阿尔茨海默病转基因小鼠早期记忆功能障碍与氧化应激损伤关系的实验研究

目的 观察转APP/PS1基因阿尔茨海默病(AD)小鼠(APP/PS1小鼠)早期空间学习记忆功能及相关氧化应激反应指标的变化,并探讨它们之间的相关性.方法 应用Morris水迷宫评定APP/PS1小鼠及相应野生型(WT)小鼠的空间学习记忆功能,采用ELISA方法检测脑组织中超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-PX)活性以及丙二醛(MDA)和蛋白质羰基的含量,并进行相关性分析.结果 2组小鼠的空间学习能力无明显差异(P＞0.05),而APP/PS1小鼠在目标象限(定位航行实验中平台所置第二象限)中航行时间占总时间的百分比(29.02±4.27)%较WT小鼠(47.39±6.01)%显著下降(t=0.000,P＜0.05),APP/PS1小鼠在目标象限中航行路程占总路程的百分比(28.85±3.77)%较WT小鼠(46.70±5.60)%也显著下降(t=0.000,P＜0.05),提示APP/PS1小鼠的空间记忆功能较WT小鼠显著下降.2组小鼠脑组织中的MDA含量、SOD和GSH-PX活性均无明显差异(P均＞0.05),而APP/PS1小鼠脑组织中的蛋白质羰基含量(2.67±0.19)较WT小鼠(2.38±0.15)显著增加(t=0.0088,P＜0.05).相关性分析表明:APP/PS1小鼠蛋白质羰基含量与目标象限航行时间百分比呈显著负性相关(r=-0.639,P＜0.05),APP/PS1小鼠蛋白质羰基含量与目标象限航行路程百分比呈显著负性相关(r=-0.636,P＜0.05).结论 APP/PS1小鼠早期空间记忆功能损害与脑组织中的蛋白质羰基含量升高呈负性相关,提示氧化应激导致的蛋白质羰基化在AD早期记忆损害发病过程中具有重要作用.

Abstract：

Objective To investigate the spatial learning and memory ability,the changes of indicators of oxidative stress,and their relationship in transgenic APP/PS1 mouse model of Alzheimer's disease(APP/PS1 mice). Methods The spatial learning and memory ability were assessed by Morris water maze test,and the activity or content of SOD, GSH-PX, MDA, and protein carbonyl in brain tissues were measured by ELISA in the APP/PS1 and wild type (WT) mice. Furthermore, the relationship between the learning and memory performances and the indicators of oxidative stress was examined. Results No significant difference in the spatial learning was observed between the APP/PS1 and WT mice (P ＜0. 05). The spatial memory which was measured as the percentage of time traveling in the targeted quadrant to the total traveling time was significantlydeclined in the APP/PS1 mice(29. 02 ± 4. 27) % as compared with the WT mice(47. 39 ± 6. 01) %(t =0. 000 ,P ＜0. 05). The percentage of length of traveling in the targeted quadrant to the total length traveled was significantly lower in the APP/PS1 mice(28. 85 ±3.77)% compared with the WT mice(46. 70 ±5.60)% (t =0. 000,P ＜0. 05). These findings indicated that the spatial learning and memory ability of APP/PS1 mice was significantly decreased compared to WT mice. There was no significant difference in activity or content of SOD,GSH-PX,and MDA in brain tissues between the APP/PS1 and WT mice (P ＜ 0. 05), while the content of protein carbonyl was significantly elevated in the APP/PS1 mice (2. 67 ±0. 19) than in the WT mice (2. 38 ±0. 15)(t = 0. 008, P ＜ 0. 05). Correlation analysis revealed that the elevated protein carbonyl was negatively correlated with the percentage of length traveled in the targeted quadrant(r = - 0. 639, P ＜ 0. 05) and the percentage of time traveled in the targeted quadrant(r = - 0. 636 ,P ＜ 0. 05). Conclusion The spatial memory impairment was negatively correlated with the elevated protein carbonyl in the APP/PS1 mice, suggesting that protein carbonylation caused by oxidative stress might play an important role in the development of memory impairment in the early stage of Alzheimer's disease.

Relationship between early memory impairment and oxidative stress in transgenic mouse model of Alzheimer's disease

Objective To investigate the spatial learning and memory ability,the changes of indicators of oxidative stress,and their relationship in transgenic APP/PS1 mouse model of Alzheimer's disease(APP/PS1 mice). Methods The spatial learning and memory ability were assessed by Morris water maze test,and the activity or content of SOD, GSH-PX, MDA, and protein carbonyl in brain tissues were measured by ELISA in the APP/PS1 and wild type (WT) mice. Furthermore, the relationship between the learning and memory performances and the indicators of oxidative stress was examined. Results No significant difference in the spatial learning was observed between the APP/PS1 and WT mice (P ＜0. 05). The spatial memory which was measured as the percentage of time traveling in the targeted quadrant to the total traveling time was significantlydeclined in the APP/PS1 mice(29. 02 ± 4. 27) % as compared with the WT mice(47. 39 ± 6. 01) %(t =0. 000 ,P ＜0. 05). The percentage of length of traveling in the targeted quadrant to the total length traveled was significantly lower in the APP/PS1 mice(28. 85 ±3.77)% compared with the WT mice(46. 70 ±5.60)% (t =0. 000,P ＜0. 05). These findings indicated that the spatial learning and memory ability of APP/PS1 mice was significantly decreased compared to WT mice. There was no significant difference in activity or content of SOD,GSH-PX,and MDA in brain tissues between the APP/PS1 and WT mice (P ＜ 0. 05), while the content of protein carbonyl was significantly elevated in the APP/PS1 mice (2. 67 ±0. 19) than in the WT mice (2. 38 ±0. 15)(t = 0. 008, P ＜ 0. 05). Correlation analysis revealed that the elevated protein carbonyl was negatively correlated with the percentage of length traveled in the targeted quadrant(r = - 0. 639, P ＜ 0. 05) and the percentage of time traveled in the targeted quadrant(r = - 0. 636 ,P ＜ 0. 05). Conclusion The spatial memory impairment was negatively correlated with the elevated protein carbonyl in the APP/PS1 mice, suggesting that protein carbonylation caused by oxidative stress might play an important role in the development of memory impairment in the early stage of Alzheimer's disease.