维生素E对阿尔茨海默病模型学习记忆能力损伤的改善作用

目的：观察维生素E对阿尔茨海默病（AD）模型小鼠学习记忆能力的改善作用及其机制。方法：采用D-gal与NaNO2联合腹腔注射方法建立AD模型小鼠，在造模同时及模型建立后两个时间点灌胃给予维生素E（28，280IU／kg）观察疗效，实验结束后水迷宫检测各组小鼠的逃避潜伏期的变化，化学比色法检测脑组织AChE、SOD活性、MDA含量；免疫组织化学方法检测大脑皮层Aβ、NF-B表达的变化。结果：造模同时给予维生素E可使D-gal与NaNO2联合诱导的AD模型鼠的逃避潜伏期缩短[第1天F（3，56）=6．959；第2天F（3，56）=6．689；第3天F（3，56）=17．379；第4天F（3，56）：13．391；P〈0．05]，AChE活性降低[F（3，28）=29．431，P〈0．05]，SOD活性提高[F（3，28）=7．372，P〈0．05]，MDA含量降低[F（3，28）=11．235，P〈0．05]；同时可明显降低AD模型鼠脑组织中Aβ、NF-κB的表达（P〈0．05）。模型建立后给予维生素E未发现上述变化。结论：维生素E可预防化学诱导的AD模型小鼠学习记忆能力损伤，可能机制与提高SOD活性、降低MDA含量、降低AChE活性、降低脑组织中Aβ、NF-κB的表达等相关。

Vitamin E administration improves learning and memory deficits in modeling Alzheimer's disease

AIM: To investigate the protective effects of Vitamin E on learning and memory in a mouse model of Alzheimer's disease (AD) and the mechanisms. METHODS: Mice were intragastric administrated with D-galactose (D-gal) and sodium nitrite ( NaNO_2) or vehicle, and divided into two main groups which received Vitamin E (28 and 280 IU/kg) at two different time points: either at the same time of admin-istration, or 2 h after D-gal and NaNO_2 dosing. After that,animals were trained and tested learning and memory abilities using the SMG-2 water maze. The changes of AChE and nuclear factor (NF)-κB were de-tected to explore the mechanism of Vitamin E's protective effects on learning and memory deficits. RESULTS: Mice administrated with Vitamin E at the same time of D-gal and NaNO_2 dosing showed a significant decrease in escape latency [ F (3,56) = 6.959 on day 1; F(3,56) = 6.689 on day 2; F(3,56) = 17.379 on day 3; F(3,56) = 13.391 on day 4; P < 0.05], accompanied with significant reduction of MDA [F(3,28)=11.235, P<0.05] and AChE activity [F(3,28)=29.431, P<0.05], increase of SOD activity [F(3,28) =7.372, P<0.05]. Vitamin E also decreased Aβ and NF-κB expressions in the cerebral cortex of AD mice model (P<0.05). However, mice receiving Vitamin E 2 h after D-gal and NaNO_2 dosing can not reverse the learning and memory deficits. CONCLUSION: Preventive administration of Vitamin E could remarkably prevent the learning and memory impairment, the machnism may be to increase the activity of SOD, reduce the activity of ACHE, the levels of MDA and the expressions of Aβ and NF-κB in the brain.