麻杏石甘汤调控FoxO信号通路治疗呼吸道合胞病毒感染作用机制探析:基于多数据库联合

Exploration of the Mechanism of Maxing Shigan Decoction Regulating FoxO Signaling Pathway in Treating Respiratory Syncytial Virus Infection by Combination of Multiple Databases

目的:明确叉头框蛋白O(FoxO)在呼吸道合胞病毒(RSV)感染疾病中的表达及意义,探究麻杏石甘汤是否通过调控FoxO信号通路治疗RSV感染疾病。方法:从基因数据存储的公共平台获得RSV感染人支气管上皮细胞(BEAS-2B细胞)差异表达基因(DEGs)微阵列数据集GSE6802、GSE3397,通过STRING网站联合Cytoscape可视化分析构建DEGs蛋白质互作(PPI)网络,根据蛋白质关联度筛选核心DEGs;通过DAVID数据平台进行核心DEGs的GO和KEGG富集分析;通过细胞实验验证麻杏石甘汤干预对RSV感染后BEAS-2B细胞FoxO信号通路及相关核心DEGs的影响。结果:基于微阵列数据库联合PPI网络筛选出60个核心DEGs,KEGG分析显示FoxO信号通路差异性最为显著,富集该通路的核心DEGs:PLK3、ATG8、Gadd45A、Gadd45B和Bcl-6的生物学功能涉及细胞周期、细胞凋亡、免疫应答和氧化应激反应。细胞实验结果显示,麻杏石甘汤能够抑制RSV感染BEAS-2B细胞FoxO亚型FoxO1、FoxO3、FoxO4、FoxO6转录水平,伴随富集于该通路的Bcl-6、ATG8、Gadd45A、PLK3、SGK1表达下调。结论:BEAS-2B细胞内FoxO信号激活可能是RSV感染致病的关键病机,而麻杏石甘汤能够通过靶向FoxO信号治疗RSV感染疾病。

Objective:To clarify the expression and significance of Forkhead box protein O(FoxO)in respiratory syncytial virus(RSV)infection diseases.To explore whether Maxing Shigan Decoction treats RSV infection diseases by regulating FoxO signaling pathway.Methods:Differentially expressed genes(DEGs)in human bronchial epithelial cells(BEAS-2B cell)infected with RSV were obtained from gene microarray datasets GSE6802 and GSE3397 uploaded on Gene Expression Omnibus platform.Core DEGs screened based on their protein correlation degrees were selected after constructing visualized protein-protein interaction(PPI)network through STRING website;GO and KEGG enrichment analysis of core DEGs were made on the DAVID data platform;Cell experiments were conducted to verify the effect of Maxing Shigan Decoction on transcription levels of FoxOs and related core DEGs in RSV-infected BEAS-2B cells infected with.Results:Based on the gene microarray datasets combined with PPI network,60 core DEGs were screened.FoxO signaling pathway showed the most significant difference pathway in KEGG enrichment analysis,and core DEGs including PLK3,ATG8,Gadd45A,Gadd45B,Bcl-6 were related with this pathway,involving in biological functions such as cell cycle,apoptosis,immune response,and oxidative stress.Cell experiments suggested that Maxing Shigan Decoction inhibited the transcription levels of FoxO subtypes FoxO1,FoxO3,FoxO4,and FoxO6 in RSV-infected BEAS-2B cells,accompanied by the downregulation of Bcl-6,ATG8,Gadd45A,PLK3 and SGK1.Conclusion:The activation of FoxOs in BEAS-2B cell may be a key pathogenesis of RSV infection,and Maxing Shigan Decoction may treat RSV infection diseases by targeting FoxO signaling pathway.