硒、锌对老年性痴呆模型小鼠APP酶解通路的保护作用及机制研究

发布时间：2018-02-21 16:37

本文关键词： 硒锌阿尔茨海默病 α、β、γ-分泌酶 Aβ- GSK-β Ph-tau 小鼠　出处：《营养学报》2017年02期 　论文类型：期刊论文

【摘要】：目的研究硒、锌对老年性痴呆(Alzheimer’s,AD)模型小鼠酶解通路的保护作用及机制。方法选用健康雄性2月龄昆明种小鼠60只,随机分为正常对照组(NC)、AD模型组、硒[Se,7.5μg/(kg bw)]+AD组、锌[Zn,5 mg/(kg bw)]+AD组、硒[Se,7.5μg/(kg bw)]+锌[Zn,5 mg/(kg bw)]+AD组、脑复康[Piracetam,230 mg/(kg bw)]+AD共6组,每组10只。连续60d腹腔注射D-半乳糖[150 mg/(kg bw)],建立老年性痴呆模型,采用酶联免疫吸附测定法(enzyme linked immunosorbent assay,ELISA)检测血清中α、β、γ-分泌酶含量以及脑组织中Aβ1-40含量;Western-blot法检测脑组织中糖原合成酶激酶-3β(GSK-3β)和磷酸化Tau(Ph-tau)蛋白水平。结果 ELISA法显示,与AD组比较,硒、锌可以增强α-分泌酶活性,抑制β、γ-分泌酶的活性,且硒锌联合作用增强,脑组织中Aβ_(1-40)含量明显降低。Western-blot法检测显示,与NC组比较,AD模型组GSK-3β、Ph-tau蛋白表达水平升高,而硒、锌处理组和硒锌联合作用组,GSK-3β、Ph-tau蛋白表达水平明显降低。结论硒、锌通过增加内源性α-分泌酶的活性,抑制β、γ-分泌酶的活性,减少Aβ_(1-40)的生成,降低GSK-3β、Ph-tau蛋白表达水平,可能对AD的发病及进展有一定预防保护作用。
[Abstract]:Objective to study the protective effect and mechanism of selenium and zinc on enzymatic pathway in mice with Alzheimer's disease (AD). Methods 60 healthy male 2 month old Kunming mice were randomly divided into three groups: normal control group, AD group, AD group and Zn [Zn5 mg/(kg bww] AD group. The Alzheimer's disease model was established by intraperitoneal injection of D-galactose (150 mg/(kg BW) for 60 days in 6 AD groups, 10 rats in each group, and 10 rats in each group in the AD group [Zn5 mg/(kg BW] and Piracetamol 230 mg/(kg bww, respectively, for 60 consecutive days, in order to establish the Alzheimer's disease model, and to establish the model of Alzheimer's disease by intraperitoneal injection of D-galactose (150 mg/(kg BWW) for 60 days. The levels of 伪, 尾, 纬 -secretory enzymes in serum and A 尾 _ 1-40 in brain tissue were detected by enzyme linked immunosorbent assayayesis-ELISA-Western-blot method was used to detect the protein levels of glycogen synthase kinase -3 尾 -PhosphorylTau-Ph-tau.Results compared with AD group, the levels of se, se, Tau-tau-tauprotein were detected by ELISA. Zinc could increase the activity of 伪 -secretase, inhibit the activity of 尾, 纬 -secretase, and increase the combined effect of selenium and zinc. The content of A 尾 -tir 1-40) in brain tissue was significantly decreased. Western-blot assay showed that the expression of GSK-3 尾 -Ph-tau protein in AD model group was higher than that in NC group. Conclusion the level of GSK-3 尾 -Ph-tau protein in zinc treated group and Se-Zn combined treatment group was significantly decreased. Conclusion selenium and zinc can inhibit the activity of 尾, 纬 -secretase, reduce the production of A 尾 -1-40) and decrease the expression level of GSK-3 尾 -Ph-tau protein by increasing the activity of endogenous 伪 -secretase, reducing the activity of 尾, 纬 -secretase, and decreasing the expression level of GSK-3 尾 -Ph-tau protein. It may have a preventive and protective effect on the pathogenesis and progression of AD.
【作者单位】：延边大学医学院预防医学教研室;
【基金】：吉林省教育厅科学技术研究项目(吉教科合字2016-279号)
【分类号】：R-332;R749.16

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