中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2018, Vol. 13 ›› Issue (9): 1568-1574.doi: 10.4103/1673-5374.237120

• 原著:脑损伤修复保护与再生 • 上一篇    下一篇

氨基羟基乙酸可提高慢性酒精中毒大鼠的学习记忆能力

  

  • 收稿日期:2018-06-05 出版日期:2018-09-15 发布日期:2018-09-15
  • 基金资助:

    国家自然科学基金（YMX）（81530037, 81471158），河南省教育厅（ALD）项目（15A310006）

Aminooxyacetic acid improves learning and memory in a rat model of chronic alcoholism

Ai-Lin Du1, 2, Hao-Zhi Qin2, Hong-Bo Jiang1, 3, Peng-Yan Fu2, Ke Lou2, Yu-Ming Xu1   

  1. 1 Department of Neurology, First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China
    2 Department of Physiology and Neurobiology, Xinxiang Medical University, Henan Provincial Key Laboratory of Brain Research, Second Affiliated Hospital of Xinxiang Medical University, Xinxiang, Henan Province, China
    3 Third Affiliated Hospital of Xinxiang Medical University, Xinxiang, Henan Province, China
  • Received:2018-06-05 Online:2018-09-15 Published:2018-09-15
  • Contact: Yu-Ming Xu, M.D.,qin199793@126.com
  • Supported by:

    This study was supported by the National Natural Science Foundation of China (to YMX), No. 81530037, 81471158; a grant from the Department of Education of Henan Province of China (to ALD), No. 15A310006.

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摘要：

慢性酒精中毒严重损害中枢神经系统，导致学习记忆功能障碍，其机制与细胞损伤及硫化氢升高和钙离子超载密切相关。有研究显示，氨基氧乙酸是一种胱硫醚-β-合酶活性抑制剂，可减少脑组织硫化氢的形成。为此，实验设计观察氨基氧乙酸对大鼠学习记忆能力的影响。将大鼠随机分为3组，对照组正常喂养纯净水，酒精中毒组喂以含有6％酒精水28 d建立酒精中毒大鼠模型，氨基氧乙酸组先喂以含有6％酒精水14 d，第15-28天每天腹腔注射氨基羟基乙酸(5 mg/kg)溶液，各组共喂养28 d。以Morris水迷宫测试来测试大鼠的学习和记忆能力，以电镜观察海马线粒体超微结构，以分光光度法间接测定测定海马硫化氢水平，以超微量总ATP酶测定试剂盒测定ATP酶活性，以免疫组织化学和免疫印迹法测定髓鞘碱性蛋白表达。观察可见，与对照组相比，酒精中毒组大鼠第2，3，4天水迷宫实验中定位巡航实验潜伏期及游泳距离均延长，第5天空间探索实验跨越平台次数减少，在海马区出现线粒体嵴断裂、肿胀和变形，硫化氢水平升高，线粒体ATP酶活性降低，髓鞘碱性蛋白表达下调；而模型大鼠经氨基氧乙酸干预后上述全部结果指标均与上述呈反向变化。数据说明，氨基羟基乙酸可提高慢性酒精中毒大鼠的学习记忆能力，与用氨基氧乙酸干预降低了模型大鼠海马硫化氢水平及线粒体ATP酶酶活性，上调海马髓鞘碱性蛋白表达有关。

orcid:0000-0002-6268-0270(Yu-Ming Xu)

关键词: 氨基氧乙酸, 慢性酒精中毒大鼠, 硫化氢, Ca2+超载, 脑损伤, 学习记忆能力, Morris水迷宫, 髓鞘碱性蛋白, 线粒体, ATP酶活性, 神经再生

Abstract:

Chronic alcoholism seriously damages the central nervous system and leads to impaired learning and memory. Cell damage in chronic alcoholism is strongly associated with elevated levels of hydrogen sulfide (H2S) and calcium ion overload. Aminooxyacetic acid is a cystathionine-β-synthase activity inhibitor that can reduce H2S formation in the brain. This study sought to observe the effect of aminooxyacetic acid on learning and memory in a chronic alcoholism rat model. Rats were randomly divided into three groups. Rats in the control group were given pure water for 28 days. Rats in the model group were given 6% alcohol for 28 days to establish an alcoholism rat model. Rats in the aminooxyacetic acid remedy group were also given 6% alcohol for 28 days and were also intraperitoneally injected daily with aminooxyacetic acid (5 mg/kg) from day 15 to day 28. Learning and memory was tested using the Morris water maze test. The ultrastructure of mitochondria in the hippocampus was observed by electron microscopy. H2S levels in the hippocampus were measured indirectly by spectrophotometry, and ATPase activity was measured using a commercial kit. The expression of myelin basic protein was determined by immunohistochemistry and western blotting. Compared with the control group, latency and swimming distance were prolonged in the navigation test on days 2, 3, and 4 in the model group. In the spatial probe test on day 5, the number of platform crosses was reduced in the model group. Cristae cracks, swelling or deformation of mitochondria appeared in the hippocampus, the hippocampal H2S level was increased, the mitochondrial ATPase activity was decreased, and the expression of myelin basic protein in the hippocampus was down-regulated in the model group compared with the control group. All the above indexes were ameliorated in the aminooxyacetic acid remedy group compared with the model group. These findings indicate that aminooxyacetic acid can improve learning and memory in a chronic alcoholism rat model, which may be associated with reduction of hippocampal H2S level and mitochondrial ATPase activity, and up-regulation of myelin basic protein levels in the hippocampus.

Key words: nerve regeneration, aminooxyacetic acid, chronic alcoholism rat model, hydrogen sulfide, Ca2+ overload, brain injury, learning and memory abilities, Morris water maze, myelin basic protein, mitochondria, ATP enzyme activity, neural regeneration