新葛根芩连汤调控NF-κB通路改善AD小鼠神经炎症的机制研究OA

Objective:To explore the effects of Xingegen Qinlian decoction on NF-κB pathway and related neu-roinflammatory molecules in APP/PS1 mice.Methods:APP/PS1 mice were randomly divided into model group,Xingegen Qinlian decoction group,and Donepezil Hydrochloride group.Age-and strain-matched C57 BL/6 mice were used as the control group.Behavioral changes were recorded after grouping interventions.After 90 days of interven-tion,the following assessments were conducted:the Morris water maze test to evaluate learning and memory abili-ties,Nissl staining to observe neuronal morphology in the hippocampus,Lead-uranium electron microscopy to observe ultrastructure of cells in the hippocampal region,Western blot to detect nuclear factor kappa-B(NF-κB)protein ex-pression,and ELISA to measure serum levels of phosphorylated tau protein(p-tau),interleukin-6(IL-6),and inter-leukin-1β(IL-1β).Results:Compared with the control group,the model group showed significantly prolonged escape latency(P<0.05);ill-defined hippocampal neuronal structures with extensive vacuoles and gliosis;nucleus nuclear membrane folds were obvious in neuronal intracellular bodies,mitochondria showed a large number of vacuole-like,e-lectron-dense fiber tangles were visible,presynaptic and post-synaptic membranes were blurred,and synaptic vesicles were significantly reduced.Increased NF-κB protein expression,and elevated serum levels of p-tau,IL-6,and IL-1β(P<0.05).Compared with the model group,all drug intervention groups exhibited shorter escape latency,with sta-tistically significant differences on days 3 and 5 of training(P<0.05).Most hippocampal neurons displayed clearer structures and orderly arrangements,with reduced gliosis.The mitochondria in the cytosol were basically intact,the organelles were uniformly distributed,scattered fibers were occasionally seen in the cytosol,the area of fiber entangle-ment was narrowed,the synaptic structure was clearer,and the synaptic vesicles were more densely packed.NF-κB protein expression in the hippocampus decreased,and serum p-tau levels declined,particularly in the Xingegen Qinlian decoction group(P<0.01).The Xingegen Qinlian decoction group also showed a more pronounced reduction in IL-1βlev-els compared to the Donepezil Hydrochloride group(P<0.01).Conclusion:The improvement of cognitive function by Xingegen Qinlian decoction group was associated with reduced neuroinflammation and decreased tau protein phos-phorylation,and the inhibition of NF-κB activity may be involved in this process.