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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
刘斌*,刘金霞,毛文静,张文彦,邓春颖,张晋霞,马原源,贺永贵,李世英
0
(华北理工大学附属医院神经内一科, 唐山 063000
*通信作者)
摘要:
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。
关键词:  血管性痴呆  自噬  突触素  突触后膜致密物质95  突触可塑性
DOI:10.16781/j.0258-879x.2017.02.0206
投稿时间:2016-06-13修订日期:2016-11-25
基金项目:河北省高等学校科学技术研究重点项目(ZH2012046),河北省重大医学科研课题(zd2013087).
Effect of autophagy on expression of synaptophysin and postsynaptic density material 95 in CA1 hippocampal region of vascular dementia rats
LIU Bin*,LIU Jin-xia,MAO Wen-jing,ZHANG Wen-yan,DENG Chun-ying,ZHANG Jin-xia,MA Yuan-yuan,HE Yong-gui,LI Shi-ying
(First Department of Neurology, Affiliated Hospital of North China University of Science and Technology, Tangshan 063000, Hebei, China
*Corresponding author)
Abstract:
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-95 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 CA1 hippocampal region of the vascular dementia rats, and suppressing autophagic activity is benefitial to the synaptic plasticity.
Key words:  vascular dementia  autophagy  synaptophysin  postsynaptic density material 95  synaptic plasticity