摘要
目的观察Kh D IC(KM hn/IDLJ IMP CAMS)小鼠海马神经细胞线粒体自由基水平的变化及APP17肽(-βamyloid precursor pro-tein,APP,319-335肽段)的影响。方法2.5月龄的Kh D IC小鼠随机分为模型组和APP17肽治疗组,正常对照组采用月龄和性别相匹配的正常昆明(KM)小鼠。APP17肽治疗组给予皮下注射APP17肽,每只每次0.34μg,每周3次;模型组和正常对照给予等量的生理盐水;25 w后成模。应用水迷宫试验观察小鼠学习、记忆功能的变化,应用羟胺法和硫代巴比妥酸(TBA)比色法分别检测了海马神经细胞线粒体抗氧化酶活性及自由基水平。结果①水迷宫结果显示,模型组小鼠存在明显的学习和记忆功能障碍,其游完全程的时间和错误反应次数均较正常对照组增多(P<0.05);APP17肽治疗组小鼠的行为学障碍明显轻于模型组,其上述的水迷宫检测结果与正常对照组比较无显著性差异。②与正常对照组比较,模型组小鼠海马神经细胞线粒体超氧化物歧化酶(SOD)活性明显降低(P<0.01),丙二醛(MDA)含量显著升高(P<0.01);APP17肽治疗组检测结果与正常对照组接近,SOD活性高于模型组(P<0.01),而MDA含量低于模型组(P<0.01)。结论①Kh D IC小鼠存在学习和记忆功能障碍;而且其海马神经细胞线粒体氧化应激反应明显加剧。②APP17肽具有清除自由基和抑制氧化应激反应的作用,从而提高脑组织的抗氧化能力,保护学习、记忆功能。
Objective To observe the changes of free radical level in mitochondria in hippocampal neurons of KM hn / IDLJ IMP CAMS （ Kh DIC） mice and the influence of β-Amyloid precursop protein,APP,319-335 （APP17-mer） peptide on the oxidative stress. Methods The 2.5-month-old Kh DIC mice were randomly divided into the model group and the APP17-mer peptide group; the normal Kunming （KM） mice with matched age and sex were adopted as control group. The APP17-mer peptide group was injected with APP17-mer peptide subcutaneously in a dose of 0.34 μg/per mouse, three times once week, while the model group and the control group were injected with same dose of saline. After 25 weeks,water maze test was used to evaluate the learning and memory of these mice. Then hydroxy lamine reaction and thiobarbituric acid （TBA） reaction were used to assay the activity of superoxide dismutase （SOD） and contents of malondialdehyde （MDA） in mitochondria in hippocampal neurons respectively. Results （ 1 ） The water maze test showed that the full-course swimming time and numbers of error in the model group were significantly increased as compared with those of control group （ P 〈 0.05 ）, the results of APP17-mer peptide group was the same as that in normal control. （2） The activity of SOD decreased（ P 〈 0.01 ）, and the contents of MDA significantly increased（ P 〈0.01 ）in the model group comparing to those in normal controls. The detective results in APP17-mer group were similar to those of normal controls,but activity of SOD was higher than that in model group （P 〈 0.01 ） ,the content of MDA was lower than that in model group （ P 〈 0.01 ）. Conclusions Kh DIC mice have learning and memory impairment,moreover obviously increased oxidative stress reaction in mitochondria in hippocampal neurons. APP17-mer peptide has the effect of eliminating free radicals and inhibiting oxidative stress,thereby promote the antioxidant ability and secure learning and memory function.
出处
《中国老年学杂志》
CAS
CSCD
北大核心
2005年第9期1097-1099,共3页
Chinese Journal of Gerontology
基金
北京市自然科学基金资助项目(项目编号70310037)
