目的 探讨β-淀粉样蛋白(Aβ)42介导的神经毒性对小脑2-氨基-3-羟基-5-甲基-4-异恶唑丙酸(AMPA)受体(AM-PAR)谷氨酸受体(GluR)2亚基及含半胱氨酸的天冬氨酸蛋白水解酶(caspase)-3蛋白和基因表达的影响.方法 Aβ425μl侧脑室注射制备阿尔茨海默病(AD)动物模型,利用水迷宫实验筛选入组SD大鼠.17 d后取材,将大鼠随机分为对照组(侧脑室注射5μl生理盐水)和Aβ42组,采用免疫组化染色、Western印迹和RT-PCR方法检测小脑AMPAR的GluR2亚基及caspase-3蛋白和基因的表达.结果 Aβ42组穿越平台次数显著低于对照组(P<0.05).Aβ42组GluR2亚基表达量及基因水平明显低于对照组(P<0.05),而caspase-3表达量及基因水平明显高于对照组(P<0.05).结论 Aβ42介导的神经毒性影响小脑AMPAR的GluR2亚基及caspase-3的表达,AMPAR通过caspase-3参与AD大鼠小脑中由Aβ42介导的神经毒性作用.%Objective To study the effect of neurotoxicity mediated byβ-amyloid protein 42 ( Aβ42 ) on expressions of cerebellar AMPA receptor (AMPAR) GluR2 subunit and caspase-3 protein and gene. Methods Alzheimer′s disease (AD) animal model was pre-pared by intracerebroventricular injection of Aβ42 (5μl), and water maze test was used to screen and enroll SD rats. Samples were random-ly divided into control ( intracerebroventricular injection of 5μl saline) and Aβ42 intracerebroventricular injection group, and the expressions of GluR2 subunit, caspase-3 protein and gene of cerebellum AMPAR were detected by immunohistochemical staining, Western blot and RT-PCR. Results The expressions of GluR2 subunit gene and protein in the Aβ42 intracerebroventricular injection group were significantly low-er than those of control group (P<0. 05). while the expression of caspase-3 was significantly higher than that of control group (P<0. 05), and the results of Western blot were consistent with the results of RT-PCR. Conclusions Neurotoxicity mediated by Aβ42 affects the expres-sions of GluR2 subunits and caspase-3 in cerebellar AMPAR, and AMPAR participates in the neurotoxicity mediated by Aβ42 in the cerebel-lum of rats with AD via caspase-3.
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