β-细辛醚对APPswe/PS1dE9双转基因小鼠脑组织中差异蛋白表达的影响  

Effect of β-asarone on differential protein expression in brain tissue of APPswe/PS1dE9 double transgenic mice

作　　者：郭莉莉[1,2] 王豫君 敖俊文 郭艳丽 GUO Li-li;WANG Yu-jun;AO Jun-wen;GUO Yan-li(Department of Pathology, The Second Hospital Affiliated to Guiyang University of Chinese Medicine, Guiyang 550002, Guizhou, China;Department of Pathology, The First People’s Hospital of Guiyang, Guiyang 550002, Guizhou, China;Department of Pathology, School of Basic Medicine, Guizhou Medical University, Guiyang 550004, Guizhou, China)

机构地区：[1]贵阳中医学院第二附属医院病理科,贵阳550002 [2]贵阳市第一人民医院病理科,贵阳550002 [3]贵州医科大学基础医学院病理学教研室,贵阳550004

出　　处：《第二军医大学学报》2017年第10期1286-1292,共7页Academic Journal of Second Military Medical University

基　　金：国家自然科学基金(30870986);贵州省科教青年英才培养工程项目[黔省专合字(2012)197号];贵州省科学技术基金[黔科合J字(2012)2091号]~~

摘　　要：目的观察β-细辛醚对APPswe/PS1dE9双转基因小鼠脑组织中差异蛋白表达的调节作用,探讨其对阿尔茨海默病(Alzheimer disease,AD)的治疗作用机制。方法实验动物分为正常对照组(C57BL/6J小鼠)、模型组(APPswe/PS1dE9小鼠)和β-细辛醚治疗组(APPswe/PS1dE9小鼠),每组10只。β-细辛醚治疗组用灌胃方法给药,正常对照组和模型组给予等量生理盐水,历时90d。用Morris水迷宫行为学方法测试小鼠学习记忆能力,用免疫组织化学方法检测小鼠脑组织中β-淀粉样前体蛋白(APP)的表达。用同位素标记相对和绝对定量(iTRAQ)技术对小鼠脑组织进行蛋白质组学分析,用蛋白质印迹法鉴定差异蛋白H2A、H2B的表达。结果与模型组小鼠比较,经β-细辛醚治疗后,小鼠的逃避潜伏期和第1次穿越平台时间缩短(P<0.05),平台穿越次数增多(P<0.05),APP的表达减少(P<0.05),差异蛋白组蛋白H2A1-H、H2B2-E和H2B1-F/J/L的表达水平下降(P<0.05)。结论β-细辛醚能够介入到组蛋白的修饰过程而起到治疗作用,这可能是其改善β-淀粉样肽毒性所致学习记忆能力下降的机制之一。ObjectiveTo investigate the effect ofβ-asarone on differential protein expression in brain tissue of APPswe/PS1dE9double transgenic mice,and to explore its mechanism in treatment of Alzheimer disease(AD).MethodsThe animals were divided into normal control group(C57BL/6J mice),model group(APPswe/PS1dE9mice)andβ-asarone treatment group(APPswe/PS1dE9mice),with ten mice in each group.In a period of90days,the mice inβ-asarone treatment group were administered withβ-asarone by intragastric gavage(15mg/[kg·d]),and the mice in normal control and model groups were administered with equal doses of normal saline.The learning and memory abilities of mice were detected by Morris water maze test.The expression ofβ-amyloid precursor protein(APP)in brain tissues was detected by immunohistochemistry.Proteomics analysis of brain tissues was performed by isobaric tags for relative and absolute quantification(iTRAQ).The expression of differential protein H2A and H2B was identified by Western blotting.ResultsCompared with the model group,the escape latency and the first latency time required to find the escaped platform of mice in theβ-asarone treatment group were significantly shortened(P<0.05),the across platform times were significantly increased(P<0.05),the expression of APP was significantly decreased(P<0.05),and the expressions of H2A-1-H,H2B-2-E and H2B1F/J/L were significantly decreased(P<0.05).Conclusionβ-Asarone plays a therapeutic role by intervening the modification of histone,which might be one of the mechanisms to improve learning and memory abilities injured by the toxicity ofβ-amyloid peptide.

关 键 词：阿尔茨海默病 Β-细辛醚 双转基因小鼠 组蛋白类 蛋白质修饰 

分 类 号：R749.16[医药卫生—神经病学与精神病学]