紫云英苷诱导自噬减轻APP/PS1转基因小鼠皮质内神经元损伤及老年斑沉积  

Astragalin Alleviates Neuronal Damage and Senile Plaque Deposition via Activating Autophagy in the Cortex of APP/PS1 Transgenic Mice

作　　者：杨翠珠 张润恒 王姝涵 蒋裕芸 刘靖 李国营 马宇昕 YANG Cui-zhu;ZHANG Run-heng;WANG Shu-han;JIANG Yu-yun;LIU Jing;LI Guo-ying;MA Yu-xin(Department of Human Anatomy and Histology and Embryology,School of Life Sciences and Biopharmaceutics,Guangdong Pharmaceutical University,Guangzhou 510006,China)

机构地区：[1]广东药科大学生命科学与生物制药学院人体解剖与组织胚胎学系,广东广州510006

出　　处：《中山大学学报（医学科学版）》2022年第2期238-246,共9页Journal of Sun Yat-Sen University:Medical Sciences

基　　金：广东省自然科学基金(2018A0303130073);广东省医学科学基金(2018464);广州市科技计划项目科技创新人才专项-珠江科技新星(201710010002)。

摘　　要：【目的】探讨紫云英苷(AST)对APP/PS1转基因小鼠脑皮质神经元及Aβ斑块的影响。【方法】将24只8月龄雄性APP/PS1转基因小鼠随机分为APP/PS1组、10 mg/kg AST(APP/PS1+AST 10)组、20 mg/kg AST(APP/PS1+AST 20)组、40 mg/kg AST(APP/PS1+AST 40)组,每组各6只。6只同月龄C57BL/6雄性小鼠作为对照组(WT组)。AST药物连续腹腔注射一个月后,采用免疫荧光染色法观察小鼠脑皮质内Aβ斑块沉积情况,尼氏染色法观察皮质内神经元数量及形态变化,免疫荧光多重染色法观察小鼠脑皮质内LC3B、p62分别与NeuN共表达情况。Western blot法检测皮质中NeuN、LC3B及p62蛋白表达情况。【结果】免疫荧光染色法表明,20、40 mg/kg AST均可减少APP/PS1转基因小鼠脑皮质内Aβ斑块沉积(P<0.0001;P<0.0001)。Western blot结果表明,20、40 mg/kg AST均可增加APP/PS1转基因小鼠脑皮质内NeuN蛋白表达量(P=0.0121;P<0.0001)。免疫荧光多重染色结果揭示APP/PS1转基因小鼠脑皮质内LC3B、p62与NeuN均存在共表达现象。Western blot结果表明,AST增加APP/PS1转基因小鼠脑皮质内LC3B表达量(P=0.007,P<0.0001),减少p62表达量(P<0.0001,P<0.0001)。【结论】AST通过激活自噬减轻APP/PS1转基因小鼠脑皮质内神经元损伤及Aβ斑块沉积。【Objective】To explore the effect of astragalin(AST)on neurons and Aβplaques in the cortex of APP/PS1 transgenic mice.【Methods】Twenty-four 8-month-old male APP/PS1 transgenic mice were randomly divided into APP/PS1 group,10 mg/kg AST(APP/PS1+AST 10)group,and 20 mg/kg AST(APP/PS1+AST 20)group,40 mg/kg AST(APP/PS1+AST 40)group,with 6 mice in each group.Six C57BL/6 male mice of the same age served as the control group(WT group).AST drugs were continuously injected intraperitoneally for one month.Then Immunofluorescent staining was used to observe the deposition of Aβplaques in the cortex.Nissl staining was used to observe the number and morphologi⁃cal changes of neurons in the cortex,and immunofluorescent multiple staining methods were used to observe the co-expres⁃sion of LC3B,p62 and NeuN in the cortex.Then the expressions of NeuN,LC3B,and p62 protein were detected by West⁃ern blot method.【Results】Immunofluorescent staining results showed 20 mg/kg and 40 mg/kg AST reduced Aβplaques de⁃position in the cortex of APP/PS1 mice(P<0.0001;P<0.0001).Western blot analysis showed both 20 and 40 mg/kg AST increased the expression of NeuN protein in the cortex of APP/PS1 mice(P=0.0121;P<0.0001).Immunofluores⁃cent multiplex staining showed co-expression of LC3B,p62,and NeuN in the cortex of APP/PS1 mice.Western blot analy⁃sis showed AST increased the expression of LC3B(P=0.007,P<0.0001)and decreased the expression of p62(P<0.0001,P<0.0001)in the cortex of APP/PS1 mice.【Conclusions】AST reduces neuronal damage and Aβplaques depo⁃sition in the cortex of APP/PS1 mice by activating autophagy.

关 键 词：紫云英苷 APP/PS1转基因小鼠 自噬 神经元损伤 Aβ斑块沉积 

分 类 号：R285.5[医药卫生—中药学]