大豆肽改善阿尔茨海默病小鼠学习记忆行为的抗氧化应激和抗凋亡机制  

Soybean peptide ameliorating the cognitive function of mice with Alzheimer's disease induced by Aβ25~35 via anti-oxidative stress and apoptosis

作　　者：刘卫云[1] 程志国 徐宛玲[3] 崔明辰[3] 徐松涛[3] 李盘欣 金少举[3] 马永超[3,4] LIU Wei-Yun;CHENG Zhi-Guo;XU Wan-Ling(Chengde Nursing Vocational College,Chengde 067000,Hebei,China)

机构地区：[1]承德护理职业学院,河北承德067000 [2]河北省滦平县小营乡卫生院 [3]漯河医学高等专科学校生物化学教研室河南省肿瘤发生与防治创新型科技团队 [4]河南省南街村(集团)有限公司

出　　处：《中国老年学杂志》2020年第8期1727-1732,共6页Chinese Journal of Gerontology

基　　金：河南省科技攻关计划项目(152102210209,152102310219);河南省博士后基金项目(2014102)。

摘　　要：目的探讨大豆肽改善阿尔茨海默病(AD)小鼠学习记忆行为的抗氧化应激和抗凋亡机制。方法将60只经水迷宫实验筛选合格的小鼠随机分为阴性对照组(生理盐水)、模型组(生理盐水)、阳性药对照组(多奈哌齐5 mg/kg)及大豆肽600、300及150 mg/kg剂量组各10只。采用侧脑室注射Aβ25~35法建立AD小鼠模型。Morris水迷宫试验测试小鼠学习、记忆能力;生化法测定脑组织超氧化物歧化酶(SOD)、丙二醛(MDA)、谷胱甘肽过氧化物酶(GSH-Px)及总抗氧化能力(T-AOC)水平;Tunel法测定海马神经元凋亡情况;RT-PCR和Western印迹法检测海马组织细胞色素(Cyt)C、Caspase-3、B细胞淋巴瘤(Bcl-2)及Bcl-2相关X蛋白(Bax)mRNA和蛋白表达水平。结果与阴性对照组比较,模型组定位航行逃避潜伏期明显延长、穿越原跳台位置次数和在原跳台所在象限停留时间明显减少(P<0.01);脑组织SOD、GSH-Px及T-AOC水平显著降低,MDA含量显著增多(P<0.01);Tunel染色试验可见海马区有多量散在染色凋亡神经元;海马组织CytC、Caspase-3及Bax mRNA和蛋白表达水平显著上调,Bcl-2 mRNA和蛋白表达水平显著下调(P<0.01)。与模型组比较,大豆肽600 mg/kg组定位航行逃避潜伏期显著缩短、穿越原跳台位置次数和在原跳台所在象限停留时间显著增多(P<0.05,P<0.01);脑组织SOD、GSH-Px及T-AOC水平明显升高,MDA含量显著降低(P<0.05,P<0.01);Tunel染色试验可见海马区有少量散在染色凋亡神经元;海马组织Cyt C、Caspase-3及Bax mRNA和蛋白表达水平显著下调,Bcl-2 mRNA和蛋白表达水平显著上调(P<0.01)。结论大豆肽防治AD与其抗氧化应激及抗细胞凋亡有关。Objective To observe the effect of soybean peptide(SP)on cognitive function of mice with Alzheimer's disease(AD),and to explore its anti-oxidative stress and anti-apoptotic mechanism.Methods Sixty mice were randomly divided into negative control,model,positive control(Donepezil,5 mg/kg),and soybean peptide 600,300 and 150 mg/kg groups.The AD mice were induced by intracerebroventricular injections of Aβ25~35.Morris water maze was used to test the learning and memory capability of mice.The levels of SOD,MDA,GSH-Px and T-AOC in brain tissue of mice were detected by biochemical method.The apoptosis of hippocampal neurons of mice were observed by TUNEL method.The expression levels of Cyt C,Caspase-3,Bax and Bcl-2 in hippocampal tissue of mice were detected by RT-PCR and Western blot method.Results Compared with the negative control group,the escape latency of AD model mice was prolonged,the times of crossing the original platform and the stay time in the former platform quadrant were decreased;the levels of SOD,GSH-Px and T-AOC in brain tissue of AD mice were decreased significantly,while the content of MDA was increased;the Tunel staining test showed that there were a larger number of apoptotic neurons were scattered in the hippocampus of AD mice;the expression levels of Cyt C,Caspase-3 and Bax mRNA and protein in hippocampus tissue of AD mice were up-regulated,while the Bcl-2 was down-regulated.Compared with the AD model group,the SP 600 mg/kg could shorten the escape latency of AD mice,increase the times of crossing the original platform and the stay time in the former platform quadrant;could increase the levels of SOD,GSH-Px and T-AOC in brain tissue of AD mice,decrease the content of MDA;could reduce the hippocampus neuron apoptotic of AD mice;could down-regulate the expression levels of Cyt C,Caspase-3 and Bax mRNA and protein in hippocampus tissue of AD mice,and up-regulate the expression levels of Bcl-2.Conclusions SP has a protective effect on AD and the mechanism might be related to anti-oxidative stress an

关 键 词：大豆肽 阿尔茨海默病 氧化应激 凋亡 

分 类 号：R749.1[医药卫生—神经病学与精神病学]