紫云英苷抑制APP/PS 1小鼠大脑皮质神经元凋亡  

Astragalin Inhibits Apoptosis of Cerebral Cortex Neurons in APP/PS 1 Mice

作　　者：王姝涵 杨翠珠 张润恒 林佳泓 杨雅琪 刘靖[1] 李国营[1] 马宇昕[1] WANG Shu-han;YANG Cui-zhu;ZHANG Run-heng;LIN Jia-hong;YANG Ya-qi;LIU Jing;LI Guo-ying;MA Yu-xin(Department of Human Anatomy,Histology and Embryology,School of Life Sciences and Biopharmaceutics,Guangdong Pharmaceutical University,Guangzhou 510006,China)

机构地区：[1]广东药科大学基础医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）》2023年第6期983-990,共8页Journal of Sun Yat-Sen University:Medical Sciences

基　　金：广东省医学科学技术研究基金(B2022076);广东省中医药局中医药科研项目(20231201、20221213);广州市基础与应用基础研究项目(202201010181);广东省普通高校特色创新类项目(2023KTSCX057)。

摘　　要：【目的】探讨紫云英苷(AST)对APP/PS1转基因小鼠大脑皮质神经元凋亡的影响。【方法】将18只6月龄雄性APP/PS1转基因小鼠随机分为APP/PS1、APP/PS1+40 mg/kg AST、APP/PS1+20 mg/kg DNP(Donepezil,DNP)三组,每组各6只动物。同时另选6只同月龄C57BL/6雄性小鼠作为正常对照组(Control)。腹腔注射给药AST,每日一次,连续给药一个月后,Tunel染色法检测APP/PS1小鼠大脑皮质内神经元凋亡情况;免疫荧光染色法检测APP/PS1小鼠大脑皮质内神经元凋亡相关蛋白Bax、Bcl-2、Caspase9、Cleaved-Caspase3表达情况;Western blot法检测APP/PS1小鼠大脑皮质内Bax、Bcl-2、Caspase9及Caspase3表达水平的变化。【结果】Tunel染色结果显示,40 mg/kg AST及20 mg/kg DNP均可减少APP/PS1小鼠大脑皮质内神经元凋亡,其中AST抑制效果尤为明显。免疫荧光染色结果表明,40 mg/kg AST及20 mg/kg DNP均抑制APP/PS1小鼠大脑皮质内神经元中Bax、Caspase9及Cleaved-Cas⁃pase3的表达,增加Bcl-2的表达。Western blot结果进一步证实,40 mg/kg AST及20 mg/kg DNP均可下调APP/PS1小鼠大脑皮质内神经元Bax(P<0.05,P<0.05)、Caspase9(P<0.005,P<0.05)及Caspase3(P<0.0001,P<0.0001),上调Bcl-2(P<0.05,P<0.05)。【结论】AST能够抑制APP/PS1小鼠大脑皮质神经元凋亡。【Objective】To investigate the effect of Astragalin(AST)on apoptosis of cerebral cortex neurons in APP/PS1 transgenic mice.【Methods】Eighteen six-month-old male APP/PS1 transgenic mice were randomly divided into APP/PS1 group,APP/PS1+40 mg/kg AST group and APP/PS1+20 mg/kg Donepezil(DNP)group,with six mice in each group.At the same time,six male C57BL/6 mice were selected as the normal control group.After intraperitoneal injection of AST once a day and continuous administration for one month,we used Tunel staining to detect the apoptosis of neurons in the cerebral cortex of APP/PS1 mice;immunofluorescent staining to examine the expression of apoptosis-related pro⁃teins Bax,Bcl-2,Caspase9 and Cleaved-Caspase3 in the cerebral cortex neurons of APP/PS1 mice;Western blot method to evaluate the changes of the expression of Bax,Bcl-2,Caspase9 and Caspase3.【Results】Tunel staining showed that 40 mg/kg AST and 20 mg/kg DNP both reduced the apoptosis of neurons in the cerebral cortex of APP/PS1 mice,AST with more significant inhibition effect.Immunofluorescent staining revealed that 40 mg/kg AST and 20 mg/kg DNP both inhibited the expression of Bax,Caspase 9,and Cleaved-Caspase 3,and icreased the expression of Bcl-2 in the cerebral cortex neurons of APP/PS 1 mice.Western blot results further confirmed that 40 mg/kg AST and 20 mg/kg DNP both down-regulat⁃ed the expression of Bax(P<0.05,P<0.05),Caspase 9(P<0.005,P<0.05)and Caspase 3(P<0.0001,P<0.0001),and up-regulated the expresstion of Bcl-2(P<0.05,P<0.05)in the cerebral cortex neurons of APP/PS 1 mice.【Conclusions】AST can inhibit the apoptosis of cerebral cortex neurons in APP/PS 1 mice.

关 键 词：紫云英苷 APP/PS1小鼠 大脑皮质 神经元 凋亡 

分 类 号：R285.5[医药卫生—中药学]