基于高通量质谱技术对糖尿病伴行为学异常小鼠模型的多组学分析及验证  

Multi-omics Analysis and Validation of a Mouse Model of Diabetes Mellitus with Behavioral Abnormalities Based on High-throughput Mass Spectrometry

作　　者：杨淑芳 张浩强 陈茜 范琳 余烨璠 王少华[2] YANG Shufang;ZHANG Haoqiang;CHEN Xi;FAN Lin;YU Yefan;WANG Shaohua(Department of Endocrinology,the Affiliated Taizhou People’s Hospital of Nanjing Medical University,Taizhou,Jiangsu,225300,China;Department of Endocrinology,Zhongda Hospital,Southeast University,Nanjing,210000,China;School of Medicine,Southeast University,Nanjing,210000,China;Department of Endocrinology,the First Affiliated Hospital of University of Science and Technology of China,Hefei,230001,China)

机构地区：[1]南京医科大学附属泰州人民医院内分泌科,江苏省泰州市225300 [2]东南大学附属中大医院内分泌科,南京市210000 [3]东南大学医学院,南京市210000 [4]中国科学技术大学附属第一医院内分泌科,合肥市230000

出　　处：《医学分子生物学杂志》2025年第2期131-138,共8页Journal of Medical Molecular Biology

基　　金：南京医科大学泰州临床医学院重点研究项(No.TZKY20230307);泰州市人民医院课题(No.ZL202219)。

摘　　要：目的通过高通量质谱方法筛选2型糖尿病伴认知行为异常小鼠模型中差异表达的蛋白及代谢物并进行验证。方法检测DB组(认知行为异常组)和M组(认知行为正常组)小鼠模型海马组织蛋白质及血清代谢物的表达,进行生物信息学分析,筛选目标蛋白质及代谢物并验证。结果①45个蛋白质和119个正离子及110个负离子代谢物差异显著,KEGG分析显示差异表达基因富集在多个代谢途径。②关联分析显示含血清素的神经突触和嘌呤代谢通路是多组学分析共同富集的通路。③丙酮酸激酶同工酶(pyruvate kinase L/R,PKLR)、花生四烯酸(arachidonic acid,AA)、单磷酸腺苷(adenosine 5′-monophosphate,AMP)有差异表达。结论PKLR和AA、AMP可能可以作为2型糖尿病伴认知功能障碍疾病诊断的潜在生物标志物。Objective To screen and verify the differentially expressed protein and the metabolites in a mouse model of type 2 diabetes mellitus with cognitive behavior abnormalities by highthroughput mass spectrometry.Methods High-throughput mass spectrometry was used to detect the levels of hippocampal tissue protein expression and serum metabolites in the DB group(abnormal cognitive behavior group)and the M group(normal cognitive behavior group).Target proteins and metabolites were screened out by bioinformatics and were then verified through Western blotting and ELISA.Results①45 proteins and 119 positive ion-and 110 negative ion-metabolites were found to be significantly expressed,and KEGG analysis showed that the differentially expressed genes were enriched in multiple metabolic pathways.②Correlation analysis showed that serotonin-containing synapses and purine metabolism pathways were pathways co-enriched by multi-omics analysis.③pyruvate kinase L/R(PKLR)、arachidonic acid(AA)and adenosine 5′-monophosphate,(AMP)were differentially expressed.Conclusion PKLR,AA and AMP may be used as potential biomarkers for the diagnosis of type 2 diabetes mellitus with cognitive dysfunction.

关 键 词：2型糖尿病 DB/DB小鼠 认知障碍 多组学 

分 类 号：R332[医药卫生—人体生理学]