丹皮酚对APP/PS1阿尔茨海默病小鼠的治疗作用

Therapeutic effect of paeonol on APP/SP1 Alzheimer′s disease mice

目的研究丹皮酚(paeonol,Pae)对APP/PS1小鼠学习记忆能力、淀粉样斑块沉积、脑内神经元异常活动和神经元凋亡的改善作用。方法采用饮食中补充Pae(50 mg·kg-1·d-1)的饲养方案喂养APP/PS1小鼠3个月,通过水迷宫实验研究小鼠的学习记忆能力;通过脑电图记录研究小鼠神经元放电活动;通过硫代黄素-S染色和Aβ免疫荧光观察小鼠海马及皮质中淀粉样斑块沉积;分别通过原位末端转移酶标记技术(terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay,TUNEL)染色和Western blot实验检测小鼠海马神经元凋亡以及凋亡相关蛋白的表达水平。结果Pae可以显著改善APP/PS1小鼠的学习记忆能力,减少海马及皮质中淀粉样斑块沉积,并有效降低了脑内的神经元异常放电活动。并且Pae可以减少APP/PS1小鼠海马神经元凋亡并降低海马中Cleaved caspase-3/caspase-3和Bax/Bcl-2比值。结论Pae可改善APP/PS1小鼠记忆功能受损,并减少海马和皮质中淀粉样斑块沉积并降低神经元凋亡水平。

Objective To study the improvement effect of paeonol(Pae)on the ability of learning and memory,amyloid plaque deposition,abnormal neuronal activity and neuronal apoptosis in the brain of APP/PS1 mice.Methods APP/PS1 mice were fed with a supplement Pae(50 mg·kg-1·d-1)in diet feeding regimen for 3 months.The learning and memory ability in mice was studied by water maze test.The firing activity of neurons in mice was recorded by electroencephalogram.The amyloid plaque deposition in hippocampus and cortex of mice was observed by thioflavine-S staining and Aβimmunofluorescence.Neuronal apoptosis and the expression levels of apoptosis-related proteins in the hippocampus of mice were detected by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay(TUNEL)staining and Western blot,respectively.Results Pae significantly improved the learning and memory ability of APP/PS1 mice,reduced the deposition of amyloid plaques in the hippocampus and cortex,and effectively decreased the abnormal firing activity of neurons in the brain.In addition,Pae reduced the apoptosis of hippocampal neurons in APP/PS1 mice and decreased the ratios of Cleaved caspase-3/caspase-3 and Bax/Bcl-2 in the hippocampus.Conclusion Pae improves memory impairment in APP/PS1 mice,reduces amyloid plaque deposition and neuronal apoptosis in hippocampus and cortex.