction between the core component and the key target was verified by molecular docking.Results CGD could significantly improve the decrease of body weight and thymus index(P<0.05)caused by co-infection.The lung index(P<0.05),relative amount of MmRNA expression(P<0.05)and bacterial load(P<0.05)were decreased,and the survival rate was improved.51 chemical constituents were identified from CGD.Through network pharmacological analysis,107 related targets corresponding to CGD treatment of bacterial pneumonia secondary to influenza were excavated.TNF,AKT1,ALB,VEGFA,MAPK3,PTGS2,STAT3,EGFR and other targets with strong correlation,mainly involved Fc epsilon RI signal pathway,GnRH signal pathway,NF-κB signal path,etc.Molecular docking study showed that the main active component of CGD,including oroxyloside,baicalein and wogonin have strong affinity with TNF,PTGS2 and EGFR targets.Compared with co-infection model group,in CGD group TNF-α、EGFR and PTGS2 increased significantly(P<0.05).Conclusion The main active ingredient of CGD is oroxyloside,baicalein and wogonin.TNF-α,PTGS2,EGFR and other targets to played a role in the treatment of influenza staphylococcus aureus co-infection.
作者
韩雨秀
张静
罗竣瑜
贾艳铤
许金珂
孙启慧
王旭
杨勇
容蓉
Han Yuxiu;Zhang Jing;Luo Junyu;Jia Yanting;Xu Jinke;Sun Qihui;Wang Xu;Yang Yong;Rong Rong(School of Medicine,Shandong University of Traditional Chinese Medicine,Jinan 250355,China;Shandong Provincial Center for Disease Control and Prevention,Jinan 250014,China;Experimental Center of Shandong University of Traditional Chinese Medicine,Jinan 250355,China;Key Laboratory of Classical Theory of Traditional Chinese Medicine,Ministry of Education,Jinan 250355,China;Basic Research of Traditional Chinese Medicine,Shandong Provincial Key Laboratory,Jinan 250355,China;Shandong Antivirus Engineering Research Center of Traditional Chinese Medicine,Jinan 250355,China)
出处
《世界科学技术-中医药现代化》
CSCD
北大核心
2023年第6期2111-2121,共11页
Modernization of Traditional Chinese Medicine and Materia Medica-World Science and Technology
基金
国家自然科学基金委员会面上项目(81873220):基于证-毒-效关联技术辨识麻黄细辛附子汤对心肌线粒体细胞色素C氧酶调控的非线性生物学靶向特征,负责人:容蓉
山东省自然科学基金委员会培育项目(ZR2021LZY012):中医药抗新型冠状病毒研究-基于靶点活性的抗新型冠状病毒药物成分/组分筛选,负责人:杨勇
山东省重点研发计划(重大科技创新工程)(2020CXGC010505):治疗呼吸道病毒性疾病的中药新药研发及其共性关键技术研究,负责人:容蓉。
