齐墩果酸对APP/PS-1双转基因AD小鼠的神经保护作用研究  

The Effect of Oleanolic Acid on APP/PS-1 Double Transgenic AD Mice

作　　者：再娜甫古丽·买买提 马心念 古力夏提·艾力 张鹏 袁芳[1] MAIMAITI·Zai-na-fu-li;MA Xin-nian;AILI·Gu-i-xia-tr;ZHANG Peng;YUAN Fang(School of Basic Medical Science,Xinjiang Key Laboratory of molecular Biology for Endemic Disease;School of Public Health,Xinjiang Medical University,Urumqi,Xinjiang,830000,China)

机构地区：[1]新疆医科大学基础医学院新疆地方病分子生物学重点实验室,新疆乌鲁木齐830000 [2]新疆医科大学公共卫生学院,新疆乌鲁木齐830000

出　　处：《现代生物医学进展》2023年第24期4614-4619,共6页Progress in Modern Biomedicine

基　　金：国家自然科学基金项目(81960764)。

摘　　要：目的:研究齐墩果酸(Oleanolic Acid,OA)对APP/PS-1双转基因阿尔茨海默病(Alzheimer's disease,AD)小鼠模型神经保护作用及机制。方法:选取6月龄APP/PS-1雄性小鼠21只,随机分为模型组(0.5%CMC-Na)、阳性组(多奈哌齐组,0.7 mg·kg^(-1))、齐墩果酸组(10 mg·kg^(-1))每组7只,6月龄同背景SPF级C57BL/6小鼠7只为对照组。灌胃8周之后通过Morris水迷宫实验观察小鼠学习记忆能力的改变,HE染色观察神经元细胞形态,ELISA检测血清中Aβ_(1-42)含量;免疫组化检测Aβ_(1-42)、APP、Iba1蛋白表达情况;Western blot检测APP、Iba1蛋白表达水平。结果:(1)对照组,模型组,阳性组及齐墩果酸组进入有效区域次数分别为7.00±2.09,1.00±0.89,3.67±1.97,4.33±2.50,与模型组相比,对照组,阳性组,齐墩果酸组均有统计学意义(P<0.05);(2)血清Aβ_(1-42)含量按上述顺序依次为4.98±0.25,2.50±0.66,4.63±0.73,4.36±0.97,与模型组相比,对照组,阳性组,齐墩果酸组均有统计学意义(P<0.05);(3)免疫组化结果显示与模型组相比,对照组,阳性组,齐墩果酸组Aβ_(1-42)、APP、Iba1蛋白阳性细胞数减少;(4)WB结果:对照组,模型组,阳性组,齐墩果酸组APP蛋白相对表达量分别为0.52±0.17,1.38±0.35,0.89±0.25,0.93±0.27;这四组的IBA1蛋白相对表达量分别为0.98±0.34,1.79±0.74,1.06±0.61,0.88±0.49,与模型组相比,野生对照组,阳性组,齐墩果酸组APP、IBA1蛋白相对含量有统计学意义(P<0.05)。结论:齐墩果酸组可以改善APP/PS-1模型小鼠记忆力及认知功能,降低海马神经元的损伤,并通过下调Aβ_(1-42)、APP、Iba1蛋白的表达水平来发挥保护神经作用。Objective:To investigate the brain protection mechanism of oleanolic acid on APP/PS-1 double transgenic mice with Alzheimer's disease(AD).Methods:216-month-old AD mice were casually divided into model group(0.5%CMC-Na),positive admin-istration group(donepezil group,0.7 mg·kg^(-1))and oleanolic acid group(10 mg·kg^(-1)),while C57BL/6 mice were chosen as control group.8 weeks later,we use water maze to observe the spatial cognitive ability of mice.He staining was used to observe the morphology of neu-rons,and ELISA was used to detect the content of Aβ_(1-42) in serum.The protein expression levels of Aβ_(1-42),APP and Ibal were detected by immunohistochemistry.Western blot used to detect APP and Ibal protein expression levels.Results:(1)The Times of entering effec-tive area in control group,model group,positive group and oleanolic acid group were 7.00±2.09,1.00±0.89,3.67±1.97,4.33±2.50.Compared with model group,control group,positive group and oleanolic acid group was significantly increased(P<0.05).(2)The con-tents of Aβ_(1-42) in serum were 4.98±0.25,2.50±0.66,4.63±0.73 and 4.36±0.97,compared with model group,wild control group,posi-tive group and oleanolic acid group was significantly reduced(P<0.05);(3)Compared with model group,the number of Aβ_(1-42),APP and Ibal protein positive cells in control group,positive group and oleanolic acid group decreased;(4)WB results The relative expression of APP protein in wild control group,model group,positive group and oleanolic acid group were 0.52±0.17,1.38±0.35,0.89±0.25 and 0.93±0.27.The relative expression levels of IBA1 protein in the four groups were 0.98±0.34,1.79±0.74,1.06±0.61 and 0.88±0.49.Compared with the model group,the relative content of APP and IBA1 protein in the wild control group,positive group and oleanolic acid group was significantly decreased(P<0.05).Conclusion:Oleanolic acid group can protect the memory and cognitive function of APP/PS-1 model mice,reduce the damage of hippocampal neurons,and play a neuroprotective role by down-

关 键 词：阿尔茨海默病 APP/PS-1双转基因AD小鼠 齐墩果酸 Β淀粉样蛋白 

分 类 号：R-33[医药卫生] R749.16