Abstract: 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 thelevels 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 andELISA. Results ① 45 proteins and 119 positive ion-and 110 negative ion-metabolites were found tobe significantly expressed, and KEGG analysis showed that the differentially expressed genes were enriched in multiple metabolic pathways. ② Correlation analysis showed that serotonin-containing synapses and purine metabolism pathways were pathways co-enriched by multi-omics analysis. ③ pyruvate kinase L / R ( PKLR )、 arachidonic acid ( AA ) and adenosine 5′-monophosphate, (AMP) were differentially expressed. Conclusion PKLR, AA and AMP may be used as potentialbiomarkers for the diagnosis of type 2 diabetes mellitus with cognitive dysfunction.

Key words: type 2 diabetes, db / db mice, cognitive impairment, multi-omics