Mechanism of cerebroprotein hydrolysate-1 improving cognitive impairment in vascular dementia rats
Ma Qinying
Li Lixuan
Ren Yanan
Li Bing
Shi Huimin
Fang Jiyu
Abstract：Objective To explore the molecular mechanism of cerebroprotein hydrolysate-1(CH-1)in improving cognitive impairment of VD at animal level,and to determine the regulatory effect of CH-1 on Nrf2/ARE signaling pathway.Methods Thirty-six SD rats were randomly divided into sham operation group,VD group,low-and high-dose groups,with 9 rats in each group.VD model was established by bilateral common carotid artery ligation,and CH-1 was injected intraperitone-ally for 3 weeks.Morris water maze test and new object recognition test were performed to evalu-ate cognitive function.Hippocampal tissues was collected for immunohistochemistry/Western blot analysis.Results Compared with the sham operation group,the VD group exhibited significantly prolonged escape latency at 2-4 d of Morris water maze test,and up-regulated expression of ubiquitinated protein,LC3 Ⅱ/Ⅰ ratio,P65 and Beclin1 protein in the hippocampus,while down-regulated P62 expression(P＜0.05).Obviously shortened escape latency was observed in the high-dose group at 3-4 d and the low-dose group at 4 d than the VD group(P＜0.05).The resi-dence time in target quadrant,number of platform crossings,total exploration time of novel object recognition in the high-dose group and the total exploration time of novel object recognition in the low-dose group were significantly longer than those in VD group(P＜0.05).The expression levels of ubiquitinated,LC3 Ⅱ/Ⅰ ratio,P65 and Beclin1 were significantly lower in the low-dose group and high-dose group than the VD group(P＜0.05).The expression level of P62 protein in the VD group,low-and high-dose group were significantly increased in a dose-dependent manner(2.78±0.44,1.80±0.24 vs 3.67±0.34;2.37±0.26,1.53±0.09 vs 2.92±0.19;2.74±0.14,1.81±0.19 vs 3.93±0.50;2.28±0.17,1.72±0.17 vs 3.17±0.31,P＜0.05).Conclusion CH-1 can effectively improve the cognitive ability of VD rats and reduce the autophagy of hippocampal neurons.This therapeutic effect may be closely related to its enhancing activity of Nrf2/ARE signaling pathway.
Keywords：autophagydementiavascularantioxidant response elementscerebroprotein hydroly-sate-1
Publication Date：2025-09-15
Online Publishing Date：2025-09-29(First online date of this platform, not the publication date of the document)
Pages：6( 1257-1262 )