急性酒精中毒对老龄大鼠纹状体NO和nNOS及学习记忆的影响

Effect of Learning and Memory and NO and nNOS Levels of Corpus Striatum Brain Tissues in Aged Rats with Acute Alcoholism

目的通过观察急性酒精中毒对老龄大鼠学习记忆的影响并测定脑纹状体组织中一氧化氮(NO)与神经型一氧化氮合酶(nNOS)含量的变化,探讨酒精中毒影响学习记忆的分子机制。方法老龄(Sprague-Dawley,S-D)大鼠购回后适应性饲养两天,随机分为2组,酒精组腹腔一次性注射乙醇2.5g/kg[用生理盐水配成含20%乙醇(w/v)溶液]制备急性酒精中毒大鼠模型;对照组注射等容量的生理盐水。Y-型迷宫检测大鼠学习记忆成绩、硝酸还原酶法检测鼠脑纹状体中NO的含量、免疫组化方法检测鼠脑纹状体中nNOS的含量。结果(1)酒精组大鼠达到学会标准所需要的训练次数(36.46±12.23)明显大于对照组(28.49±9.32),P<0.05;(2)纹状体NO的含量在酒精组为22.31±8.78,对照组为9.67±4.77,前者明显高于后者(P<0.01);(3)纹状体nNOS阳性神经元的数量在酒精组为10.40±4.47,对照组为5.30±3.25,前者明显高于后者(P<0.05)。结论上述结果提示酒精的神经毒性作用可能与脑纹状体组织中nNOS和NO信号通路有关。

Objective In order to investigate the molecular mechanism of alcoholism acting on learning and memory, the dysfunction of learning and memory cognitive function was observed by using the Y maze test and the content of nitric oxide（NO） and neuronal nitric oxide synthase（nNOS） was determined in aged rats with acute alcoholism. Methotis The aged male Sprague -Dawley rats were fed with normal diet for 2 days at our laboratory. Animals were randomly divided into two groups. The ethanol group animals were intraperitoneally administered with ethanol once in a dose of 2.5 g/kg （20% （w/v） ethanol solution was mixed by saline ）, but the control group animals were injected with saline in the same way. The tests of learning and memory were performed at Y - maze after 6 hours in a laboratory with a dark and quiet around. The time that rats reach the safe area is recorded. The qualified standard of maze test was that the rats arrive in safe area needs 9 times during 10 experiments. Then brains were removed and the content of NO and nNOS expression in corpus striatum were determined by the method of nitrate reductase and immunohistochemistry, respectively. Results （ 1 ） the training times to reach qualifying standards of Y - maze in ethanol group was 36.46 ± 12.23, but that in control group was 28.49 ± 9.32, namely, and the training times of the former was more than those of the latter（ P 〈 0.05 ） ; （ 2 ） The content of NO of ethanol group （ 22.31 ± 8.78 ） in corpus striatum were also higher than that of control group （9.67 ± 4.77） （ P 〈 0.01 ）. （3） the levels of nNOS positive neurons of ethanol group （ 10.40 ± 4. 47）in corpus striatum were also higher than those of control group（5.30 ±3.25） （P 〈0.05）. Conclusions These findings suggest that acute alcoholic intoxication may impair learning and memory and the mechanism of ethanol neuro- toxicity would be partly involved in the signal pathway of NOS and NO in corpus striatum of the brain.