慢性脑缺血导致血管重塑、血流动力学变化、神经元变性和认知功能损伤-神经病学专业毕业论文.docxVIP

万方数据 万方数据 中文摘要 目的：探究慢性脑缺血大鼠在缺血前后动态血流变化、血管新生、细胞形态学变化 以及认知功能改变。 方法：采用分步双侧颈总动脉结扎法制作慢性脑缺血模型。缺血前后分别用 3D ASL 技术测定双侧顶叶皮层、纹状体和小脑区域脑血流（CBF）值；MRA 显示大鼠脑大 动脉系统及测量椎动脉直径和面积；HE 染色观察小脑颗粒细胞在慢性脑缺血前后变 化情况；CD34、Iba1 和 GFAP 免疫荧光染色观察微血管、小胶质细胞和星形胶质细 胞变化情况；水迷宫评估大鼠慢性脑缺血前后认知功能改变。 结果：皮层、纹状体和小脑部位的 CBF 值在右侧颈总动脉结扎（RCCAO）后即出 现明显下降，一直维持到缺血后 2 wk，然而在缺血后 3 wk-6 wk 恢复至基态水平。 椎动脉在双侧颈总动脉结扎后开始扩张直到缺血后 6 wk。微血管数量在缺血后 2 wk-4 wk 呈下降状态，而 6 wk 呈上升状态。皮层、纹状体部位神经元变性发生在缺 血后的 2 wk-6 wk，但胶质细胞数量在缺血后 4 wk 见明显增加。缺血前后小脑颗粒 细胞层厚度无明显变化。水迷宫结果表明缺血时间越长，大鼠的认知功能越差。 结论：慢性脑缺血可引起代偿机制以维持正常脑血流灌注，然而这种代偿还不足以 阻止缺血引起的神经元变性和认知功能损伤。 关键词：双侧颈总动脉结扎；脑血流；椎动脉；血管新生；神经元变性 I Abstract Objective: The purpose of this study was to investigate dynamic changes in CBF, angiogenesis and cellular morphology, and also studied cognitive impairment of chronic cerebral hypoperfusion (CCH) rats. Methods: Two step bilateral common carotid artery occlusion (BCCAO) method was used to induce CCH model. We used 3D ASL technique to measure cerebral blood flow (CBF) in bilateral cortex, striatum and cerebellum before and after BCCAO; MRA showed the cerebral vasculature and measured the diameter and area of vertebral arteries; HE staining was used to observed the change of granular layer in cerebellum before and after BCCAO; CD34、Iba1 and GFAP immunofluorescent staining to observe the change of micro-vessels, microglial cells and astrocytes; Morris water maze to evaluate the cognitive damage induced by CCH. Results: The CBF of the cortex, striatum and cerebellum dramatically decreased after right common carotid artery occlusion (RCCAO), and remained lower level at 2 wk after BCCAO. It returned to the sham level from 3 to 6 wk. Dilation of vertebral arteries occurred immediately after BCCAO and sustained to 6 wk after BCCAO. The number of micro- vessels declined at 2, 3 and 4 wk but increased at 6 wk after BCCAO. Neuronal degeneration occurred in the cortex and striatum from 2 to 6 wk, but the number of glial cells dramatically increased at 4 after BCCAO. Morr