目的:基于网络药理学和动物实验探讨葛根素对酒精性肝损伤(alcoholic liver disease，ALD)的作用机制。方法:利用数据库收集葛根素相关靶点及ALD相关基因靶点，绘制韦恩图得到交集靶点，并构建蛋白质互作网络和"药物-靶点-通路"网络图，筛选核心靶点，利用R语言软件将靶点进行基因本体(gene ontology，GO)功能分析和京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes，KEGG)富集分析预测葛根素治疗ALD的作用机制并建立动物模型进一步验证。结果:网络药理学分析得到葛根素治疗ALD的交集靶点199个，筛选得到AKT1、ALB、IL-6、TNF、IL-1β等45个核心靶点。GO注释分析得到2 668个生物过程信息、160个分子功能信息和34个细胞分子信息，KEGG分析涉及186条关键通路。动物实验表明，葛根素可以保护ALD小鼠的肝脏功能，改善氧化应激和脂质沉积，减少肝脏组织的炎症浸润，同时降低肝脏组织中肿瘤坏死因子-α(tumor necrosis factor-alpha，TNF-α)、核转录因子-κB(nuclear factor kappa-B，NF-κB)、核苷酸寡聚化结构域样受体家族3(NOD-like receptor protein 3，NLRP3)的蛋白表达(P＜0。05)。结论:葛根素可以通过改善氧化损伤、抑制炎症反应从而发挥治疗ALD的作用。
Mechanism of puerarin in protecting chronic alcoholic liver disease based upon network pharmacology and animal experiments
OBJECTIVE To explore the mechanism of puerarin for protecting alcoholic liver disease(ALD)based upon net-work pharmacology and animal experiments.METHODS The database was utilized for collecting puerarin/ALD-related gene targets and Venn diagram was plotted for obtaining the intersection targets.Protein interaction and"drug-target-pathway"net-works were constructed for screening the potential core targets.And gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses were performed for predicting the protective mechanism of puerarin against ALD.RESULTS Network pharmacological analyses yielded 199 intersecting targets of puerarin for antagonizing ALD and screening harvested 45 core targets,including AKT1,albumin(ALB),interleukin-6(IL-6),tumor necrosis factor-alpha(TNF-α)and interleukin-1β(IL-1β),etc.GO analysis yielded 2 668 biological process items,160 molecular function items and 34 cellular com-ponent items.KEGG analysis involved 186 key pathways.Animal experiments indicated that puerarin could protect liver function of ALD mice,improve oxidative stress and lipid deposition and reduce inflammatory infiltration of liver tissue.At the same time,the expressions of TNF-α,nuclear factor kappa-B(NF-κB)and NOD-like receptor protein 3(NLRP3)declined markedly in liver tissue(P＜0.05).CONCLUSION Puerarin may protect ALD through improving oxidative damage and stunting inflammatory reaction.
NETL
NSTL
万方数据
