摘要
目的基于小胶质细胞介导的神经炎症,探讨黄芪多糖对阿尔茨海默病(AD)小鼠的神经保护机制及对认知功能的影响。方法取10只野生型小鼠作为野生型组;另取20只5个家族性阿尔茨海默病基因突变(5×FAD)转基因小鼠,随机分为5×FAD转基因组和5×FAD转基因+黄芪多糖组,每组10只。5×FAD转基因+黄芪多糖组给予黄芪多糖200 mg/(kg·d)灌胃,野生型组和5×FAD转基因组小鼠给予等体积的生理盐水灌胃,均连续灌胃60 d。采用Morris水迷宫实验评估小鼠的空间学习与记忆能力,免疫组化染色观察海马区Iba1^(+)小胶质细胞的形态学特征,qRT-PCR法检测海马组织中白细胞介素-1β(IL-1β)、白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)mRNA表达情况,常规方法检测血常规(白细胞、红细胞、血小板计数)及肝肾功能指标(谷丙转氨酶、谷草转氨酶、肌酐)。结果与野生型组比较,5×FAD转基因组小鼠穿越平台次数明显减少(P<0.05),靶象限停留时间百分比明显降低(P<0.05);小胶质细胞呈明显活化状态,突起数量增加;海马组织中IL-1β、IL-6、TNF-αmRNA相对表达量均明显升高(P均<0.05)。与5×FAD转基因组比较,5×FAD转基因+黄芪多糖组小鼠穿越平台次数明显增加(P<0.05),靶象限停留时间百分比明显升高(P<0.05);活化的小胶质细胞数量减少;海马组织中IL-1β、IL-6、TNF-αmRNA相对表达量均明显降低(P均<0.05)。3组小鼠血常规、肝肾功能指标比较差异均无统计学意义(P均>0.05)。结论黄芪多糖可通过调节小胶质细胞活性和减轻神经炎症,改善5×FAD转基因小鼠认知功能。
Objective It is to explore the neuroprotective mechanism of Astragalus polysaccharides(APS)in Alzheimer’s disease(AD)mice and its effects on cognitive function based on microglia-mediated neuroinflammation.Methods Ten wild-type mice were taken as the wild-type group.Additionally,20 transgenic mice carrying 5 familial Alzheimer’s disease gene mutations(5×FAD)were taken and randomly divided into 5×FAD transgenic group and 5×FAD transgenic+APS group,with 10 mice in each group.The mice of the 5×FAD transgenic+APS group was given APS 200 mg/(kg·d)by gavage,the mice of the wild-type group and 5×FAD transgenic group were given equal volumes of normal saline by gavage,all groups were continuously treated for 60 days.The spatial learning and memory abilities of the mice were assessed by Morris water maze,the morphological changes in hippocampal Iba+microglia were observed by immunohistochemistry,and the mRNA expressions of interleukin-1β(IL-1β),interleukin-6(IL-6)and tumor necrosis factor-α(TNF-α)in hippocampal tissue were detected by qRT-PCR,the blood routine examination indicators(white blood cell,red blood cell and platelet counts)and liver and kidney function indicators(alanine aminotransferase,aspartate aminotransferase and creatinine)were measured by routine methods.Results Compared with the wild-type group,the platform crossing times and percentage of time spent in the target quadrant of mice in the 5×FAD transgenic were significantly decreased(all P<0.05),the microglia cells in the mice were obviously activated with increased neurite,the relative mRNA expressions of IL-1β,IL-6 and TNF-αin hippocampal tissue were significantly increased(all P<0.05).Compared with the 5×FAD transgenic group,the platform crossing times and percentage of time spent in the target quadrant of mice in the 5×FAD transgenic+APS group were significantly increased(all P<0.05),the quantity of activated microglia cells in the mice was obviously decreased,the relative mRNA expressions of IL-1β,IL-6 and TNF-αin hippocampal tissue were significantly decreased(all P<0.05).Conclusion Astragalus polysaccharides can improve cognitive function of 5×FAD transgenic mice via regulating microglial activity and alleviating neuroinflammation.
作者
崔晓丽
魏振
林姿
陈子博
李超
杜思哲
CUI Xiaoli;WEI Zhen;LIN Zi;CHEN Zibo;LI Chao;DU Sizhe(People’s Hospital Affiliated to Fujian University of Chinese Medicine,Fuzhou 350004,Fujian,China;Fujian Provincial Hospital Affiliated to Fuzhou University,Fuzhou 350001,Fujian,China)
出处
《现代中西医结合杂志》
2025年第15期2065-2069,2088,共6页
Modern Journal of Integrated Traditional Chinese and Western Medicine
基金
福建省自然科学基金项目(2022J01849)
福建省中青年教师教育科研项目(JAT210165)。
关键词
阿尔茨海默病
黄芪多糖
小胶质细胞
认知功能
神经炎症
Alzheimer’s disease
Astragalus polysaccharides
microglia
cognitive function
neuroinflammation
