Effects of remimazolam on postoperative cognitive function in aging model rats via regulation of the BDNF/TrkB signaling pathway
10.12007/j.issn.0258-4646.2025.09.003
- VernacularTitle:瑞马唑仑通过调控BDNF/TrkB信号通路影响衰老大鼠模型术后认知功能
- Author:
Zhen WU
1
;
Xiaoyu MA
Author Information
1. 河北医科大学第四医院麻醉科,石家庄 050000
- Publication Type:Journal Article
- Keywords:
remimazolam;
brain-derived neurotrophic factor/tyrosine kinase receptor B;
aging;
postoperative cognitive function
- From:
Journal of China Medical University
2025;54(9):781-785
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the effects of remimazolam(Rem)on postoperative cognitive function in aging model rats and elu-cidate the mechanisms underlying its regulation of the brain-derived neurotrophic factor/tyrosine kinase receptor-B(BDNF/TrkB)pathway.Methods SD rats were randomly assigned to control,model,Rem-L,Rem-M,Rem-H,and Rem-H+7,8-DHF groups,and a Morris water maze test was used to evaluate the learning and memory abilities of rats,whereas pathological changes in the hippocampal neurons of rats were assessed histologically using hematoxylin and eosin staining.In addition,we also examined the levels of inflammatory factors,including interleukin-18(IL-18),tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β)in rat serum,and those of oxidative stress indi-cators[superoxide dismutase(SOD),glutathione peroxidase(GSH-PX),and malondialdehyde(MDA)]in brain tissue,whereas Western blotting analysis was performed to determine the expression of BDNF/TrkB signaling axis-related proteins and their downstream signaling molecules.Results Hippocampal neurons of the control group rats were observed to be characterized by a tight and regular arrangement,with clear cell boundaries,cytoplasm,and nuclei.Contrastingly,the hippocampal neurons of model group rats were found to be disorderly arranged,with irregular cell morphologies and condensed nuclei being detected in some cells.In water maze tests,compared with the con-trol group rats,those in the model group were found to have a longer escape latency(P＜0.05),and in these rats,we detected significant increases in the levels of IL-1β,IL-18,TNF-α in serum,and levels of MDA,BDNF,TrkB,p-AKT/AKT,and ERK1 in brain tissues(P＜0.05),whereas there were significant reductions in the levels of SOD and GSH(P＜0.05).Furthermore,compared with rats in the model group,the hippocampal neuronal cells of rats in the Rem-L,Rem-M,and Rem-H groups tended to become gradually more orderly,along with a progressive reduction in the number of damaged cells(P＜0.05).In addition,there was a gradual shortening of the escape latency of these rats(P＜0.05),along with gradual reductions in the levels of IL-1β,IL-18,TNF-α in serum,and the levels of MDA,BDNF,and TrkB in brain tissues(P＜0.05),whereas the levels of SOD and GSH gradually increased(P＜0.05).Moreover,we established that the addition of the BDNF/TrkB activator 7,8-DHF reversed the regulatory effect of Rem on the postoperative cognitive function in aging rats(P＜0.05).Conclusion Rem can regulate the postoperative cognitive function in aging rats,the underlying mechanisms of action of which may be associated with an inhibition of the BDNF/TrkB pathway.
