To investigate the effects of Danggui Buxue Decoction (DBD) on the nuclear factor erythroid 2-related factor 2/glutathione peroxidase 4 pathway, degree of lipid peroxidation, and synaptic plasticity of rats with vascular dementia (VD) induced by bilateral common carotid artery ligation (2-VO).

Sixty male SPF grade SD rats were randomly divided into sham surgery group, bilateral common carotid artery ligation VD model group, low-dose 2-VO+DBD group, medium dose 2-VO+DBD group, high-dose 2-VO+DBD group, and 2-VO+donepezil group, with 10 rats in each group. After 24 hours of modeling, continuous administration was performed for 4 weeks and samples were collected. The Morris water maze experiment and the dark avoidance experiment were used to evaluate the influence on the learning and memory ability of rats. The lipid peroxidation level was detected using a kit, and the morphology of hippocampal neurons was observed using Nissl staining. The expression of hippocampal neurons was observed using immunofluorescence staining, and the expression of pathway and synaptic plasticity-related proteins was detected using Western blotting. The mitochondria and synaptic ultrastructures of hippocampal neurons were observed using transmission electron microscopy, and the morphology and density of dendritic spines of hippocampal neurons were observed using Golgi staining.

The Morris water maze experiment and the dark avoidance experiment demonstrated that DBD could enhance the learning and memory abilities of rats. The results of Nissl staining and immunofluorescence showed that after DBD administration, the number of hippocampal neurons in the VD model group of rats increased, the expression rate of Nrf2 increased, and the neuronal damage was improved. VD rats showed a decrease in GSH levels, an increase in lipid peroxide and 4-hydroxynonenal levels, and DBD administration could alleviate oxidative stress. In VD rats, the expression of NAD(P)H quinone dehydrogenase 1, GPX4, Nrf2, postsynaptic density protein 95, Synapsin1, and brain-derived neurotrophic factor proteins decreased, and all of these significantly increased after administration of high dose DBD. Transmission electron microscopy and Golgi staining showed that DBD could improve the mitochondrial structure and synaptic ultrastructure of neurons, and increase the density of dendritic spines.

DBD can exert a neuroprotective effect and improve the learning and memory abilities of VD model rats by regulating the Nrf2/GPX4 signaling pathway, inhibiting neuronal lipid peroxidation, and enhancing synaptic plasticity.