淫羊藿苷对线粒体损伤模型大鼠脑内β-淀粉样蛋白和神经营养因子的影响  

Effects of icariin on β-amyloid and neurotrophic factors in brain of mitochondrial deficiency model rats

作　　者：张如意[1] 张丽[1] 艾厚喜[1] 张兰[1] 李林[1] 

机构地区：[1]首都医科大学宣武医院药物研究室,教育部神经变性病学重点实验室,北京100053

出　　处：《中国中药杂志》2013年第9期1285-1289,共5页China Journal of Chinese Materia Medica

基　　金：国家重点基础研究发展计划(973)项目(2013CB531005);国家自然科学基金项目(30973513,81273498);首都卫生发展科研专项(2011-1001-04)

摘　　要：该研究主要是观察中药淫羊藿苷(ICA)对线粒体损伤模型大鼠脑内β-淀粉样蛋白(Aβ)含量和神经营养因子表达的影响。SD大鼠随机分为假手术组、模型组、ICA低、高剂量组(12,36 mg.kg-1)。各组大鼠皮下埋植Alzet微泵,假手术组给予生理盐水,其余各组给予线粒体呼吸链复合体IV抑制剂叠氮钠(0.5 mg.kg-1.h-1),共28 d,建立大鼠线粒体损伤模型。生化法测定大鼠海马线粒体复合体IV(即细胞色素C氧化酶)活性;ELISA法测定大鼠脑内Aβ含量;Western blot法和免疫组织化学法测定大鼠脑内神经营养因子及其受体的表达。结果显示叠氮钠微泵灌注可引起模型大鼠脑内线粒体细胞色素C氧化酶(COX)活性明显下降,Aβ含量升高,神经生长因子(NGF)、脑源性神经营养因子(BDNF)及其受体TrkB的表达减少。ICA灌胃给药明显改善模型大鼠的上述异常。结果表明ICA能够增强叠氮钠模型大鼠脑内线粒体活性,抑制Aβ产生,增强神经营养因子表达,提示ICA具有良好的治疗阿尔茨海默病的应用前景。The purpose of the present study was to investigate the effects of icariin （ICA） on the content of β-amyloid （Aβ） and the expression of neurotrophic factors in the brain of mitochondrial deficiency model rats. SD rats were infused subcutaneously with sodium azide, which is an inhibitor of mitochondrial respiratory chain complex IV, via a minipump （0. 5 mg · kg^-1· h^-1 ） for 28 days to establish the mitochondrial deficiency animal model. The activity of mitochondrial respiratory chain complex IV （ i. e. cytochrome C oxidase, COX） in hippocampus was measured by biochemical methods. ELISA method was used to detect the content of Aβ in the brain. The expression of neurotrophic factors was detected by Western blot and immunohistochemistry methods. Image analysis was per- formed by Image-pro software. The results showed that chronic infusion of sodium azide by minipump induced a significant decrease in the activity of mitochondrial cytochrome C oxidase, an obvious increase in the content of Aβ, and a marked decline in the expression of nerve growth factor （NGF）, brain-derived neurotrophic factor （BDNF） and its receptor TrkB in the brain of rats. Intragastrical admin- istration of ICA （12 or 36 mg · kg-1） significantly ameliorated all these abnormalities in the model rats. In conclusion, ICA can in- crease mitochondrial activity, inhibit Aβ production, and enhance the expression of neurotrophic factors in the brain of model rats in- duced by sodium azide. The resuhs suggested that ICA may have beneficial prospect for the treatment of Alzheimer＇s disease.

关 键 词：淫羊藿苷 阿尔茨海默病 线粒体 叠氮钠 Β-淀粉样蛋白 神经营养因子 大鼠 

分 类 号：R285.5[医药卫生—中药学]