酸枣仁汤调控慢性睡眠剥夺大鼠脑微区空间代谢网络作用研究OA

Objective To elucidate the mechanism by which Suanzaoren Decoction(SZRD)exerts its anti-insomnia and anxiolytic-like effects by in situ visualization of spatial metabolic networks in specific brain microregions of sleep-deprived rats,leveraging the data dimensionality reduction features of metabolomics and mass spectrometry imaging(MSI)technology.Methods A modified multiple-platform water environment rat model of sleep deprivation was established.The therapeutic efficacy of SZRD was evaluated using the elevated plus maze test and serum corticosterone levels.MSI technology was employed to observe the in situ expression and trends of small-molecule metabolites in the brains of sleep-deprived rats and to investigate the intervention characteristics of SZRD.Results After 21 days of sleep deprivation using the modified multiple-platform method,normal rats exhibited anxiety-like behaviors.Compared to the model group,SZRD significantly increased the time ratio and number of entries into the open arms(P<0.05),reduced serum corticosterone levels(P<0.01),and markedly ameliorated insomnia and anxiety-like behaviors in sleep-deprived rats.MSI results showed that chronic sleep deprivation significantly altered the levels of neurotransmitters and their metabolites in the hippocampus,hypothalamus,striatum,and cortex of rats.SZRD significantly modulated the levels of 34 differential metabolites in the brain,primarily including amino acids and their metabolites.Pathway analysis suggested that SZRD may exert its effects by regulating histidine metabolism,alanine,aspartate and glutamate metabolism,tryptophan metabolism,tyrosine metabolism,and arginine metabolism pathways.Conclusion SZRD exerts anti-insomnia and anxiolytic effects by regulating small-molecule amino acid metabolic pathways(such as tryptophan and tyrosine metabolism)and modulating the content and spatial distribution of neurotransmitters in the brain.These findings provide a scientific basis for the precise application and multi-target characteristics of SZRD in improving sleep disorders.