STAT3对阿尔茨海默病模型大鼠认知功能障碍的作用研究  

Study on the effect of STAT3 on cognitive impairment in Alzheimer's disease model rats

作　　者：余婷 刘海军 YU Ting;LIU Haijun(Neurology Department,Affiliated Hospital of Zunyi Medical University,Zunyi 563000;Graduate School,Zunyi Medical University,Zunyi 563006,China)

机构地区：[1]遵义医科大学附属医院神经内科,贵州遵义563000 [2]遵义医科大学研究生院,贵州遵义563006

出　　处：《临床医学研究与实践》2025年第7期1-4,12,共5页Clinical Research and Practice

基　　金：贵州省科技厅科技计划项目(黔科合支撑[2020]4Y144号);2018年贵州省卫生和计划生育委员会科学技术基金项目(No.gzwjkj2018-1-001);贵州省教育厅基础药理教育部重点实验室(遵义医学院)开放课题基金资助项目(黔教合KY字[2018]485);遵义医科大学“12345”未来人才培养计划“未来临床名医”项目(No.20211004);遵义医科大学研究生科研基金项目(No.ZYK153)。

摘　　要：目的探讨信号转导及转录活化因子-3(STAT3)对阿尔茨海默病(AD)模型大鼠认知功能的影响机制。方法在24只雄性SD大鼠的双侧海马区域给予5μL Aβ1-42寡聚体立体定位注射,以建立AD大鼠模型,随机将其分为正常组(CON组)、AD组、STAT3抑制剂组(Stattic组)、DMSO组,并进行Morris水迷宫(MWM)实验;采用Western blot法检测大鼠海马组织突触后致密蛋白95(PSD95)、STAT3蛋白表达情况。结果AD组的逃避潜伏期明显长于CON组(P<0.05);Stattic组的逃避潜伏期明显短于AD组(P<0.05)。AD组穿越平台的次数明显少于CON组(P<0.05);Stattic组穿越平台的次数多于AD组、DMSO组(P<0.05)。AD组的PSD95蛋白表达水平低于CON组,STAT3蛋白表达水平明显高于CON组(P<0.05)。Stattic组的PSD95蛋白表达水平高于AD组及DMSO组,STAT3蛋白表达水平低于AD组及DMSO组(P<0.05)。结论本研究初步验证了抑制STAT3的表达可改善突触可塑性,从而改善AD模型大鼠的认知功能。Objective To investigate the effect of signal transducer and activator of transcription-3(STAT3)on cognitive function in Alzheimer's disease(AD)model rats.Methods The AD rat model was established by stereotaxic injection of 5μL Aβ1-42 oligomers into the bilateral hippocampus of 24 male SD rats.The rats were randomly divided into normal group(CON group),AD group,STAT3 inhibitor group(Stattic group)and DMSO group,and Morris water maze(MWM)experiment was performed.The expression of postsynaptic density protein 95(PSD95)and STAT3 protein in hippocampus of rats were detected by Western blot.Results The escape latency of the AD group was significantly longer than that of the CON group(P<0.05);the escape latency of the Stattic group was significantly shorter than that of the AD group(P<0.05).The number of crossing the platform in the AD group was significantly less than that in the CON group(P<0.05);the number of crossing the platform in the Stattic group was more than that in the AD group and the DMSO group(P<0.05).The expression level of PSD95 protein in the AD group was lower than that in the CON group,and the expression level of STAT3 protein was significantly higher than that in the CON group(P<0.05).The expression level of PSD95 protein in the Stattic group was higher than that in the AD group and the DMSO group,and the expression level of STAT3 protein was lower than that in the AD group and the DMSO group(P<0.05).Conclusion This study preliminarily verified that inhibition of STAT3 expression can improve synaptic plasticity,thereby improving the cognitive function of AD model rats.

关 键 词：阿尔茨海默病 信号转导及转录活化因子-3 认知功能 突触可塑性 

分 类 号：R749.16[医药卫生—神经病学与精神病学]