Abstract: Objective To explore the patho-physiological changes of sleep deprivation (SD) by analyzing the urinary proteome and metabolome of sleep-deprived mouse models. Methods Twelve male mice were randomly divided into a control group and a model group with six in each. Urine samples were collected daily from metabolic cages for 8 consecutive days and subjected to liquid chromatography-mass spectrometry (LC-MS)-based proteomic and metabolomic analyses. Results A total of 855 differential proteins were identified in the urine of sleep-deprived mouse models. Function annotation analysis showed an enrichment in the complement and coagulation cascades and glutathione metabolism pathways. Additionally, 158 differential metabolites were identified, which were primarily enriched in metabolic pathways such as pigment metabolic processes, signal transduction/ regulation and immune response activation. Integrated proteomic and metabolomic analysis revealed that the core function pathways were glutathione metabolism and complement and coagulation cascades. Conclusions Changes in SD-related protein and metabolite metabolic pathways provide novel insights into the mechanisms underlying sleep deprivation.

Key words: sleep deprivation, proteomics, metabolomics, urine