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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 |
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(华北理工大学附属医院神经内一科, 唐山 063000
*通信作者) |
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| 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）. |
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| 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 |
