嗅成鞘细胞移植对AD大鼠脑内COX活性和线粒体超微结构的影响_临床医学论文.docVIP

嗅成鞘细胞移植对AD大鼠脑内COX活性和线粒体超微结构的影响_临床医学论文 嗅成鞘细胞移植对AD大鼠脑内COX活性和线粒体超微结构的影响_临床医学论文 作者：姚柏春 孙天敏 王金勇 李勇 王配军 李文春 【摘要】 目的 探讨嗅成鞘细胞(OECs)移植对阿尔茨海默病(AD)大鼠脑内COX活性和线粒体超微结构的影响。方法 SD大鼠双侧海马注射Aβ1～40，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、人工脑脊液(MCSF)注射组，每组12只。体外原代培养OECs并将其移植至AD大鼠双侧海马。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和工具，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（COX）活性、细胞色素氧化酶Ⅱ型亚基(COⅡ)mRNA表达，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COⅡmRNA表达明显降低(0.05)，线粒体数量减少，结构不清、肿胀、空泡样变、嵴断裂；OECs移植明显上调上述指标(0.05)，并对线粒体超微结构有明显的保护作用。结论 OECs移植通过改善AD大鼠学习记忆能力、提高海马COX活性和COⅡmRNA表达以及保护线粒体等作用，对大鼠AD具有明显的治疗效果。 【关键词】 阿尔茨海默病；细胞色素氧化酶；线粒体；嗅成鞘细胞；移植 【Abstract】Objective To observe the effect of olfactory ensheathing cells (OECs) transplantation on cytochrome oxidase (COX) and the ultrastructure of hippocampal neurons mitochondrion in A1zheimer′s disease (AD) rats. Methods AD model was established by Aβ1～40 injected into hippocampus CA1. The rats were randomly divided into normal control, model, OECs transplantation and the manpower cerebral spinal fluid (MCSF) injected groups. There were 12 rats each group. OECs were cultured in vitro and injected into AD rat′s hippocampus. The ability of learning and memory was verified by the performance of Morris water maze task. The activity of COX in rat′s hippocampus CA1 was detected with the method of enzyme histochemical staining coupled with computer image analysis system. The expression of COⅡmRNA was observed by in situ hybridizajtion. Ultrastructural changes of neuron mitochondrion in rat′s hippocampus CA1 were viewed under transmisson electron microscope. Results Compared with the normal control group, the learning and memory ability of Aβinjected rats were lower, the number and ultrastructure of hippocampus neuron mitochrondrion had distinct change, the activity of COX and the expression of COⅡmRNA in hippocampus CA1 of the animals model of AD had been markly declined. OECs transplantation could improve above indexes. Conclusions The efficacy of OECs on AD maybe