Aβ42介导的阿尔茨海默病对小脑AMPA受体GluR2亚基及caspase-3表达的影响

Effect of neurotoxicity mediated by Aβ42 on expressions of cerebellar AMPA receptor GluR2 subunit and caspase-3

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(AMPAR)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 Aβ42 5μl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 prepared by intracerebroventricular injection of Aβ42（ 5 μl）,and water maze test was used to screen and enroll SD rats. Samples were randomly divided into control（ intracerebroventricular injection of 5 μl 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 RTPCR.Results The expressions of GluR2 subunit gene and protein in the Aβ42 intracerebroventricular injection group were significantly lower 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 expressions of GluR2 subunits and caspase-3 in cerebellar AMPAR,and AMPAR participates in the neurotoxicity mediated by Aβ42 in the cerebellum of rats with AD via caspase-3.