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
王姝涵,第一作者,研究方向:神经退行性疾病机制研究,E-mail:1164856840@qq.com
纸质出版日期:2023-11-20,
收稿日期:2023-03-06,
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王姝涵,杨翠珠,张润恒等.紫云英苷抑制APP/PS1小鼠大脑皮质神经元凋亡[J].中山大学学报(医学科学版),2023,44(06):983-990.
WANG Shu-han,YANG Cui-zhu,ZHANG Run-heng,et al.Astragalin Inhibits Apoptosis of Cerebral Cortex Neurons in APP/PS1 Mice[J].Journal of Sun Yat-sen University(Medical Sciences),2023,44(06):983-990.
王姝涵,杨翠珠,张润恒等.紫云英苷抑制APP/PS1小鼠大脑皮质神经元凋亡[J].中山大学学报(医学科学版),2023,44(06):983-990. DOI: 10.13471/j.cnki.j.sun.yat-sen.univ(med.sci).2023.0612.
WANG Shu-han,YANG Cui-zhu,ZHANG Run-heng,et al.Astragalin Inhibits Apoptosis of Cerebral Cortex Neurons in APP/PS1 Mice[J].Journal of Sun Yat-sen University(Medical Sciences),2023,44(06):983-990. DOI: 10.13471/j.cnki.j.sun.yat-sen.univ(med.sci).2023.0612.
目的
2
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
2
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
2
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-Caspase3
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
<
0.000 1,
P
<
0.000 1),上调
Bcl-2
(
P
<
0.05,
P
<
0.05)。
结论
2
AST能够抑制APP/PS1小鼠大脑皮质神经元凋亡。
Objective
2
To investigate the effect of Astragalin (AST) on apoptosis of cerebral cortex neurons in APP/PS1 transgenic mice.
Methods
2
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 proteins
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
2
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
,
Caspase9
, and
Cleaved-Caspase3
,
and icreased the expression of
Bcl-2
in the cerebral cortex neurons of APP/PS1 mice. Western blot results further confirmed that 40 mg/kg AST and 20 mg/kg DNP both down-regulated the expression of
Bax
(
P
<
0.05,
P
<
0.05),
Caspase9
(
P
<
0.005,
P
<
0.05) and
Caspase3
(
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/PS1 mice.
Conclusions
2
AST can inhibit the apoptosis of cerebral cortex neurons in APP/PS1 mice.
紫云英苷APP/PS1小鼠大脑皮质神经元凋亡
astragalin (AST)APP/PS1 micecerebral cortexneuronapoptosis
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