L-硝基精氨酸对阿尔茨海默症小鼠脑海马nNOS阳性神经元分布、NOS活性及NO含量变化的影响

发布时间：2018-02-23 03:08

本文关键词： 盐酸多奈哌齐 L-硝基精氨酸脑海马阿尔茨海默症一氧化氮合酶　出处：《中国兽医学报》2015年06期 　论文类型：期刊论文

【摘要】：为了研究D-半乳糖联合铝诱导的小鼠阿尔茨海默症(AD)脑海马一氧化氮合酶(NOS)活性和一氧化氮(NO)含量的变化及L-NNA和盐酸多奈哌齐对其变化的影响,探讨NO在阿尔茨海默症中的作用机制及2种药物对脑神经元的保护作用。选取2月龄健康昆明小鼠160只,体质量(20±2)g,随机分为正常对照组、模型组、盐酸多奈哌齐治疗组及L-NNA治疗组,利用D-半乳糖联合三氯化铝建立小鼠AD模型,应用生化检测技术测定各组脑海马在造模后每周NOS活性及NO含量。结果表明,模型组海马内NOS活性开始呈缓慢升高,从第4周开始呈显著升高,保持较高含量至12w造模结束;两治疗组脑海马NOS活性在各时间点极显著或显著低于模型组(P0.01或P0.05),并且L-NNA在4~8周时降低脑海马NOS活性的程度好于盐酸多奈哌齐治疗组(P0.05);NO含量的变化随着NOS活性的变化而变化;利用SABC免疫组织化学方法检测各组脑海马神经型NOS(nNOS)阳性神经元,发现模型组脑海马nNOS阳性神经元密度降低,细胞着色变淡,胞体截面积和最长突起长度变小,经过治疗后神经元密度增加,胞体截面积和最长突起长度显著改善(P0.05)。结果提示NO参与了AD形成过程,高浓度的NO能发挥神经毒性作用损害脑组织;L-NNA通过抑制NOS的活性,降低了脑海马NO的含量,对阿尔茨海默症中海马神经元具有明显的保护作用。
[Abstract]:In order to study the changes of nitric oxide synthase (NOS) activity and nitric oxide (no) content in hippocampus of mice with Alzheimer's disease induced by D-galactose and aluminum, the effects of L-NNA and Donepezil hydrochloride on the activity of nitric oxide synthase (NOS) and the effect of Donepezil hydrochloride on the activity of nitric oxide synthase (NOS) were studied. To explore the mechanism of no in Alzheimer's disease and the protective effect of two drugs on brain neurons, 160 healthy Kunming mice of 2 months old, 20 卤2g body weight, were randomly divided into normal control group and model group. The AD model of mice was established by Dgalactose combined with aluminum trichloride in Donepezil hydrochloride treatment group and L-NNA treatment group. The activity of NOS and the content of no in each group were measured by biochemical detection technique. In the model group, the activity of NOS in hippocampus began to increase slowly, increased significantly from the 4th week, and maintained a high content until the end of modeling at 12 weeks. The activity of NOS in the two groups was significantly lower than that in the model group at each time point (P0.01 or P0.05A), and L-NNA decreased the activity of NOS in the hippocampus at 48 weeks after treatment, which was better than that in the Donepezil treated group with the change of no content with the change of NOS activity. The SABC immunohistochemical method was used to detect the NOSnNOS- positive neurons of the hippocampal nerve type in each group. It was found that the density of nNOS positive neurons in the model group was decreased, the cell staining was decreased, the cell body cross-sectional area and the length of the longest protrusions were reduced. After treatment, the neuronal density increased, the cell body cross-sectional area and the length of the longest process improved significantly (P 0.05). The results suggested that no was involved in the formation of AD, and high concentration of no could play a neurotoxic role in damaging the activity of NOS in brain tissue by inhibiting the activity of L-NNA. It has obvious protective effect on hippocampal neurons in Alzheimer's disease by decreasing the content of no in hippocampus.
【作者单位】：山东农业大学动物科技学院;山东省泰安市科学技术情报研究所;
【基金】：国家自然科学基金资助项目(30671498) 山东省自然科学基金资助项目(Y2003D04)
【分类号】：R749.16

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