基于网络药理学与回顾性研究探索贞芪扶正颗粒提高机体免疫力的作用机制  

Molecular Mechanism of Zhenqi Fuzheng Keli in Improving Immunity:An Investigational Study Based on Network Pharmacology and Retrospective Analysis

作　　者：贾江松[1] 付中华[1] 李坤[1] 王锌[1] 张伟[1] JIA Jiang-song;FU Zhong-hua;LI Kun;WANG Xin;ZHANG Wei(Department of Pharmacy,Henan Provincial People's Hospital,Zhengzhou 450003,China)

机构地区：[1]河南省人民医院药学部,郑州450003

出　　处：《中国合理用药探索》2023年第7期124-130,共7页Chinese Journal of Rational Drug Use

基　　金：国家自然科学基金资助项目(81803357)。

摘　　要：目的:采用网络药理学方法和分子对接技术,结合临床病例回顾性分析,探讨贞芪扶正颗粒提高机体免疫力的作用机制。方法:利用中药系统药理学数据库与分析平台(TCMSP)、Uniprot、OMIM和GeneCards数据库检索贞芪扶正颗粒提高免疫力的主要活性成份和靶点。使用Cytoscape3.6.1软件、STRING数据库、DAVID数据库构建蛋白相互作用网络、基因本体(GO)和京都基因与基因组百科全书(KEGG)富集分析。借助SYBYL-X 2.0软件,对主要活性成份与基因靶点进行分子对接验证。回顾性选取某院2021年4~6月恶性实体肿瘤患者为研究对象,依据是否服用贞芪扶正颗粒分为观察组(n=66)与对照组(n=96),对两组一般资料及淋巴细胞免疫结果进行分析。结果:贞芪扶正颗粒有活性成份33个,涉及提高机体免疫基因靶点55个。富集分析得到487个GO条目和106条KEGG信号通路。网络拓扑分析得到主要活性成份与受体蛋白并进行分子对接验证,结果显示槲皮素、山柰酚、木犀草素等配体与TNF、IL6、TP53、AKT1基因受体蛋白结合性能均良好。淋巴细胞免疫分析结果显示,观察组的淋巴细胞、CD3+、NK、CD4^(+)绝对数目以及CD4^(+)百分比、CD4^(+)/CD8^(+)高于对照组,CD8^(+)百分比低于对照组(P<0.05)。结论:贞芪扶正颗粒可能通过多组份、多靶点参与多种生物学进程,增加机体淋巴细胞数量,调节免疫平衡,提高免疫力。Objective:To explore the molecular mechanism of Zhenqi Fuzheng Keli in improving immunity by means of network pharmacology and molecular docking plus retrospective analysis of clinical cases.Methods:TCMSP,Uniprot,OMIM and GeneCards databases were searched for the main active ingredients and targets of Zhenqi Fuzheng Keli involved in immunity improvement.A protein-protein interaction network was constructed using Cytoscape software 3.6.1,STRING database and DAVID database to perform an enrichment analysis of gene ontology(GO)and Kyoto encyclopedia of genes and genomes(KEEG).SYBYL-X(2.0)software was used to verify the molecular docking between the main active ingredients and the gene targets.Patients with solid malignancies treated in a certain hospital between April to June 2021 were retrospectively selected as the study population and divided into an observation group(n=66)and a control group(n=96)according to whether or not they took Zhengi Fuzheng keli.The general data and lymphocyte immunoassay results of the two groups were analyzed.Results:Totally 33 active ingredients and 55 immune gene targets were identified for Zhenqi Fuzheng Keli.Enrichment analysis yielded 487 GO entries and 106 KEGG signaling pathways.Network topology analysis showed that the ligands of quercetin,kaempferol and luteolin had good binding properties to TNF,IL6,TP53 and AKT1 receptor proteins.The results of lymphocyte immunoassay showed that compared with the control group,the observation group had higher absolute lymphocyte,CD3+and NK cell counts,a higher percentage of CD4^(+),a higher CD4^(+)/CD8^(+)ratio,and a lower percentage of CD8^(+)(P<0.05).Conclusion:This study reveals that Zhenqi Fuzheng Keli possibly improves immunity by participating in multiple biological processes through multi-component and multitarget mechanisms to increase the number of lymphocytes in the body and modulate the immune balance.

关 键 词：网络药理学 分子对接 贞芪扶正颗粒 免疫力 作用机制 

分 类 号：R285[医药卫生—中药学]