| 摘要: |
| 目的 观察血管性痴呆(vascular dementia,VD)模型大鼠海马CA1区自噬及微管相关蛋白1轻链3 (microtubule-associated protein 1 light chain 3,MAP1LC3,LC3)的表达,探讨自噬在血管性痴呆发病中的可能作用。方法 大鼠随机分为假手术组(sham组)、血管性痴呆模型组(VD组)和Wortmannin自噬抑制剂组(WM组),每组又随机分为模型制备后1、2、4、8、12周5个亚组。采用四血管阻断法制作血管性痴呆模型,Morris水迷宫法检测学习记忆能力,透射电镜观察自噬体的形成,蛋白质印迹法检测LC3Ⅱ/LC3Ⅰ 的比值作为自噬活性的指标。结果 与假手术组相比,VD组大鼠平均逃避潜伏期延长(P<0.05或0.01),穿越平台次数减少(P<0.05或0.01)；与VD组比较,WM组大鼠逃避潜伏期缩短(P<0.05或0.01),穿越平台次数增加(P<0.05或0.01)。VD组大鼠海马CA1区1周时神经细胞核膜凹陷,胞核浓缩,线粒体肿胀,可见自噬体、溶酶体;4周时自噬体、溶酶体数量显著增多;12周时仍可见自噬体。WM组神经元损伤较VD组减轻,自噬体数量减少。VD组大鼠海马CA1区LC3Ⅱ/LC3Ⅰ比值在1周时升高,4周时达到高峰,8周时开始下降,12周时仍较高。WM组各时间点LC3Ⅱ/LC3Ⅰ比值较VD组低,差异有统计学意义(P<0.05或0.01)。结论 血管性痴呆大鼠海马CA1区自噬活性被激活,可能参与了血管性痴呆的发生发展。 |
| 关键词: 血管性痴呆 海马 自噬 微管相关蛋白1轻链3 |
| DOI： |
| 投稿时间：2013-01-14修订日期：2013-06-23 |
| 基金项目:河北省高等学校科学技术研究重点项目(ZH2012046). |
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| Expression of autophagy and microtubule-associated protein 1 light chain 3 in hippocampus CA1 area of vascular dementia rats |
| LIU Bin*,TANG Jing,YUAN Min,LI Shi-ying |
(First Department of Neurology, the Affiliated Hospital of Hebei United University, Tangshan 063000, Hebei, China
*Corresponding author.) |
| Abstract: |
| Objective To observe the expression of autophagy and microtubule-associated protein 1 light chain 3 (LC3) in hippocampus CA1 area of vascular dementia rats, so as to explore the role of autophagy in the pathogenesis of vascular dementia. Methods The rats were randomly divided into sham operation group, vascular dementia model group (VD group) and Wortmannin autophagy inhibitor group (WM group). Each group was further divided into 1, 2, 4, 8 and 12 week subgroups after the successful model preparation (n=6). Vascular dementia rat models were established by blocking four vessels. The learning and memory abilities were examined by Morris water maze, autophagy was observed by transmission electron microscope, and the ratio of autophagy-associated protein LC3Ⅱ/LC3Ⅰ was obtained by Western blotting analysis. Results Compared with the sham operation group, the escape latency was signficantly increased in the VD group（P<0.05 or P<0.01）, and the times of traversing terrace were significantly decreased (P<0.05 or P<0.01). Compared with the VD group, the escape latency was significantly decreased and the times of traversing terrace was significantly increased in WM group (P<0.05 or P<0.01). In the hippocampus CA1 area of VD group, the nuclear membrane of neurons was sagged, the nuclei was condensed, mitochondria were swollen, and autophagosomes and lysosomes were observed in week 1; the autophagosomes and lysosomes were increased in week 4, and they could still be found in week 12. The neuronal damage was slighter and the autophagosomes were reduced in WM group compared with VD group. In CA1 area of hippocampus of VD group, the LC3Ⅱ/LC3Ⅰ ratio was increased in week 1, peaked in week 4, began to decline in week 8, and still kept at a high level in week 12. Compared with the VD group, the LC3Ⅱ/LC3Ⅰ ratio was significantly decreased in WM group at all time points (P<0.05 or P<0.01).Conclusion Autophagy is activated in CA1 area of hippocampus of VD rats, and may play an important role in the pathogenesis of VD. |
| Key words: vascular dementia hippocampus autophagy microtubule-associated protein 1 light chain 3 |
