自噬对血管性痴呆大鼠海马CA1区生长相关蛋白-43及微管相关蛋白-2表达的影响

Effects of Autophagy on Expression of Growth- associated Protein- 43 and Microtubule Associated Protein- 2 in CA1 Area of Hippocampus of Vascular Dementia Rats

目的探讨自噬对血管性痴呆大鼠海马CA1区突触可塑性相关蛋白生长相关蛋白-43(GAP-43)和微管相关蛋白-2(MAP-2)表达的影响。方法 96只健康雄性Sprague-Dawley大鼠,随机分为假手术组(Sham组)、血管性痴呆模型组(VD组)、自噬抑制剂3-甲基腺嘌呤预处理组(3-MA组)和自噬激动剂雷帕霉素预处理组(Rap组)。每组又分为模型制备成功后1周、2周、4周、8周四个亚组,每个亚组6只。应用改良Pulsinelli四血管阻断法制备血管性痴呆模型。采用免疫组化法检测大鼠海马CA1区GAP-43、MAP-2蛋白的表达。结果与Sham组比较,VD组各时间点GAP-43蛋白表达明显增加(P<0.01),MAP-2蛋白表达明显减少(P<0.01);与VD组比较,3-MA组各时间点GAP-43、MAP-2蛋白表达水平增加(P<0.05),Rap组各时间点GAP-43、MAP-2蛋白表达水平降低(P<0.05)。结论自噬抑制血管性痴呆大鼠海马CA1区突触可塑性相关蛋白GAP-43、MAP-2表达,抑制自噬可能有利于血管性痴呆大鼠海马CA1区神经突触重塑。

Objective To observe the effects of autophagy on the expression of synaptic plasticity related protein, growth-associated protein-43（GAP-43） and microtubule associated protein-2（MAP-2）, in CA1 area of hippocampus of vascular dementia rats. Methods Ninety-six healthy male Sprague-Dawley rats were randomly divided into sham group, vascular dementia model group（VD group）, autophagy inhibitor 3-methyl adenine preconditioning group（3-MA group） and autophagy agonist rapamycin preconditioning group（Rap group）. Each group was divided randomly into subgroups of one week, two weeks, four weeks and eight weeks after modeling, six rats in each group. The vascular dementia rat model was established with modified Pulsineli＇s four-vessel occlusion. The expression of GAP-43 and MAP-2 in CA1 area of hippocampus were detected with immunohistochemistry. Results Compared with the sham group, the expression of GAP-43 protein increased, and the expression of MAP-2 protein decreased at every time point in VD group（P〈0.01）. Compared with VD group, the expression of both GAP-43 and MAP-2 increased in 3-MA group（P〈0.05）, and decreased in Rap group（P〈0.05）. Conclusion Autophagy may inhibit the expression of synaptic plasticity related protein, GAP-43 and MAP-2, in CA1 area of hippocampus in vascular dementia rats, indicating inhibition of autophagy may promote synaptic remodeling.