槲皮素通过抑制氧化应激改善3×Tg-AD小鼠的认知功能障碍  

Quercetin Ameliorates Cognitive Dysfunction in 3×Tg-AD Mice by Inhibiting Oxidative Stress

作　　者：杨宜歆 时磊[1] 赵杨[1] 王延虹[1] 李艳艳[1] Yang Yixin;Shi Lei;Zhao Yang;Wang Yanhong;Li Yanyan(The Fifth Affiliated Hospital of Zhengzhou University,Zhengzhou 450052,China)

机构地区：[1]郑州大学第五附属医院,郑州450052

出　　处：《世界科学技术-中医药现代化》2022年第4期1642-1649,共8页Modernization of Traditional Chinese Medicine and Materia Medica-World Science and Technology

摘　　要：目的探讨槲皮素(Quercetin,QT)对含有3个突变等位基因(PS1、APP、Tau)的纯合子小鼠(3×Tg-AD)的认知功能改善作用及其机制。方法通过基因鉴定确定小鼠的基因型,将9月龄的3×Tg-AD小鼠和其同窝野生对照小鼠随机分为4组:野生型组(wildtype,WT)、野生型+QT组(WT+QT)、模型组(3×Tg-AD)和模型小鼠+QT组(3×Tg-AD+QT),每组8只。WT+QT组和3×Tg-AD+QT组的小鼠灌胃给予QT 15 mg/kg/天,WT组和3×Tg-AD组的小鼠灌胃给予等体积溶剂,共治疗8周。第7周进行水迷宫实验检测小鼠的学习记忆能力。采用ELISA法检测小鼠脑组织中的肿瘤坏死因子-α(tumor necrosis factor-α)、白介素-1β(interleukin-1β)和小鼠血清中谷胱甘肽-过氧化物酶(glutathione peroxidase,GSH-Px)的含量;试剂盒检测小鼠血清中丙二醛(malondialdehyde,MDA)和总超氧化物歧化酶(superoxide dismutase,SOD)的含量以及脑组织中一氧化氮(nitric oxide,NO)的含量;Western blot检测脑组织中核转录因子E2相关因子2和Kelch样环氧氯丙烷相关蛋白1的表达水平。结果3×Tg-AD组小鼠存在明显的认知功能障碍;而3×Tg-AD+QT组小鼠的学习记忆能力明显提高(P<0.05)。另外,3×Tg-AD组血清中MDA水平较WT组升高,SOD与GSH-Px水平较WT组下降;3×Tg-AD+QT组小鼠血清中MDA水平下降,SOD和GSH-Px水平则升高。3×Tg-AD组小鼠脑组织中的NO、TNF-α、IL-1β水平明显升高;3×Tg-AD+QT组小鼠脑组织中的炎症因子水平均明显降低(P<0.05)。3×Tg-AD组小鼠脑组织中的Nrf2表达降低,Keap1表达升高;3×Tg-AD+QT组中,Nrf2表达上调,Keap1表达下调(P<0.05)。结论QT可能通过抑制炎症因子和MDA,Keap1的水平,上调SOD,GSH-Px,Nrf2的表达,发挥改善3×Tg-AD小鼠学习记忆能力的作用。Objective To investigate the effect of Quercetin(QT)on cognitive function improvement and its mechanism in 3×Tg-AD mice containing 3 mutant alleles(PS1,APP,Tau).Methods All the experimental mice were genotyped.9-month-old 3×Tg-AD mice and their wild-type littermates were randomly divided into 4 groups:wild-type group(WT),wild-type+QT group(WT+QT),model group(3×Tg-AD)and model mice+QT group(3×Tg-AD+QT),with 8 mice in each group.Mice in WT+QT group and 3×Tg-AD+QT group were intragastrically administrated with QT(15 mg/kg/d)and mice in WT group and 3×Tg-AD group were given equal volume of solvent for 8 weeks.At week 7,water maze test was conducted to test the learning and memory ability of mice.TNF-αand IL-1βin mouse brain tissue were detected by ELISA.Serum levels of GSH-Px,MDA,SOD and the level of NO in mouse brain were also measured.The expression levels of Nrf2 and Keap1 in brain tissues were detected by Western blot.Results 3×Tg-AD mice had obvious cognitive dysfunction compared with WT mice.Short-term learning ability and spatial memory of mice in 3×Tg-AD+QT group were significantly improved compared to that of 3×Tg-AD mice(P<0.05).In addition,higher serum MDA,lower serum SOD and GSH-Px were detected in 3×Tg-AD group compared with WT mice,which could be restored by the administration of QT in 3×Tg-AD mice.Compared with WT group,the levels of NO,TNF-αand IL-1βin brain tissues of 3×Tg-AD mice were significantly increased.The administration of QT was demonstrated to reduce the levels of NO,TNF-αand IL-1βin brain tissues of model mice(P<0.05).Moreover,QT was displayed to increase the expression of Nrf2 and decrease Keap1 expression in brain tissues of 3×Tg-AD group(P<0.05),which restored the levels of both Nrf2 and Keap1 to the similar levels of WT mice.Conclusion QT may improve the learning and memory ability of 3×Tg-AD mice by inhibiting the levels of inflammatory factors(MDA and Keap1)and up-regulating the expressions of SOD,GSH-Px and Nrf2.

关 键 词：阿尔茨海默病 3×Tg-AD小鼠 槲皮素 氧化应激 

分 类 号：R285.5[医药卫生—中药学]