基于UPLC-MS技术探究糖脂代谢病的血清代谢谱特征  

Characteristics of the serum metabolic spectrum of glucolipid metabolic disease by UPLC⁃MS

作　　者：赵亚茹 韩怡 朴婧羽 罗朵生[1,2] ZHAO Yaru;HAN Yi;PIAO Jingyu;LUO Duosheng(Key Laboratory of Glucolipid Metabolic Diseases,Ministry of Education,Guangdong Pharmaceutical University,Guangzhou 510006,China;Guangdong Provincial TCM Key Laboratory for Metabolic Diseases,Guangdong Pharmaceutical University,Guangzhou 510006)

机构地区：[1]糖脂代谢病教育重点实验室,广东药科大学,广州510006 [2]广东省代谢性疾病中医药防治重点实验室,广东药科大学,广州510006

出　　处：《中国比较医学杂志》2023年第5期24-35,共12页Chinese Journal of Comparative Medicine

基　　金：国家自然科学基金项目(81830113,82074210);广东省重大基础及应用基础研究(2019B030302005)。

摘　　要：目的旨在分析非酒精性脂肪性肝病(non-alcoholic fatty liver disease,NAFLD)、2型糖尿病(type 2 diabetes mellitus,T2D)和动脉粥样硬化(atherosclerosis,AS)的血清代谢组学谱特征。方法分别建立NAFLD、T2D和AS小鼠模型,采用液质联用(ultra-high performance liquid chromatography-mass spectrometry,UPLC-MS)技术分析小鼠血清代谢谱,基于R语言MetaboAnalystR包分析数据,结合多元统计学方法筛选差异代谢物,通过非靶向KEGG富集分析获得差异代谢通路,最后将差异代谢物与血脂进行关联分析。结果NAFLD、T2D和AS共同拥有48种差异代谢物,主要富集在亚油酸代谢、磷酸戊糖代谢、花生四烯酸代谢和组氨酸代谢通路(P<0.05),且差异代谢物与血脂显著相关。与对照组相比,NAFLD、T2D和AS主要个性代谢通路分别为D-精氨酸和D-鸟氨酸代谢(P=0.09),半乳糖代谢、初级胆汁酸生物合成和淀粉和蔗糖代谢(P<0.05),鞘脂代谢和嘧啶代谢(P<0.05)。三种疾病两两相比,在D-精氨酸和D-鸟氨酸代谢(P=0.12)、淀粉和蔗糖代谢(P<0.01)、D-谷氨酰胺和D-谷氨酸代谢(P<0.05)、酮体的合成与降解(P=0.06)、鞘脂类代谢(P<0.05)、缬氨酸、亮氨酸和异亮氨酸的降解(P<0.05)、丙氨酸,天冬氨酸和谷氨酸代谢(P<0.05)和甘氨酸、丝氨酸、苏氨酸代谢(P=0.12)等通路存在差异。结论从代谢组学角度解析了NAFLD、T2D与AS的共性和个性特征,为上述疾病的综合防治和个性化治疗提供线索。Objective To analyze the serum metabolomics of non⁃alcoholic fatty liver disease(NAFLD),type 2 diabetes mellitus(T2D),and atherosclerosis(AS).Methods NAFLD,T2D,and AS mouse models were established,and serum metabolomics were analyzed by ultra⁃high performance liquid chromatography⁃mass spectrometry(UPLC⁃MS).Data were analyzed using the R language MetaboAnalystR package.Differential metabolites were screened by multivariate statistics.Differential metabolic pathways were obtained by untargeted KEGG enrichment analysis.The result were analyzed for correlations between differential metabolites and blood lipids.Results NAFLD,T2D and AS shared 48 differential metabolites that were particularly enriched in linoleic acid metabolism,pentose phosphate metabolism,arachidonic acid metabolism,and histidine metabolism pathways(P<0.05).The differential metabolites were significantly correlated to blood lipids.Compared with the control group,the main specific metabolic pathways of NAFLD,T2D and AS were D⁃arginine and D⁃ornithine metabolism(P=0.09),galactose metabolism,primary bile acid biosynthesis,starch,and sucrose metabolism(P<0.05),and sphingolipid and pyrimidine metabolism(P<0.05),respectively.The three diseases were compared pairwise,and there were differences in D⁃arginine and D⁃ornithine metabolism(P=0.12),starch and sucrose metabolism(P<0.01),D⁃glutamine and D⁃glutamate metabolism(P<0.05),synthesis and degradation of ketone bodies(P=0.06),alanine,aspartate and glutamate metabolism(P<0.05),sphingolipid metabolism(P<0.05),valine,leucine and isoleucine degradation(P<0.05),and glycine,serine,and threonine metabolism(P=0.12).Conclusions This study revealed the common and specific metabolic characteristics of NAFLD,T2D and AS,and provides for a research direction for comprehensive prevention and individualized treatment of these diseases.

关 键 词：非酒精性脂肪性肝病 2型糖尿病 动脉粥样硬化 UPLC-MS 代谢组学 

分 类 号：R-33[医药卫生]