阿司匹林对阿尔茨海默病模型大鼠学习记忆能力的保护作用及其对炎症因子IL-6、IL-1β和TNFα表达的影响

Effect of aspirin on learning and memory abilities and brain expression of IL-6, IL-1βand TNFαin Alzheimer’s model rats

目的：探讨阿司匹林对阿尔茨海默病（AD）是否具有防治作用，及是否对相关炎性因子表达存在影响。方法本研究在体内条件下用侧脑室定向注射β淀粉样蛋白（Aβ）25-35模拟AD的基本病理改变，用阿司匹林进行干预，测试大鼠在Morris水迷宫中的逃避潜伏期，并用ELISA检测大鼠脑组织内炎症因子白细胞介素（IL）-6、IL-1β和肿瘤坏死因子α（TNFα）的表达情况。将50只大鼠随机分为5组，每组10只。（1）高剂量阿司匹林干预组：大鼠给予含阿司匹林2g/L的蒸馏水溶液喂服，自由进食。3周后侧脑室内注射Aβ溶液5μl，再予含阿司匹林2g/L的蒸馏水溶液喂服3周，自由进食。（2）中剂量阿司匹林干预组：给予含阿司匹林1g/L的蒸馏水溶液喂服，其余同前。（3）低剂量阿司匹林干预组：给予含阿司匹林0.5g/L的蒸馏水溶液喂服，其余同前。（4）模型组：给予蒸馏水喂服，其余同前。（5）假手术组：给予蒸馏水喂服，3周后侧脑室内注射无菌生理盐水5μl，再予蒸馏水喂服，自由进食。第6周结束时，使用Morris水迷宫测试大鼠学习记忆能力改变。然后处死大鼠使用ELISA方法检测大鼠脑组织内IL-6，IL-1β和TNFα水平。结果（1）阿司匹林各剂量干预组逃避潜伏期较模型组缩短，差异具有统计学意义。（2）IL-1β水平以模型组最高，假手术组最低，各不同阿司匹林剂量干预组水平在前两组之间；而3组阿司匹林干预组中，分别为低剂量组最高，高剂量组最低；差异具有统计学意义。（3）IL-6水平以模型组最高，假手术组最低，阿司匹林各剂量干预组介于两者之间，但总体间差异无统计学意义。（4）TNFα水平以模型组最高，假手术组最低，各不同阿司匹林剂量干预组介于两者之间；各剂量组之间又分别以中剂量组最高，高剂量组最低；差异有统计学意义。结论侧脑室定向注射Aβ25-35能使大鼠学习记忆能力下降。阿司匹林干预可改善AD模型大鼠的学习记忆能力。阿司匹林可能下调IL-1β，IL-6和TNFα等炎症因子的释放，从而对AD模型大鼠学习记忆能力起到保护作用。

Objective To investigate whether there is preventive and treatment effect of aspirin on the rat model of Alzheimer’s disease （AD） and its influence on the expression of interleukin （IL）-6, IL-1βand tumor necrosis factorα（TNFα） in the models. Methods A total of 50 SD rats were randomly divided into 5 groups： control group, model group, and low-, middle-and high-dosed aspirin groups. After fed with normal saline containing aspirin at 0, 0.5, 1 and 2g/L respectively for the later 4 groups for 3 weeks, the rats model of AD was established by injecting 5 μl amyloid-beta protein 25-35 （Aβ25-35） into the lateral cerebral ventricle followed by another 3 weeks’ aspirin treatment, while those of control was given normal saline at same volume. The escape latency of the rats was tested in Morris water maze, and the levels of IL-6, IL-1β, TNFαin the brain were detected by enzyme linked immunosorbent assay （ELISA）. Results The mean escape latency was significantly shorter in the high-, middle- and low-dosed aspirin groups than in the control group. The brain levels of IL-1β was the highest in the＆nbsp;model group, the lowest in the control group, and in a decreasing order in the low-, middle- and high-dosed aspirin groups, with significant difference among them. The brain level of IL-6 was in a similar trend as that of IL-1βin the 5 groups, but there was no significant difference among them. The level of TNFα was also the highest in the model group, and the lowest in the control group, and those in the other 3 groups were between the 2 values. Among the 3 aspirin groups, the middle-dosed group had the highest level of TNFα, and the low-dose group had the lowest level, with significant difference between the 2 groups. Conclusion Lateral cerebral ventricle injection of Aβ25-35 causes short-term decrease in learning and memory abilities in rats. Aspirin intervention attenuates the induced decrease in the abilities. It might exert the protective effect on the learning and memory abilities through down-regulating IL-1β, IL-6, and TNFαin the brain.