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基于高脂饮食对小鼠脾脏代谢组的影响探讨脾为之卫的内在机制

Exploring the intrinsic mechanism of"spleen as the guardian"based on the effects of high-fat diet on spleen metabolome in mice
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摘要 目的分析高脂饮食对小鼠脾脏代谢组学影响,探讨“脾为之卫”理论的科学内涵。方法将C57BL/6J小鼠随机分为正常对照(NFD)组和高脂饮食(HFD)组,分别给予普通饲料或高脂饲料喂养8周。检测小鼠体质量、脾脏质量,计算脾脏指数;采用生化法检测血脂含量;采用酶联免疫吸附法(ELISA)测定肿瘤坏死因子α(TNF-α)、白细胞介素6(IL-6)及白细胞介素1β(IL-1β)等炎症因子含量;通过非靶代谢组学技术检测小鼠脾脏代谢物,结合主成分分析和正交最小偏二乘判别分析筛选差异代谢物,利用KEGG及PubChem等数据库对差异代谢物进行富集分析。结果与NFD组相比,HFD组小鼠体质量、脾脏质量、血脂含量(TC、TG、HDL-C)和炎症因子含量(TNF-α、IL-6及IL-1β)均升高(P<0.05或P<0.01)。两组小鼠脾脏共有247种差异代谢物(P<0.05),其中有9种差异代谢物呈上升趋势,238种代谢物呈下降趋势,富集差异代谢物得到苯丙氨酸、酪氨酸和色氨酸的生物合成、D-谷氨酰胺和D-谷氨酸代谢、嘧啶代谢等34条代谢途径。结论高脂饮食可能通过干扰脾脏中氨基酸、嘧啶、脂肪酸等代谢,促发机体炎症和免疫反应。苯丙氨酸、酪氨酸和色氨酸生物合成、D-谷氨酰胺和D-谷氨酸代谢、嘧啶代谢、泛酸和辅酶A生物合成或是“脾为之卫”的关键物质基础。 Objective To analyze the effects of high-fat diet on spleen metabolomics in mice and explore the scientific connotation of the"spleen as the guardian"theory.Methods C57BL/6J mice were randomly divided into the normal control(NFD)group and high-fat diet(HFD)group,fed with standard chow and high-fat chow respectively for 8 weeks.Body mass,spleen mass,and spleen index were measured.Blood lipid levels were detected using the biochemical assays.Enzyme-linked immunosorbent assay(ELISA)was used to determine the contents of inflammatory factors including tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),and interleukin-1β(IL-1β).Non-targeted metabolomics technology was employed to detect spleen metabolites.Differential metabolites were screened through principal component analysis(PCA)and orthogonal partial least squares discriminant analysis(OPLS-DA),followed by enrichment analysis using KECG and PubChem databases.Results Compared with the NFD group,the HFD group showed increased body mass,spleen mass,blood lipid levels(TC,TG,HDL-C),and inflammatory factor levels(TNF-α,IL-6,IL-1β)(P<0.05 or P<0.01).A total of 247 differential metabolites(P<0.05)were identified in the spleen between the two groups,with 9 metabolites up-regulated and 238 down-regulated.Enrichment analysis revealed 34 metabolic pathways,including biosynthesis of phenylalanine,tyrosine and tryptophan,D-glutamine and D-glutamate metabolism,pyrimidine metabolism.Conclusion High-fat diet may trigger systemic inflammation and immune responses by interfering with amino acid,pyrimidine,and faty acid metabolism in the spleen.The biosynthesis of phenylalanine,tyrosine,and tryptophan;D-glutamine and D-glutamate metabolism;pyrimidine metabolism;and pantothenate and CoA biosynthesis may serve as the key material basis for the theory of"spleen as the guardian".
作者 白雪 廖颖 康洁 张凌媛 丁珊珊 BAI Xue;LIAO Ying;KANG Jie;ZHANG Lingyuan;DING Shanshan(Fujian University of Traditional Chinese Medicine,Fuzhou 350122,China)
机构地区 福建中医药大学
出处 《时珍国医国药》 北大核心 2025年第12期2378-2383,共6页 Lishizhen Medicine and Materia Medica Research
基金 福建省自然科学基金(2024J01133) 国家自然科学基金(82474391)。
关键词 高脂饮食 脾脏 代谢 免疫 脾为之卫 High-fat diet Spleen Metabolism Immunity Spleen as the guardian
作者简介 白雪(2000-),女(汉族),陕西宝鸡人,福建中医药大学在读硕士研究生,主要从事中医证的基础研究工作;通讯作者:丁珊珊(1987-),女(回族),福建晋江人,福建中医药大学副研究员,博士学位,主要从事中医证的基础研究工作.
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