海南医科大学学报2025，Vol.31Issue(22)：1718-1728,11.DOI:10.13210/j.cnki.jhmu.20250115.002
血塞通软胶囊对东莨菪碱致阿尔茨海默病模型小鼠学习记忆能力及突触可塑性的影响研究
Effect of Xuesaitong soft capsule on learning memory ability and synaptic plasticity in mice with scopolamine-induced Alzheimer's disease model
摘要
Abstract
Objective:To investigate the effects of Xuesaitong soft capsule(XST)on the cognitive functions of scopolamine-induced Alzheimer's disease in mice and the modulation of synaptic plasticity.Methods:A total of 90 male Kunming mice were randomly divided into the blank(Control)group,the model(Model)group,the donepezil hydrochloride(DPH)group,and the Xuesaitong low,medium,and high dosage(XST-L,XST-M,XST-H)groups.The Alzheimer's disease model was prepared by intraperitoneal injection of scopolamine,and the spatial cognitive memory function of mice was detected by Mor-ris water maze.Hemoxylin-eosin staining(H&E)was used to observe the morphological changes in the CA1 and cortical areas of the mouse hippocampus.Transmission electron microscopy was used to observe ultrastructural changes in the hippocampus.ELI-SA was used to determine changes in the content of cyclic adenosine monophosphate(cAMP)in brain tissue.Immunohistochemi-cal staining was used to detect the expression levels of synaptophysin(SYN),growth-associated protein-43(GAP-43),and post-synaptic densifier-95(PSD-95)proteins.Western blot was performed to detect the expression of PSD-95,GAP-43,SYN,cyclic-AMP response binding protein(CREB),and protein kinase A(PKA)in the hippocampus and cortical regions.Results:The results of Morris water maze showed that compared to the Control group,the mice in the Model group had a significantly lon-ger mean escape latency,showed a decrease in the number of traversing platforms(P<0.05),and had lengthy and disorganised swimming trajectories.Compared to the Model group,the average escape latency of mice treated with XST was significantly short-er,the number of traversing platforms increased(P<0.05),and the exploratory trajectories were brief and clear.H&E staining re-sults showed that the cell layer of the Model group was thinned,the neurons were loosely arranged and disordered,the cell mem-branes of some cells were ruptured,the nuclei of the cells were deeply stained,the chromatin was cleaved,and the protrusions dis-appeared to varying degrees.Compared to the Model group,the above pathological changes were improved to different degrees in each medication group.The results of transmission electron microscope observation showed that the synaptic structure was incom-plete,the synaptic gap was blurred,the synaptic vesicles were reduced,and the presynaptic dense material was reduced in the Model group.The synaptic structure was relatively complete,the synaptic gap was clear,the synaptic vesicles were increased,the mitochondria were enriched,the presynaptic dense material was increased,and the postsynaptic membrane was thickened after the drug intervention.ELISA results showed that cAMP protein expression was significantly reduced in the Model group compared to the Control group(P<0.01);cAMP contents were significantly increased in the hippocampal region DPH and XST-H groups compared to the Model group(P<0.05),and cAMP contents in the cortical region of the DPH,XST-M,and XST-H groups were significantly elevated(P<0.05).Immunohistochemical results showed that the protein expression of SYN,GAP-43,and PSD-95 in the Model group showed a significant decreasing trend compared to the Control group(P<0.01).Compared to the Model group,the expression of the above proteins in the remaining groups increased to different degrees(P<0.05).Western blot results showed that PSD-95,GAP-4C3,CREB,PKA,and SYN protein expression was significantly reduced in the Model group compared to the Control group(P<0.05);and the expression levels of PSD-95,GAP-4C3,CREB,PKA,and SYN were in-creased to varying degrees after pharmacological interventions compared to the Model group(P<0.05).Conclusion:XST im-proves cognitive functions in Alzheimer's disease modeled mice,and its mechanism of action may be related to the activation of cAMP/PKA/CREB signaling pathway and repair of synaptic plasticity.关键词
血塞通软胶囊/阿尔茨海默病/突触可塑性/学习记忆能力Key words
Xuesaitong soft capsule/Alzheimer's disease/Synaptic plasticity/Learning and memory ability分类
医药卫生引用本文复制引用
胡小童,胡卓瑶,曹秀敏,安欣,黄雄峰,陈乔..血塞通软胶囊对东莨菪碱致阿尔茨海默病模型小鼠学习记忆能力及突触可塑性的影响研究[J].海南医科大学学报,2025,31(22):1718-1728,11.基金项目
江西省一流学科江西中医药大学中西医结合(zxyylxk20220103) （zxyylxk20220103）
江西省中医药管理局科技计划项目(2020B0331) （2020B0331）
江西省教育厅科学技术研究项目(GJJ211211)This study was supported by the Jiangxi Province First-class Discipline:Integrated Traditional Chinese and Western Medicine,Jiangxi University of Chinese Medicine(zxyylxk20220103) （GJJ211211）
Science and Technology Plan Project of Jiangxi Provincial Administration of Traditional Chinese Medicine(2020B0331) （2020B0331）
Science and Technology Research Project of Jiangxi Provincial Department of Education(GJJ211211) （GJJ211211）
