基于代谢-转录组学的阻塞性睡眠呼吸暂停代谢特征和分子机制研究  

A Comprehensive Study on the Metabolic Characteristics and Molecular Mechanisms of Obstructive Sleep Apnea Syndrome Based on Metabolomics and Transcriptomics

作　　者：甘考[1,2] 高明 王炜烨 吴苑 李际强 陈剑坤[1,4] GAN Kao;GAO Ming;WANG Weiye;WU Yuan;LI Jiqiang;CHEN Jiankun(The Second Clinical Medical College,Guangzhou University of Chinese Medicine,Guangzhou,Guangdong 510006,P.R.China;The Emergency Department,The Second Affiliated Hospital of Guangzhou University of Chinese Medicine(Guangdong Provincial Hospital of Chinese Medicine),Guangzhou,Guangdong 510006,P.R.China;The Emergency Department,Nanhai District Hospital of Chinese Medicine(Guangdong Provincial Hospital of Integrated Chinese and Western Medicine),Guangdong 528000,P.R.China;The Third General Department,The Second Affiliated Hospital of Guangzhou University of Chinese Medicine(Guangdong Provincia Hospital of Chinese Medicine),Guangzhou,Guangdong 510006,P.R.China)

机构地区：[1]广州中医药大学第二临床医学院,广东广州510006 [2]广州中医药大学第二附属医院(广东省中医院)急诊科,广东广州510006 [3]广东省佛山市南海区中医院(广东省中西医结合医院)急诊科,广东佛山528200 [4]广州中医药大学第二附属医院(广东省中医院)综合三科,广东广州510006

出　　处：《中国呼吸与危重监护杂志》2025年第2期97-106,共10页Chinese Journal of Respiratory and Critical Care Medicine

基　　金：广州市科技计划–市校(院)联合资助基础与应用基础研究项目(2023A03J0227);广东省中医药局科研项目(20225020);广东省中医院朝阳人才科研专项(ZY2022YL04)。

摘　　要：目的本研究旨在探讨阻塞性睡眠呼吸暂停(Obstructive Sleep Apnea,OSA)患者外周血代谢物和转录组的变化,并评估其作为生物标志物的诊断价值。方法本研究利用液相色谱-质谱脂质靶向代谢组学技术,比较30例OSA患者与30例健康对照者的代谢轮廓,筛选出差异脂质代谢物。通过基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)富集分析,确定甘油脂代谢通路为显著差异代谢通路。进一步对6例OSA患者和6例健康对照者的外周血单核细胞(Peripheral Blood Mononuclear Cells,PBMC)进行转录组学分析,评估了相关通路分子的表达情况。结果共筛选出168种差异脂质代谢物,其中甘油脂代谢通路在OSA患者与健康对照者间具有显著差异。转录组学分析显示,甘油脂代谢相关基因GPAT、AGPAT和LPIN在OSA患者PBMC中低表达,提示甘油脂代谢通路在OSA患者中处于抑制状态。此外,诊断价值分析显示,GPAT和AGPAT具有较高的AUC值,可作为OSA的潜在生物标志物。结论甘油脂代谢通路的抑制与OSA的发生发展密切相关,且该通路中的关键基因GPAT、AGPAT和LPIN的低表达可能参与OSA的病理生理过程。这些发现不仅为理解OSA的发病机制提供了新的视角,也为从甘油脂代谢调控角度治疗OSA提供了新的科学依据。Objective The aim of this study was to investigate the changes in peripheral blood metabolites and transcriptomes in patients with obstructive sleep apnea(OSA)and to assess their diagnostic value as biomarkers.Methods In this study,we utilized liquid chromatography-tandem mass spectrometry(LC-MS/MS)lipid-targeted metabolomics to compare the metabolic profiles of 30 OSA patients with those of 30 healthy controls,identifying differential lipid metabolites.Through Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis,we determined that the glycerolipid metabolism pathway was significantly different.Furthermore,we conducted transcriptome analysis on peripheral blood mononuclear cells(PBMCs)from six OSA patients and six healthy controls to evaluate the expression of molecules related to the pathway.Results A total of 168 differential lipid metabolites were identified,with significant differences in the glycerolipid metabolism pathway between OSA patients and healthy controls.Transcriptome analysis revealed that glycerolipid metabolism-related molecules GPAT,AGPAT,and LPIN were under expressed in OSA patient PBMCs,suggesting that the glycerolipid metabolism pathway is suppressed in OSA patients.Additionally,diagnostic value analysis showed that GPAT and AGPAT had high AUC values,indicating their potential as biomarkers for OSA.Conclusion The suppression of the glycerolipid metabolism pathway is closely related to the development of OSA,and the under expression of key genes in this pathway,such as GPAT,AGPAT,and LPIN,may be involved in the pathophysiological process of OSA.These findings not only provide a new perspective for understanding the pathogenesis of OSA but also offer new scientific evidence for the treatment of OSA from the perspective of glycerolipid metabolism regulation.

关 键 词：阻塞性睡眠呼吸暂停 脂质组学 转录组学 甘油脂代谢 

分 类 号：R766[医药卫生—耳鼻咽喉科]