OBJECTIVE To investigate the effect of Stachydrine (STA) on neuroinflammation in vascular dementia (VD) rats by regulating the CC chemokine ligand 2 (CCL2) - CC chemokine receptor 2 (CCR2) signaling pathway.
METHODS VD rat model was constructed using bilateral carotid artery occlusion surgery. The rats were separated into sham surgery group, VD group, low-dose STA group, medium-dose STA group, and high-dose STA group. Morris water maze experiment was applied to detect cognitive function of rats in each group. HE staining was applied to observe pathological changes in hippocampal tissue. Nissl staining was applied to observe neuronal damage in hippocampal tissue. Immunofluorescence was applied to observe the activation of microglia in hippocampal tissue. ELISA was applied to detect the levels of IL-6, TNF-α, and IL-8 in hippocampal tissue. Western blotting was applied to detect protein expression of IL-6, TNF-α, CCL2, and CCR2.
RESULTS Compared with the sham surgery group, the neurons in the hippocampus of rats in the VD group were disordered and damaged, the escape latency, number of Iba1 positive cells, levels of IL-6, TNF-α, IL-8, and expression of IL-6, TNF-α, CCL2, and CCR2 proteins obviously increased (P<0.05), the number of crossing platforms and the number of Nissl bodies obviously decreased (P<0.05); compared with the VD group, the hippocampal neurons in the low, medium, and high dose groups of STA were arranged neatly, and the neuronal cells recovered, the escape latency, number of Iba1 positive cells, levels of IL-6, TNF-α, IL-8, and expression of IL-6, TNF-α, CCL2, and CCR2 proteins obviously decreased (P<0.05), the number of crossing platforms and the number of Nissl bodies obviously increased (P<0.05), and the high-dose STA group had the most obvious improvement effect.
CONCLUSION STA can improve neuronal damage and reduce neuroinflammation in VD rats, which may be related to the inhibition of the CCL2-CCR2 signaling pathway.
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