摘要
目的:应用代谢组学与网络药理学研究腹部推拿改善2型糖尿病(T2DM)临床症状及体征的手法效应机制。方法:高脂饲料联合链脲佐菌素建立威斯塔(Wistar)大鼠T2DM模型,运用简单随机化分为空白对照组、模型组和推拿组。模型组与推拿组大鼠持续高脂饲料喂养,推拿组每天给予腹部推拿1次,共计8周,分别记录第0、2、4、8周的FBG。收集各组大鼠血清与尿液,采用超高效液相色谱-四极杆-飞行时间质谱分析各组大鼠代谢轮廓变化,利用代谢组分析工具(Markerlynx)软件筛选差异代谢物,借助代谢分析(MetaboAnalyst)数据库查询相关代谢通路。运用网络药理学获取腹部推拿改善T2DM的关键靶点基因,利用细胞网络分析软件(Cytoscape)构建“差异成分-靶点-疾病”网络图,并对关键靶点基因进行基因本体(GO)富集分析和京都基因与基因组百科全书(KEGG)通路分析。结果:腹部推拿可显著改善T2DM大鼠的FBG,代谢组学筛选出L-谷氨酸、核黄素、亚油酸等15个差异代谢物,主要涉及亚油酸代谢、核黄素代谢等代谢通路。网络药理学预测腹部推拿改善T2DM的潜在靶点基因有135个,包括溶血磷脂酸受体1,3(LPAR1,3)、ATP-柠檬酸裂解酶(ACLY)、3-羟基-3-甲基戊二酰辅酶A还原酶(HMGCR)等潜在靶基因,主要富集在神经活性配体-受体相互作用、谷氨酸神经突触等信号通路上。结论:腹部推拿可有效改善T2DM大鼠的糖代谢,其手法效应或通过ACLY-HMGCR代谢轴及LPAR家族调节亚油酸、核黄素等代谢通路实现。
Objective:To investigate the mechanisms of manipulation effect of abdominal Tuina on clinical symptoms and signs of type 2 diabetes mellitus(T2DM)using metabolomics and network pharmacology.Methods:A T2DM model was established in Wistar rats by combining a high-fat diet with streptozotocin injection.Rats were randomly assigned to a control group,a model group,and a Tuina group.The model and Tuina groups continued on a high-fat diet,and the Tuina group received abdominal Tuina once daily for 8 weeks.Fasting blood glucose(FBG)was recorded at weeks 0,2,4,and 8.Serum and urine samples were collected for ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry(UHPLC-QTOF-MS)to profile metabolic changes.Differential metabolites were identified using Markerlynx software,and related metabolic pathways were analyzed using the MetaboAnalyst database.Network pharmacology was applied to identify key target genes of abdominal Tuina in T2DM.Cytoscape was used to construct a“differential metabolite-target-disease”network,and gene ontology(GO)enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analyses were performed for the key target genes.Results:Abdominal Tuina significantly improved FBG in T2DM rats.Metabolomics identified 15 differential metabolites,including L-glutamic acid,riboflavin,and linoleic acid,primarily involved in linoleic acid metabolism and riboflavin metabolism.Network pharmacology predicted 135 potential target genes,including lysophosphatidic acid receptors 1 and 3(LPAR1,LPAR3),ATP citrate lyase(ACLY),and 3-hydroxy-3-methylglutaryl-CoA reductase(HMGCR).These genes were mainly enriched in neuroactive ligand-receptor interaction,glutamatergic synapse,and related signaling pathways.Conclusion:Abdominal Tuina effectively improves glucose metabolism in T2DM rats.Its manipulation effect may involve regulation of linoleic acid and riboflavin metabolic pathways via the ACLY-HMGCR metabolic axis and LPAR family.
作者
钮妍
宋红志
温彬宇
国生
沈潜
魏培栋
蔡明亨
李岩琪
王泽中
王康
NIU Yan;SONG Hongzhi;WEN Binyu;GUO Sheng;SHEN Qian;WEI Peidong;CAI Mingheng;LI Yanqi;WANG Zezhong;WANG Kang(Beijing University of Chinese Medicine Third Affiliated Hospital,Beijing 100029,China;Dongfang Hospital,Beijing University of Chinese Medicine,Beijing 100071,China;Chinese Medical College of Tianjin University of Traditional Chinese Medicine,Tianjin 301617,China)
出处
《世界中医药》
北大核心
2025年第17期3062-3071,共10页
World Chinese Medicine
基金
国家自然科学基金项目(81574092)
北京市自然科学基金项目(7242223)。
