颈动脉粥样硬化差异基因筛选及小檗碱干预颈动脉粥样硬化机制的生物信息学研究

目的以生物信息学方法探讨颈动脉粥样硬化发病新的潜在机制,挖掘小檗碱干预颈动脉粥样硬化的潜在靶点和途径。方法检索获取美国国家生物技术信息中心基因表达综合数据库并获取颈动脉粥样硬化斑块基因表达芯片GSE28829数据集,筛选样本差异表达基因数据并进行富集分析;检索获取小檗碱的潜在作用靶点,与颈动脉粥样硬化差异表达基因取交集,获得小檗碱干预颈动脉粥样硬化的潜在靶点,进行富集分析并筛选核心靶点。结果共筛选获得颈动脉粥样硬化差异表达基因174个,涉及趋化因子、核因子κB、Toll样受体、脂肪酸降解等信号通路。筛选获得小檗碱干预颈动脉粥样硬化的潜在靶点5个,涉及流体剪切力与动脉硬化、白细胞介素17、肿瘤坏死因子等信号通路,经拓扑及富集分析,CCL2、HMOX1和MMP-9可能是小檗碱干预颈动脉粥样硬化的核心靶点。结论颈动脉粥样硬化差异表达基因主要富集于炎性反应、脂质代谢等信号通路;小檗碱可能通过介导CCL2、HMOX1、MMP-9等靶点调控流体剪切力、白细胞介素17、肿瘤坏死因子等信号通路而干预颈动脉粥样硬化。

The bioinformatics research of differentia gene expression in carotid atherosclerosis and potential mechanism of berberine intervening carotid atherosclerosis

Aim To investigate the new potential mechanisms of carotid atherosclerosis pathogenesis and explore the potential targets and pathways of berberine intervention in carotid atherosclerosis by bioinformatic research.Methods The study searched the Gene Expression Omnibus database of the National Center for Biotechnology Information(NCBI)and obtained the GSE28829 datasets of carotid atherosclerosis plaque gene expression microarray,screened the sample differentially expressed gene data for enrichment analysis.The potential targets of berberine were searched and obtained to be intersected with the differentially expressed genes of carotid atherosclerosis in order to obtain the potential targets of berberine intervention in carotid atherosclerosis.Enrichment analysis was performed and the core targets were screened.Results A total of 174 differentially expressed genes in carotid atherosclerosis were screened,involving chemokines,nuclear factor kappa B,Toll-like receptors,fatty acid degradation and other signaling pathways.Five potential targets of berberine in carotid atherosclerosis were screened,involving fluid shear and atherosclerosis,interleukin-17,tumor necrosis factor and other signaling pathways.Monocyte chemoattractant protein-1(MCP-1/CCL2),heme oxygenase 1(HO-1/HMOX1)and matrix metalloproteinase-9(MMP-9)were identified as the core targets of berberine intervening carotid atherosclerosis by topology and enrichment analysis.Conclusions Differentially expressed genes in carotid atherosclerosis are mainly enriched in signaling pathways such as inflammatory response and lipid metabolism;berberine may intervene in carotid atherosclerosis by mediating targets such as CCL2,HMOX1,MMP-9,and regulating fluid shear and atherosclerosis,interleukin-17,and tumor necrosis factor and other signaling pathways.