鱼油联合锌硒对衰老模型小鼠学习记忆障碍及淀粉样前体蛋白酶解通路的保护作用  

THE PROTECTIVE EFFECT OF FISH OIL COMBINED WITH SELENIUM AND ZINC ON LEARNING AND MEMORY DEFICIT AND AMYLOID PRECURSOR PROTEIN PROCESSING IN AGED MICE

作　　者：付朝旭 许妍姬[1] FU Zhao-xu;XU Yan-ji(Department of Preventive Medicine,Medical College of Yanbian University,Yanji 133000,China)

机构地区：[1]延边大学医学院预防医学教研室,延吉133000

出　　处：《营养学报》2020年第1期56-60,共5页Acta Nutrimenta Sinica

基　　金：国家自然科学基金(No.81160159);吉林省中医药科技项目(No.2018-135);吉林省教育厅科学技术研究项目(No.吉教科合字2016-279号)。

摘　　要：目的探讨鱼油联合锌硒对衰老模型小鼠学习记忆障碍及淀粉样前体蛋白(amyloid precursor protein,APP)酶解通路的保护作用。方法在体外细胞实验中,用0.1μmol/L的二十碳五烯酸(EPA)、二十二碳六烯酸(DHA)、锌(Zn)、硒(Se)分别处理高分化的PC12细胞及APP695稳定转染的CHO细胞,共分为正常对照、抑制剂、EPA、DHA、EPA+DHA+Se、EPA+DHA+Se+Zn 6组。使用酶联免疫吸附测定方法(ELISA)测定细胞培养上清液中β、γ-分泌酶活性及Aβ1-40含量。在体内试验中,将60只两月龄雄性昆明小鼠随机分为正常对照、衰老、鱼油、鱼油+硒、鱼油+锌+硒及阳性对照6个组。连续腹腔注射200 mg/kg D-半乳糖建立衰老模型,采用ELISA法检测血清中β、γ-分泌酶活性;使用Morris水迷宫及跳台方法检测鱼油联合锌硒对衰老模型小鼠学习记忆障碍的保护作用。结果体外细胞实验显示,EPA、DHA处理组与正常对照组相比细胞上清液中β、γ-分泌酶活性受到抑制,Aβ1-40的含量降低;EPA、DHA、Zn、Se联合应用对细胞上清液中β、γ-分泌酶活性抑制作用增强。小鼠动物实验显示,与衰老组比较,鱼油、锌、硒处理组能够抑制血清β、γ-分泌酶活性;且鱼油联合锌硒抑制效果增强。行为学测试结果表明,鱼油联合锌硒缓解衰老模型小鼠学习记忆障碍。结论鱼油联合锌、硒对APP酶解通路具有较好的保护作用,并能减轻小鼠学习记忆障碍。Objective To study the potential effect of fish oil combined with selenium(Se)and zinc(Zn)on learning and memory deficit and amyloid precursor protein(APP)processing in aged mice.Methods In vitro cell experiments,highly differentiated PC12 cells were treated with 0.1μmol/L eicosapentaenoic acid(EPA),docosahexaenoic acid(DHA),Zn and Se,respectively.APP695 stably transfected CHO cells were divided into normal control,inhibitor,EPA,DHA,EPA+DHA+Se,EPA+DHA+Se+Zn groups.ELISA was used to detectβ,γ-secretase activity and Aβ1-40 content in cell culture supernatant.In vivo experiment,two month-old male Kunming mice were divided into six groups:normal control,aged,fish oil,fish oil+Se,fish oil+Se+Zn and positive control group.D-galactose(200 mg/kg)were injected intraperitoneally to establish an aged mice model.Serumβ-,γ-secretase activities were detected by ELISA.Morris water maze was used to detect the potential effect of fish oil combined with Se and Zn on learning and memory impairment in aged mice.Results Compared with the normal control group,the EPA and DHA treatment groups showed inhibitedβandγ-secretase activities,which affected the content of Aβ1-40.The results ofβ,γ-secretase activity in the supernatant of the cells showed that the inhibitory effect was enhanced when EPA,DHA,Zn and Se were combined.The results of ELISA analysis showed that fish oil,Zn and Se inhibited serumβandγ-secretase activities and fish oil combined with Zn and Se inhibited the most.Behavioral test results showed that fish oil combined with Zn and Se alleviated learning and memory impairment in aged mice.Conclusion Fish oil combined with Se and Zn is protective aganist the APP processing and alleviates the learning and memory deficit in aged mice.

关 键 词：二十碳五烯酸 二十二碳六烯酸 体外淀粉样前体蛋白 硒 锌 学习记忆 

分 类 号：R151.2[医药卫生—营养与食品卫生学]