【摘要】 背景:血管性痴呆患者存在额叶皮质及海马胆碱能神经元受损,可能是导致患者认知功能受损的形态学基础。目的:探讨神经干细胞与血管性痴呆大鼠海马胆碱能神经元变化的相关性。方法:纳入90只SD大鼠,随机均分为3组,其中假手术组仅分离颈总动脉,模型组和神经干细胞移植组采用两血管结扎法建立血管性痴呆动物模型,神经干细胞移植组在建立血管性痴呆动物模型之后向大鼠海马CA1区注射5μL神经干细胞,另外两组按照同样的操作注射相同剂量的生理盐水。移植后第3,7,14,30,60天,分别处死各组6只大鼠,采用S-P免疫组化法检测各组脑实质Brd U阳性细胞和Ch AT阳性细胞分布情况,利用Morris水迷宫系统检测大鼠学习记忆能力。结果与结论:Brd U阳性细胞主要分布在大脑皮质区以及海马区,尤其是血管周围。在基底核和丘脑以及室管膜区,可观察到少量Brd U阳性细胞存在。随着时间的推移,Brd U阳性细胞数目不断下降,到移植后60 d,仅存在少量Brd U阳性细胞存活。移植后不同时间模型组和神经干细胞移植组的Ch AT阳性细胞数均显著大于假手术组(P<0.05);模型组Ch AT阳性细胞数显著低于神经干细胞移植组(P<0.05)。模型组寻找平台时间显著长于假手术组,穿越平台次数显著少于假手术组(P<0.05);神经干细胞移植组的寻找平台时间显著短于模型组,穿越平台次数显著大于模型组(P<0.05)。结果表明神经干细胞可以在大鼠脑内存活并发生迁移,显著改善血管性痴呆大鼠学习记忆能力,相关机制可能与海马胆碱能神经元分化和生长有关。更多还原

【Abstract】 BACKGROUND: The damage of cholinergic neurons in the frontal cortex and hippocampus in patients with vascular dementia may be the morphological basis of the impairment of cognitive function. OBJECTIVE: To investigate the relationship between neural stem cell transplantation and the changes of cholinergic neurons in the hippocampus of rats with vascular dementia. METHODS: Ninety Sprague-Dawley rats were randomly divided into three groups, 30 rats in model group, 30 in neural stem cell transplantation group and 30 in sham operated group. Vascular dementia models were established by ligation of the common carotid artery in the model and neural stem cell transplantation groups. The common carotid artery was only separated but not ligated in the sham operated group. After modeling, the neural stem cell transplantation group was injected with 5 μL neural stem cells in the hippocampus CA1 area, while the other two groups were injected the same dose of normal saline. At 3, 7, 14, 30, 60 days after treatment, six rats of each group were sacrificed, respectively. Distributions of Brd U positive cells and Ch AT positive cells were detected by S-P immunohistochemical method. The learning and memory abilities of rats were detected by Morris water maze system. RESULTS AND CONCLUSION: Brd U positive cells were mainly distributed in the cortex and hippocampus, especially around the blood vessels, and there was the presence of focal aggregation. A small amount of Brd U positive cells were observed in the basal ganglia and thalamus as well as in the ependyma. Brd U positive cells were counted at different time after operation. The number of Brd U positive cells decreased with time, and only a small number of Brd U positive cells were observed at 60 days after transplantation. The number of Ch AT positive cells at different time after transplantation was ranked as follows: neural stem cell transplantation group > model group > sham operated group(P < 0.05). Compared with the model group, the time for searching the platform was significantly lower in the neural stem transplantation group and sham operated group, but the number of crossing the platform was significantly higher in the neural stem cell transplantation group and sham operated group(P < 0.05). The results show that neural stem cells could be transplanted into the rats with vascular dementia, and the cells could survive and migrate in the brain of rats and significantly improve the learning and memory ability. This mechanism may be related to the differentiation and growth of cholinergic neurons in the hippocampus.更多还原