丁酸钠改善阿尔茨海默病模型的病理作用机制探讨  

Investigation of the mechanisms of action of sodium butyrate in ameliorating the pathological processes in an Alzheimer's disease model

作　　者：许嘉熙 廖峥娈[2] 于恩彦 Xu Jiaxi;Liao Zhengming;Yu Enyan(Department of Mental Health,Zhejiang Tongde Hospital,Hangzhou 311122,China;Department of Clinical Psychology,Zhejiang People's Hospital,Hangzhou 314408,China;Department of Clinical Psychology,Affiliated Cancer Hospital,University of the Chinese Academy of Sciences,Hangzhou 310012,China)

机构地区：[1]浙江省立同德医院精神卫生科,杭州311122 [2]浙江省人民医院临床心理科,杭州314408 [3]中国科学院大学附属肿瘤医院临床心理科,杭州310012

出　　处：《中华老年医学杂志》2023年第11期1337-1342,共6页Chinese Journal of Geriatrics

基　　金：浙江省重点研发计划项目(2021C03106)。

摘　　要：目的探究丁酸钠(NaB)对阿尔茨海默病(AD)病理模型的自噬和炎症的影响及其作用机制。方法使用Aβ25-35作用于PC12细胞建立体外AD模型, 通过NaB对体外AD模型和小胶质细胞BV2进行处理, 分组设置分别为:PC12细胞、PC12细胞+Aβ25-35、PC12细胞+Aβ25-35+NaB;BV2细胞、BV2细胞+Aβ25-35、BV2细胞+Aβ25-35+NaB。使用蛋白质印迹法、免疫荧光、EdU染色法评估自噬通路及炎性蛋白标记物的表达。结果 NaB可以促进AD模型细胞的增殖, 降低Tau蛋白过度磷酸化水平。NaB可以抑制小胶质细胞的炎症反应, 降低炎症反应标志物核苷酸结合寡聚化结构域样受体蛋白3(NLRP3)(148.313±0.973和113.291±1.218, t=38.91, P<0.001)的表达。同时, NaB促进小胶质细胞中自噬通路蛋白(包括Beclin-1、LAMP-1和LC3Ⅱ/Ⅰ)的表达。结论 NaB可以通过促进自噬和减少炎症反应来改善AD模型的病理。Objective To investigate the effects of sodium butyrate(NaB)on pathological processes such as autophagy and inflammation in an Alzheimer's disease(AD)model and related mechanisms.Methods Aβ25-35's action on PC12 cells was used to establish an in vitro AD model,in which microglial BV2 were treated with NaB.Based on treatments,there were a PC12 cells group,a PC12 cells+Aβ25-35 group,a PC12 cells+Aβ25-35+NaB group,a BV2 cells group,a BV2 cells+Aβ25-35 group,and a BV2 cells+Aβ25-35+NaB group.The expression of markers of the autophagy pathway and inflammatory proteins was evaluated by Western blot,immunofluorescence and EdU staining.Results NaB was able to promote cell proliferation in the AD model and reduce the level of Tau protein hyperphosphorylation.NaB also inhibited the inflammatory response of microglia and reduce the expression of inflammatory response marker NLRP3(148.313±0.973 us.113.291±1.218,t=38.91,P<0.001).At the same time,NaB promoted the expression of autophagy pathway proteins(including Beclin-1,LAMP-1 and LC3 II/I)in microglia.Conclusions NaB can mitigate pathological changes in an AD model by promoting autophagy and reducing the inflammatory response.

关 键 词：阿尔茨海默病 炎症 自噬 丁酸钠 

分 类 号：R749.16[医药卫生—神经病学与精神病学] R-332[医药卫生—临床医学]