Mechanism of cerebroprotein hydrolysate-1 improving cognitive impairment in vascular dementia rats
10.3969/j.issn.1009-0126.2025.09.027
- VernacularTitle:脑多肽改善血管性痴呆大鼠认知障碍的机制研究
- Author:
Qinying MA
1
;
Lixuan LI
1
;
Yanan REN
1
;
Bing LI
1
;
Huimin SHI
1
;
Jiyu FANG
1
Author Information
1. 050031 石家庄,河北医科大学第一医院神经内科河北省脑老化与认知神经科学实验室
- Publication Type:Journal Article
- Keywords:
autophagy;
dementia,vascular;
antioxidant response elements;
cerebroprotein hydroly-sate-1
- From:
Chinese Journal of Geriatric Heart Brain and Vessel Diseases
2025;27(9):1257-1262
- CountryChina
- Language:Chinese
-
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.