STAT3在阿尔茨海默病小鼠认知障碍发生发展中的作用及机制研究  

STAT3 inhibitor niclosamide improves the cognitive impairment in mice with Alzheimer's disease and related mechanism

作　　者：王珏[1] 陈佩弦 何玲[1] 孙逸 WANG Jue;CHEN Pei-xian;HE Ling;SUN Yi(School of Pharmacy,China Pharmaceutical University,Nanjing 211198)

机构地区：[1]中国药科大学药学院,南京211198

出　　处：《中南药学》2024年第1期17-23,共7页Central South Pharmacy

基　　金：国家自然科学基金青年项目(No.81703520);宁夏回族自治区重点研发计划重点项目(No.2019BFG02017);江苏省高等学校大学生创新创业训练计划项目成果(No.202310316044Y)。

摘　　要：目的 研究信号传导及转录激活因子3(STAT3)在阿尔茨海默病小鼠认知障碍发生发展中的作用及机制。方法 利用C57BL/6J小鼠双侧海马脑立体定位注射β-淀粉样蛋白建立阿尔茨海默病模型,给予STAT3抑制剂氯硝柳胺,运用动物行为学分析检测、Western blot分析检测等探究STAT3在认知障碍中的作用及机制。结果 行为学实验表明,与模型组小鼠相比,给药组小鼠的焦虑症状、空间探索能力、物体识别能力和学习记忆能力均得到改善;Western blot分析结果表明,给药后小鼠阿尔茨海默病的病理标志物改善,促炎因子表达下调;试剂盒分析结果显示给药组小鼠氧化应激相关指标改善;HE染色结果显示给药组小鼠海马神经元组织形态的改善。结论 本研究初步证明了抑制STAT3可减轻神经炎症和氧化应激,从而改善阿尔茨海默病小鼠的认知障碍。Objective To determine the effect and mechanism of signal transducers and activators of transcription 3(STAT3) in the occurrence and development of cognitive impairment in mice with Alzheimer's disease.Methods Alzheimer's disease model was established by stereotaxic injection of β-amyloid protein into the bilateral hippocampus of C57BL/6J mice.Then niclosamide,an inhibitor of STAT3 was given.Animal behavior analysis and Western blot were used to determine the effect and mechanism of STAT3 in the cognitive impairment.Results The behavior test showed that compared with the model group,the anxiety symptoms,spatial exploration ability,object recognition ability and learning and memory were improved ability in the treatment group.Western blot showed that the pathological markers of Alzheimer's disease were improved and the expression of pro-inflammatory factors was down-regulated.The oxidative stress related indexes of the treatment group were improved by kit analysis.HE staining showed that the histomorphology of the hippocampal neurons in the treatment group was improved.Conclusion It is preliminarily proved that inhibition of STAT3can reduce the neuroinflammation and oxidative stress and improve the cognitive impairment in mice with Alzheimer's disease.

关 键 词：阿尔茨海默病 神经炎症 信号传导及转录激活因子3 氯硝柳胺 

分 类 号：R749.16[医药卫生—神经病学与精神病学]