【摘要】 目的 基于网络药理学探讨利拉鲁肽治疗阿尔茨海默病(AD)的相关作用靶点及主要信号通路。方法 通过SuperPred检索利拉鲁肽的靶点,通过利用GeneCards和OMIM数据库检索阿尔茨海默病的基因靶点,将疾病靶点与药物作用靶点融合。在String平台利用利拉鲁肽的靶标基因与AD靶标基因的交集基因构建蛋白相互作用,运用Cytoscape 3.8.2软件构建“利拉鲁肽-成分-靶点”网络,通过Metascape等数据库进行GO分析和KEGG富集分析。选用8月龄SAMP8小鼠连续皮下注射给药2个月后进行相关指标检测。采用免疫荧光法检测小鼠海马β淀粉样蛋白和丝裂原活化蛋白激酶的表达。结果 获得利拉鲁肽与AD的交集靶点基因共有131个,其中STAT3、HSP90AA1、CASP3、NFKB1、PTGS2、BCL2L1、MAPK1、ABL1、MCL1和CASP1为核心靶点。通过动物实验验证模型组小鼠Aβ、MAPK的蛋白表达低于对照组,利拉鲁肽组Aβ、MAPK的蛋白表达高于模型组。结论 基于网络药理学和动物实验验证MAPK信号通路是利拉鲁肽治疗AD的潜在靶点。更多还原

【Abstract】 Objective To explore the relevant target genes and main signaling pathways of Liraglutide in the treatment of Alzheimer’s disease(AD) based on network pharmacology. Methods The targets of Liraglutide were retrieved through SuperPred, and the gene targets of Alzheimer’s disease were retrieved by using the GeneCards and OMIM databases, fusing the disease targets with the drug action targets. Protein interactions were constructed using the intersection genes of Liraglutide target genes and AD target genes on the String platform. The "Liraglupeptide-component-target" network was constructed using Cytoscape 3.8.2 software, and GO analysis and KEGG enrichment analysis were conducted through databases such as Metascape. The relevant indicators of 8-month-old SAMP8 mice were detected after continuous subcutaneous injection for 2 months. The expressions of β-amyloid protein and mitogen-activated protein kinase in the hippocampus of mice were detected by immunofluorescence. Results A total of 131 intersection target genes between Liraglutide and AD were obtained,STAT3, HSP90 AA1, CASP3, NFKB1, PTGS2, BCL2L1, MAPK1, ABL1, MCL1 and CASP1 were the core targets. The animal experiments verified that the protein expression of Aβ and MAPK in the model group mice were lower than that in the control group, the protein expression of Aβ and MAPK in the Liraglutide group were higher than that in the model group. Conclusion Based on network pharmacology and animal experiments, the MAPK signaling pathway is a potential target for Liraglutide in the treatment of AD.更多还原