沙利度胺对Aβ_(1-42)致AD模型小鼠的海马蛋白质组学影响  

The hippocampal proteomics mechanism of thalidomide in Alzheimer’s disease model mice induced by Aβ_(1-42)

作　　者：吴宿慧[1] 张晗[1] 张宇航[1] 牛婷媛 李寒冰[1] 高剑峰[1] 李根林[1] WU Su-hui;ZHANG Han;ZHANG Yu-hang;NIU Ting-yuan;LI Han-bing;GAO Jian-feng;LI Gen-lin(Henan University of Chinese Medicine,Henan Zhong-jing Recipe Health and Aging Industry Engineering Research Center,Zhengzhou 450046,China)

机构地区：[1]河南中医药大学,河南省仲景方药健康衰老产业工程研究中心,河南郑州450046

出　　处：《中国药理学通报》2023年第2期315-325,共11页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No 81503363)。

摘　　要：目的观察沙利度胺对阿尔茨海默病(Alzheimer’s disease,AD)小鼠学习、记忆功能改变和海马组织蛋白质组的影响,筛选沙利度胺防治AD的差异蛋白及调控途径,探讨其可能机制。方法将实验小鼠随机分成空白对照组、模型组和沙利度胺高、低剂量组。每日灌胃给药,共持续21 d。给药后,通过Morris水迷宫实验评估小鼠的学习记忆能力,HE、尼氏染色考察小鼠海马的病理组织学形态,ELISA法检测小鼠脑内线粒体呼吸链酶复合物的活性,应用Label-free蛋白组学筛选各组海马蛋白质组差异表达。结果水迷宫结果表明,与模型组相比,给药组的逃避潜伏期时间明显减少,且穿越平台次数明显提高(P<0.05)。沙利度胺给药治疗可改善海马区神经元形态结构,并可提高AD小鼠脑组织线粒体呼吸链复合物Ⅰ、Ⅱ、Ⅳ、Ⅴ的活性(P<0.05);共鉴定出4378个差异性蛋白质,对AD小鼠海马组织中580个蛋白表达有明显调节作用(P<0.05),可能共同参与调节神经变性途径-多种疾病和阿尔茨海默病等通路发生改变。结论沙利度胺对Aβ_(1-42)诱导的AD模型小鼠的学习记忆功能有效改善,有线粒体保护功能,对由AD引起的差异蛋白质表达有调节作用。Aim To observe the effect of thalidomide on the learning and memory ability and hippocampal tissue proteome of Alzheimer’s disease(AD)mice,to screen the differential proteins of thalidomide in preventing and treating AD,the pathways involved in regulation,and to explore its possible mechanism.Methods The experimental mice were randomly divided into blank control group,model group,and thalidomide high and low dose groups.The drugs were administered by gavage every day for 21 days.After the administration,Morris water maze test was used to evaluate the learning and memory abilities of the mice,HE staining and Nissl staining were used to observe the pathological tissue morphology of the mouse hippocampus,ELISA was employed to detect the mitochondrial respiratory chain enzyme complex in mouse brain,and the Label-free proteomics method was used to screen different groups of hippocampal proteome proteins.Results The results of the Morris water maze showed that compared with the model group,the escape latency time of the drug group was significantly reduced,and the number of crossing the platform significantly increased(P<0.05).Thalidomide administration could improve the morphological structure of neurons in hippocampus,and could increase the activity of the mitochondrial respiratory chain complexⅠ,Ⅱ,ⅣandⅤof the brain tissues of AD mice(P<0.05).A total of 4378 differential proteins were identified,which had a significant regulatory effect on the expression of 580 proteins in hippocampus of AD mice(P<0.05).Energy metabolism may jointly participate in the regulation of neurodegeneration pathways-changes in pathways such as various diseases and Alzheimer’s disease.Conclusions Thalidomide can significantly improve the learning and memory function of AD model mice induced by Aβ_(1-42).It has mitochondrial protection,exerting a regulatory effect on the differential protein expression caused by AD.

关 键 词：阿尔茨海默病 海马 线粒体 差异蛋白 蛋白组学 生物学信息分析 

分 类 号：R-332[医药卫生] R322.81R329.24R341R745.7