药学研究2025，Vol.44Issue(6)：528-535,8.DOI:10.13506/j.cnki.jpr.2025.06.002
马赛替尼减轻丙烯醛诱导的sAD模型小鼠神经病理学改变的作用研究
Masitinib attenuates neuropathological changes in acrolein-induced sAD model mice
摘要
Abstract
Objective To explore the therapeutic effects of Masitinib in acrolein-induced sporadic Alzheimer's disease(sAD)model mice and explore its underlying mechanisms.Methods Male C57BL/6 mice were administered acrolein[3 mg·(kg·d)-1]by gavage for 10 weeks,with Masitinib[60 mg·(kg·d)-1]co-administered from the 5th week for 6 weeks.Behavioral tests,including the buried food pellet test,Morris water maze,Y-maze,open field test,and elevated plus maze,were conducted at the 9th week.Cortical and hippocampal tissues were then collected for pathological assessments using Western blotting,immunofluorescence staining,and Golgi-Cox staining.Results Masitinib significantly ameliorated acrolein-induced olfactory deficits,cognitive dysfunction,and anxiety-like behaviors.Furthermore,Masitinib not only reduced phosphorylated Tau(p-Tau)levels,increased postsynaptic density protein 95(PSD95)expression,and restored dendritic spine density but also exerted anti-neuroinflammatory effects by suppressing the NF-κB/NLRP3/caspase-1 sig-naling pathway and microglial activation.Conclusion This study is the first to demonstrate that Masitinib mitigates sAD progression through dual mechanisms involving cognitive improvement and neuroprotection,providing crucial experimental evidence for its clinical translation.关键词
马赛替尼/散发性阿尔茨海默病/丙烯醛/认知功能障碍/神经炎症Key words
Masitinib/Sporadic Alzheimer's disease/Acrolein/Cognitive dysfunction/Neuroinflammation分类
医药卫生引用本文复制引用
贾康,沈千惠,张志先,刘源,皮荣标,周四桂..马赛替尼减轻丙烯醛诱导的sAD模型小鼠神经病理学改变的作用研究[J].药学研究,2025,44(6):528-535,8.基金项目
国家自然科学基金项目(No.81671264) （No.81671264）
深圳市港澳科技计划A类项目(No.202111233000079) （No.202111233000079）
广州市科技计划项目(No.SL2023B03J00817) （No.SL2023B03J00817）
