摘要
目的探讨丙戊酸钠(valproic acid sodium salt,VPA)处理对淀粉样蛋白前体蛋白(β-amyloid pre-cursor protein,APP)/早老素1(presenilin1,PS1)双重转基因阿尔茨海默病(Alzheimer's disease,AD)模型小鼠是否发挥神经保护作用。方法对APP/PS1双重转基因AD模型种鼠交配后产下的子代进行基因分型,运用VPA30mg/(kg·d)和等量生理盐水腹腔注射APP/PS1双重转基因小鼠4周。药物处理后采用免疫组化、甲硫素S染色检测VPA对老年斑(senile plapues,SP)的影响,用Nissl染色、Tunel染色观察脑内神经元的变化,并采用ELISA定量检测小鼠脑内β-淀粉样蛋白(amyloidβpeptide,Aβ)水平。结果免疫组化及甲硫素S染色结果显示:VPA治疗组较生理盐水组的小鼠大脑皮质及海马区域的老年斑数量明显减少(t=7.78,P<0.01)。Nissl染色发现VPA治疗组小鼠皮质及海马内的神经元数目较生理盐水组增加;Tunel染色显示VPA治疗组小鼠脑内凋亡神经元明显减少(t=5.95,P<0.01);ELISA结果提示VPA治疗组小鼠脑内Aβ40(t=4.23,P<0.01)和Aβ42(t=7.51,P<0.01)水平显著低于对照组。结论 VPA处理能显著减少AD模型小鼠减少脑内Aβ的沉积和老年斑的形成,通过减少神经元的凋亡来增加神经元的数量。
Objective To investigate whether valproie acicl （VPA）exert neuroprotective effect on β-amyloid precursor protein （APP）/presenilinl （PS1） double transgenic Alzheimer＇s disease （AD） mouse model. Methods Offspring of APP/PS1 double transgenic AD mice were genotyped. VPA at 30 mg/（kg.d） and the same amount of saline were peritoneally injected into APP/PS1 double transgenic mice for 4 weeks. Immunohistoehemical, Thioflavin S Nissl and TUNEL staining as well as ELISA assay were performed in the present study. Results Immuohistochemical and Thioflavin S stainings showed that the number and size of senile plaques （SP） in the cerebral cortex and hippoeampus of VPA-treated mice were notably decreased （t = 7.78,P 〈 0.01）; The number of neurons were increased, while the number of apoptotic neurons were reduced in the brain of VPA-treated mice （t = 5.95, P 〈 0.01 ）, as revealed by Nissl and TUNEL stainings. ELISA assay showed that Aβ40 （t = 4.23, P 〈 0.01） and Aβ42 （t = 7.51, P 〈 0.01） level were sig- nificantly decreased in the brain of VPA-treated mice compared with the control. Conclusion VPA can significantly reduce Abeta deposition and formation of SP and increase the number of neurons probably through reducing the apoptotic neuron in the brain of APP/PS1 transgenic mouse.
出处
《中国神经精神疾病杂志》
CAS
CSCD
北大核心
2011年第8期477-481,共5页
Chinese Journal of Nervous and Mental Diseases
基金
国家自然科学基金(编号:30970986)
