脑室内移植嗅成鞘细胞改善大鼠阿尔茨海默病的症状  

Transplantation of olfactory ensheathing cells to the intracerebral ventricle improves symptoms of AIzheimer＇s disease in rats

作　　者：姚柏春[1] 孙天敏[2] 李聪 王金勇[1,4] 李勇[1] 王配军[1] 李文春[1] 

机构地区：[1]郧阳医学院基础医学研究所,湖北十堰442000 [2]郧阳医学院图书馆 [3]不详 [4]郧阳医学院2006级护理本科

出　　处：《老年医学与保健》2009年第5期286-289,299,共5页Geriatrics & Health Care

摘　　要：目的探讨嗅成鞘细胞（olfactory ensheathing cells，OECs）脑室内注射对大鼠阿尔茨海默病的影响。方法sD大鼠双侧海马注射ABl．40，建立AD大鼠模型。实验动物分为四组：正常对照组、AD模型组、OECs移植组、MCSF注射组，每组10只。体外原代培养嗅成鞘细胞并将其移植至AD大鼠侧脑室。运用行为学测试、组织化学、原位杂交结合图像分析以及电镜等技术，观察、比较各组大鼠学习记忆能力、海马CA1区线粒体细胞色素氧化酶（cytochrome oxidase，COX）活性、细胞色素氧化酶Ⅱ型亚基（COⅡ）mRNA表达、一氧化氮合酶（nitric oxide synthase，NOS）阳性神经元数，以及CA1区神经元线粒体超微结构等指标的变化。结果与正常对照组比较，AD模型组大鼠空间学习记忆能力、海马CA1区线粒体COX活性及CO II mRNA表达、NOS阳性神经元数明显降低或减少俨〈0．05），线粒体数肇减少，结构不清、肿胀、空泡样变、嵴断裂；嗅成鞘细胞移植明显上调上述指标俨〈0．05），并对神经元线粒体超微结构有明显的保护作用。结论嗅成鞘细胞移植通过改善AD大鼠学习记忆能力、提高海马COX活性和CO1ImRNA、NOS阳性神经元表达以及保护神经元线粒体等作用，对大鼠阿尔茨海默病具有明显的治疗作用。Objective To probe the effects of intracerebral ventricle injection of olfactory ensheathing cells （OECs） for the treatment of Alzheimer＇s Disease （AD） in rats. Methods The AD animal model was established by injection of Aβ1-40 into the hippocampus CAl. Forty rats were equally divided into normal control group, AD model group, OECs transplant group and manpower cerebral spinal fluid （MCSF） injection group. OECs were cultured in vitro and injected to the intracerebral ventricle. The learning and memory abilities of the rats were verified by the performance of Morris water maze task, with the method of enzyme histochemical staining coupled with computer image analysis system. COX activity in the hippocampus CA1 was observed. CO 1/mRNA expression was observed by in situ hybridization. Ultrastructural changes of neural mitochondria in rat hippocampus CA1 were observed under a transmission electron microscope. The total number of nitric oxide synthase positive neurons of the hippocampus was observed by NADPH-d hist.ochemical staining. Results Compared with the control group, the learning and memory abilities of Aβ-injected rats were lower, the number and ultrastructure of neural mitochondria of the hippocampus changed markedly, and the activity of cytochrome oxidase and the expression of CO II mRNA in the hippocampus CA1 declined markedly. The total number of NOS positive neurons of OECs in the OECs transplant group was higher than that in the AD model and MCSF injection groups. However, OECs transplantation improved the above mentioned indexes in varying degrees. Conclusion The data demonstrated that the efficacy of OECs on AD may partly result from their abilities of improving spatial learning and memory, cytochrome oxidase activity, mRNA expression of CO 11 and NOS positive neurons, and the number and ultrastructure of neural mitochondria of the hipocampus.

关 键 词：阿尔茨海默病 电子传递复合物IV 一氧化氮合酶 线粒体 嗅神经 移植 

分 类 号：R745.7[医药卫生—神经病学与精神病学]