阿尔茨海默病大鼠模型脑内神经元型一氧化氮合酶神经元的变化(英文)

Alterations of the cerebral neurons containing neuronal nitric oxide synthase in rat models of Alzheimer's disease

目的观察阿尔茨海默病(AD)大鼠模型脑内神经元型一氧化氮合酶(nNOS)神经元的变化,探讨nNOS神经元与AD病理过程的关系。方法选用健康雄性Wistar大鼠32只,10～12周龄,采用海人酸损伤基底前脑胆碱能神经元的方法,建立AD大鼠模型,用避暗法和穿梭箱法测试大鼠的学习记忆能力,免疫组化法检测脑内nNOS神经元的变化。结果大鼠模型基底前脑部ChAT神经元数目减少,实验组较对照组显著减少达40%(26±3vs43±3,t=2.483,P<0.01),大脑皮质中nNOS神经元形态发生改变,细胞突起显著减少,扭曲变形,断裂,突起上的分支减少,消失,树突缩短,胞体皱缩,胞质浓缩,酶染色深,表现出一系列变性的改变,且神经元数目减少(21±3vs31±4,t=1.906,P<0.05),海马中nNOS神经元形态及数目变化无显著性(18±3vs20±4,t=1.473,P>0.05)。结论nNOS神经元对神经元变性有易感性,nNOS神经元变性参与了AD病理过程的发生发展。

Aim To observe the changes of the cerebral neurons containing neuronal nitric oxide synthase (nNOS neurons) in rat models of Alzheimer's disease (AD) and to investigate the relationship between nNOS neurons and the pathological process of AD.Methods Sixteen healthy male Wistar rats were subjected to kainic acid injection into the bilateral nucleus basalis magnocellularis to induce injuries of the cholinergic neurons for the establishment of AD models,with another 16 rats receiving normal saline injection to serve as the control group.The learning and memory ability of the rats was evaluated by dark avoidance test and shuttle box test, and immuno cytochemical assay was performed to identify the alterations of cholineacetyltransferase (ChAT) and nNOS neurons in the brain.Results The number of ChAT positive neurons in the basal forebrain underwent a decrease by 40% in the rat models,compared with the control rats (26± 3 vs 43± 3, t=2.483, P< 0.01).The morphological alterations occurred in nNOS neurons in the cerebral cortex of the AD models, featured by reduced quantity of neuritis and their branches,with shortened dendrites that appeared distorted or fragmented.The neurons were shrunk,the cytoplasm condensed and contained dark staining substances,showing also degenerative changes.Significant reduction of nNOS neurons occurred in the cerebral cortex of rat AD models in comparison with the control group (21± 3 vs 31± 4,t=1.906,P< 0.05 ),but the nNOS neurons in the hippocampus and the dentate gyrus were not significantly afftected in terms of the morphology and numbers (18± 3 vs 20± 4,t=1.473,P >0.05).Conclusion nNOS neurons in rat cerebral cortex were vulnerable to neuron degeneration, which probably participate in the pathological progress of AD.