自噬对血管性痴呆大鼠海马CA1区突触素及突触后膜致密物质95表达的影响

目的 探讨自噬对血管性痴呆大鼠海马CA1区突触素(synaptophysin,Syn)及突触后膜致密物质95(postsynaptic density material 95,PSD-95)表达的影响.方法 健康雄性SD大鼠96只,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、2、4、8周4个亚组,每个亚组6只大鼠.应用改良的Pulsinelli四血管阻断法制备血管性痴呆模型,采用蛋白质印迹法检测大鼠海马CA1区微管相关蛋白1轻链3(LC3)、Syn、PSD-95蛋白表达.结果 (1)与Sham组比较,VD组各时间点LC3-Ⅱ/LC3-Ⅰ比值增加,Syn、PSD-95蛋白表达均减少,差异有统计学意义(P均＜0.01);与VD组比较,3-MA组各时间点LC3-Ⅱ/LC3-Ⅰ比值减少,Syn、PSD-95蛋白表达增加(P＜0.05或P＜0.01),Rap组各时间点LC3-Ⅱ/LC3-Ⅰ比值增加,Syn、PSD-95蛋白表达降低(P均＜0.01).(2)自噬相关蛋白LC3-Ⅱ/LC3-Ⅰ比值与Syn、PSD-95蛋白表达呈负相关(P均＜0.01).结论 自噬对血管性痴呆大鼠海马CA1区突触可塑性相关蛋白Syn、PSD-95表达具有抑制作用,抑制自噬有利于血管性痴呆大鼠海马CA1区神经突触重塑.

Effect of autophagy on expression of synaptophysin and postsynaptic density material 95 in CA1 hippocampal region of vascular dementia rats

Objective To explore the effect of autophagy on the expression of synaptophysin (Syn) and postsynaptic density material 95 (PSD-95) in CA1 hippocampal region of vascular dementia rats.Methods A total of 96 healthy male SD rats were randomly divided into sham operation group (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 further randomized into 4 subgroups 1,2,4 and 8 weeks after model establishment.The rat model of vascular dementia was established using a modified Pulsinelli four-vessel occlusion method.The expressions of Syn and PSD-95 in CA1 hippocampal region of the vascular dementia rats were detected by Western blotting analysis.Results (1) Compared with the Sham group,the ratio of LC3-Ⅱ/LC3-Ⅰ in CA1 hippocampal region of the vascular dementia rats was significantly increased and the expressions of Syn and PSD-95 were significantly decreased in VD group at different time points (all P＜0.01).Compared with the VD group,the ratio of LC3-Ⅱ/LC3-Ⅰ was significantly decreased and the expressions of Syn and PSD-95 were significantly increased in 3-MA group at different time points (P＜0.05 or P＜0.01);the ratio of LC3-Ⅱ/LC3-Ⅰ was significantly increased and the expression of Syn and PSD-9 5 were significantly decreased in Rap group at different time points (all P＜0.01).(2) Correlation analysis showed that the ratio of LC3-Ⅱ/LC3-Ⅰ was negatively correlated with Syn and PSD-95 expression (all P＜0.01).Conclusion Autophagy may inhibit the expression of synaptic plasticity related proteins,Syn and PSD-95,in CAl hippocampal region of the vascular dementia rats,and suppressing autophagic activity is benefitial to the synaptic plasticity.