目的 研究不同膳食锌含量对成年APPswe／PSEN1dE9双转基因阿尔茨海默病模型小鼠大脑内锌相关转运体mRNA表达的影响.方法 成年APPswe/PSEN1dE9双转基因小鼠[J004462 B6C3-T9(APPswe,PSEN1dE9)85D60/J]33只,随机分为膳食锌缺乏组1(ZD1)、膳食锌缺乏组2(ZD2)、膳食补锌组(ZS)和阳性对照组(PC),及10只正常对照组(NC),应用RT-PCR方法检测小鼠大脑中ZnT-1、MT1和ZIP1 mRNA的表达;原子吸收分光光度法测定血清锌浓度.结果 PC中ZnT-1表达较NC有显著性升高(P＜0.01).MT1和ZIP1在PC和NC中表达无显著差异.缺锌喂养后,ZnT-1的表达与PC组比有显著下降(P＜0.01),下降随缺锌时间的延长而加剧,补锌后ZnT-1表达有所上升,存在着时间-反应关系和剂量-反应关系.缺锌喂养50 d后,大脑中MT1与ZIP1 mRNA表达并无明显改变,但持续缺锌喂养至80 d后,mRNA表达均明显下降(P＜0.01),补锌喂养可恢复至缺锌前水平.结论 成年APPswe/PSEN1dE9双转基因小鼠大脑内存在着ZnT-1的异常高表达,膳食锌缺乏可下调大脑内ZnT-1、MT1、2IP1的mRNA表达.%Objective To investigate the effect of dietary zinc deficiency on the mRNA expression of ZnT-1, MT1 and ZIP1 in the brain of mice with Alzheimer's disease. Methods Thirty three adult APPswe/PSEN1dE9 double transgenic mice(Alzheimer's disease model) were randomly divided into dietary zinc deficiency group 1 (ZD1, n = 10) , dietary zinc deficiency group 2( ZD2, n = 10) , dietary zinc supplement group (ZS, n = 8) and the positive control group (PC, n =5) , with 10 normal mice as a negative control( NC). ZnT-1, MT1 and ZIP1 mRNA expression in the brain were detected by RT-PCR. Results ZnT-1 mRNA expression was significantly increased in group PC compared with group NC(P <0.01), MT1 and ZIP1 mRNA expression in the group PC and group NC had no significant differences. Compared to group PC, ZnT-1 expression was significantly decreased in group ZD1 and more markedly decreased in group ZD2 ( P < 0. 01). The expression of ZnT-1 mRNA was increased with the amount of dietary zinc supplemented in a time- and dose-response manner. There were no significant changes of MT1 and ZIP1 mRNA expression in groups ZD1 and PC; but the expression of MT1 and ZIP1 mRNA was significantly decreased in group ZD2 after 80 days of feeding with zinc deficiency diet(P <0.01). Conclusion ZnT-1 mRNA is up-regulated in the brain of adult APPswe/ PSENldE9 double transgenic mice, and dietary zinc supplement can down-regulate the expression of ZnT-1, MT1 and ZIP1 mRNA in the brain.
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