TXNIP介导的氧化应激在雌激素延缓阿尔兹海默病中的作用  

Role of TXNIP-mediated oxidative stress in delaying Alzheimer’s disease by estrogen

作　　者：潘琼[1] 郭科[2] 李亚倩 涂秋云[3] PAN Qiong;GUO Ke;LI Yaqian;TU Qiuyun(Department of Obstetrics and Gynecology,Third Xiangya Hospital,Central South University,Changsha 410013,China;Department of Neurology,Third Xiangya Hospital,Central South University,Changsha 410013,China;Department of Geriatrics,Third Xiangya Hospital,Central South University,Changsha 410013,China)

机构地区：[1]中南大学湘雅三医院妇产科,长沙410013 [2]中南大学湘雅三医院神经内科,长沙410013 [3]中南大学湘雅三医院老干科,长沙410013

出　　处：《中南大学学报（医学版）》2019年第12期1360-1366,共7页Journal of Central South University ：Medical Science

基　　金：国家自然科学基金(81671398);湖南省自然科学基金(2019JJ50912)~~

摘　　要：目的:研究硫氧还蛋白相互作用蛋白(thioredoxin-interacting protein,TXNIP)在阿尔茨海默病(Alzheimer’s disease,AD)发病及雌激素延缓AD发生中的作用。方法:检测雌二醇(E2)处理的AD细胞模型中活性氧(reactive oxygen species,ROS)和TXNIP水平、细胞凋亡情况;TXNIP过表达慢病毒后,观察E2处理对AD细胞ROS水平和凋亡的影响。在AD大鼠模型中,观察E2处理后大鼠学习记忆能力和TXNIP的表达变化;过表达TXNIP后,观察E2处理对AD大鼠模型学习记忆能力的影响。结果:AD细胞中ROS,TXNIP及细胞凋亡水平升高,而E2处理可降低AD细胞ROS,TXNIP及细胞凋亡水平;增强TXNIP表达后,E2处理可降低AD细胞ROS和凋亡水平。与细胞实验类似,E2处理可增强AD大鼠的学习记忆能力,抑制脑内TXNIP表达;而TXNIP过表达可削弱E2对AD大鼠学习记忆能力的增强效果。结论:雌激素可通过抑制神经组织中TXNIP的表达,降低神经损伤程度,延缓AD的发生发展。Objective:To study the functional mechanism of thioredoxin-interacting protein (TXNIP) in delaying Alzheimer’s disease (AD) by estrogen.Methods:After estradiol (E2) treatment in Aβ-induced AD cell model,reactive oxygen species (ROS),TXNIP,and apoptosis levels were detected.After lentiviral infection with TXNIP overexpression,the effect of E2 on ROS and apoptosis were observed.In the AD rat model,the learning and memory ability and the expression of TXNIP in the hippocampus were observed in the presence of E2.After overexpressing TXNIP,the effect of E2 on the learning and memory ability of AD rat model was observed.Results:ROS,TXNIP and apoptosis levels were enhanced in AD cell model,while E2 treatment reduced ROS,TXNIP and apoptosis levels in AD cell model.After enhancing TXNIP,E2 treatment reduced ROS and apoptosis levels in AD cell model.Similar to the cell experiment,E2 enhanced the learning and memory ability in the AD rat model and inhibited the expression of TXNIP in brain,while TXNIP overexpression attenuated the effect of E2 on learning and memory ability in the AD rats.Conclusion:Estrogen can inhibit the expression of TXNIP in nerve tissue,reduce nerve damage,and delay the development of AD.

关 键 词：阿尔茨海默病 神经损伤 雌激素 硫氧还蛋白相互作用蛋白 活性氧 

分 类 号：R749.16[医药卫生—神经病学与精神病学]