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  

Effect of L-nitro arginine on neuronal nitric oxide synthase positive neurons distribution,nitric oxide synthase activity and nitric oxide content in hippocampus of Alzheimer's disease model mice

作　　者：李囡[1] 尹逊河[1] 邱建华[1] 李太祥[2] 王宪龙[1] 李猛猛[1] 

机构地区：[1]山东农业大学动物科技学院,山东泰安271018 [2]山东省泰安市科学技术情报研究所,山东泰安271000

出　　处：《中国兽医学报》2015年第6期961-966,共6页Chinese Journal of Veterinary Science

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)

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(P<0.01或P<0.05),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(P<0.05);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(P<0.05)。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。To study the content of NO and the activity of NOS in hippocampus of mice with Alzheimer disease induced by combined administration of D-galactose and aluminium,this paper compared and cured the AD mice models by using NOS inhibitor L-NNA and donepezil hydrochloride.Healthy KM mice 160,the relative body quality between(20±2)g as lab animals,were divided into the model group and control group of normal saline,the treatment group of Alzheimer disease mice with donepezil hydrochloride and L-NNA in random.The mode of Alzheimer disease mice were established by combining administration of D-galactose and aluminium,the content of NO and the activity of NOS of hippocampus were detected every week acrossing the whole process by biochemical technology.The results indicated that the content of NO increased slowly at the beginning,the highest at the fourth week,and then kept high content from 4to 12 weeks.In the two therapy group,the content of NO were extremely notable difference with model group(P<0.01 or P<0.05),and the group of L-NNA was lower than the group of donepezil hydrochloride between 4to 8weeks(P<0.05).The change of NOS and the content of NO in hippocampus are consistent.Using SABC immunohistochemical method to detected the neuronal NOS positive neurons.The density of hippocampus neuronal NOS positive neurons decreased,cell color became light,soma-sectional area and the longest tab became smaller,and were improved significantly after treatment(P<0.05).The results suggested that,the high concentrations of No play a neurtoxic role in damage to brain neurons in AD.Donepezil hydrochloride and L-NNA reduced the content of NO in hippocampus,by inhibiting NOS activity,leading a significant protective effect on neurons of hippocampus of Alzheimer disease rats.

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 

分 类 号：R749.16[医药卫生—神经病学与精神病学]