中文摘要：

目的通过对血管痴呆（vascular dementia,VD）模型大鼠行为学、免疫组化及蛋白质组学研究,探讨VD病理生理机制,揭示其背后隐含的关键神经生物分子。方法双侧颈总动脉结扎（2-VO法）建立VD大鼠模型,随机分为假手术组、VD模型组,Morris水迷宫评价大鼠的空间学习记忆能力;免疫组化方法检测海马脑区tau蛋白、p-tau蛋白、Aβ淀粉样蛋白表达量的改变;蛋白质组学技术分析鉴定VD模型中差异表达蛋白改变。结果（1）Mories水迷宫实验证实术后1、2、3、4、5 d VD组大鼠逃避潜伏期明显延长（82.7±22.3、82.2±25.1、71.5±31.7、68.3±9.2、60.2±18.9）,与假手术组相比差异明显,有统计学意义（P〈0.01,P〈0.05）;（2）VD组大鼠海马脑区Tau蛋白、P-Tau蛋白、Aβ淀粉样蛋白表达量显著上升（3.75±0.94、5.16±1.02、3.65±1.21）,与假手术组相比差异显著,有统计学意义（P〈0.05）;（3）与假手术组相比,VD模型组共筛选发现21个差异蛋白点,质谱最终鉴定出4种蛋白表达上调,分别是α-烯醇化酶、硫氧还原蛋白、丝裂原活化蛋白激酶激酶1、二氢嘧啶酶相关蛋白;1种蛋白表达下调,即谷胱甘肽合成酶。结论 2-VO法成功制备了VD大鼠模型;蛋白质组学技术发现VD发病过程中关键蛋白。对详细阐述VD发病机制及VD治疗中可能的蛋白靶点提供理论依据和思路线索。

英文摘要：

Objective To investigate the molecular pathological mechanism of vascular dementia（ VD）,behavioral study,immunohistochemistry and proteomics technology were used in our experiment. Methods Bilateral common carotid artery ligation（ 2-VO） method was used to establish VD rats model,rats were randomly divided into sham-operation group and VD model group. Morris water maze was used to evalue the spatial learning; Tau protein,p-tau protein,Aβamyloid protein expression in hippocampus brain regions were detected by immunohistochemistry; differentially expressed proteins were analysed and identificed by Proteomics analysis. Results（ 1） The Mories water maze experiment confirmed the escape latent period were obviously prolonged（ 82. 7 ± 22. 3,82. 2 ± 25. 1,71. 5 ± 31. 7,68. 3 ± 9. 2,60. 2 ± 18. 9） after the operation1,2,3,4,5 day,which were significant different compaed with the control group（ P 〈0. 01,P 〈0. 05）;（ 2） Tau,P-Tau,Aβamyloid protein expression in hippocampus brain regions of VD rat marked increased（ 3. 75 ± 0. 94,5. 16 ± 1. 02,3. 65 ±1. 21）,the difference were significant compared with control group（ P 〈0. 05）;（ 3） compared with control group,21 differences point were screened in VD model group,and the expression of 4 kind proteins was up-regulated,they respectively wereα-enolase,Thioredoxin like protein1,Dual specificity mitogen activated protein kinase kinase1 and Dihydropyrimidinase related protein2,which were identified by Mass Spectrum; 1 protein expression named Glutathione synthetase was down-regulated. Conclusion The VD rat model was successfully achieved with 2-VO; several proteins in the process of VD are discovered by proteomics research,which can provide pathogenesis basis of VD in theory,and supply therapy clues for VD.