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张 泓,黄桂兰,谭 洁,黎 帅,邓多喜,刘桐言,刘家庆,郭奎奎,肖 瑶.有氧运动对慢性缺血性认知障碍模型大鼠海马组织pCREB、PICK1及GluR2蛋白表达的影响[J].中国康复医学杂志,2018,(7):777~782
有氧运动对慢性缺血性认知障碍模型大鼠海马组织pCREB、PICK1及GluR2蛋白表达的影响    点此下载全文
张 泓  黄桂兰  谭 洁  黎 帅  邓多喜  刘桐言  刘家庆  郭奎奎  肖 瑶
湖南中医药大学,湖南长沙,410208
基金项目:湖南省教育厅优秀青年项目(16B197);湖南省“十二五”重点学科针灸推拿学开放基金重点资助项目(2015-02)
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摘要:
      摘要 目的:观察有氧运动对慢性缺血性认知障碍模型大鼠学习记忆能力及海马组织中磷酸化环磷腺苷反应元件结合蛋白(pCREB)、蛋白激酶C相互作用蛋白1(PICK1)及谷氨酸受体2(GluR2)表达的影响,探讨其部分作用机制。 方法:56只SD雄性大鼠按照随机数字表法分成4组,假手术组、模型组、药物组及有氧运动组,每组14只。模型组、药物组及有氧运动组按照双侧颈总动脉永久结扎法制备模型,所有大鼠于造模前、造模后及治疗后进行3次Morris水迷宫评估,运用尼氏染色法观察海马CA1区病理形态学改变、Western Blot法测定大鼠海马组织pCREB、PICK1及GluR2蛋白的表达情况。 结果:①Morris水迷宫评估结果显示:与假手术组比较,模型组的平均逃逸潜伏期时间明显延长、平台搜索次数显著减少(P<0.01);与模型组比较,有氧运动组及药物组大鼠找到平台所需时间减少(P<0.01),平台搜索次数增加(P<0.05,P<0.01);而有氧运动组和药物组比较,无显著性意义(P>0.05)。②尼氏染色光镜下,模型组、有氧运动组及药物组尼氏小体数量减少,排列紊乱疏松,细胞结构出现不同程度的损害,而有氧运动组及药物组损害较模型组轻。③Western Blot法测定结果显示:模型组大鼠海马组织pCREB、GluR2蛋白表达含量与假手术组相比明显减少(P<0.01),PICK1蛋白表达量明显增加,差异均有显著性意义(P<0.01);与模型组相比,有氧运动组和药物组大鼠海马组织pCREB(P<0.01,P<0.05)、GluR2蛋白表达量均增加(P<0.05,P<0.01),PICK1蛋白表达量均明显减少(P<0.01);而有氧运动组和药物组在以上蛋白表达上无差异(P>0.05)。 结论:有氧运动能有效提高慢性缺血性认知障碍大鼠的学习、记忆能力,其治疗效果与单唾液酸四己糖神经节苷脂钠注射液相当。上调海马组织内pCREB、GluR2蛋白,下调PICK1蛋白的表达可能是其治疗慢性缺血性认知障碍的部分机制之一。
关键词:有氧运动  认知障碍  血管性痴呆  模型大鼠
Effects of aerobic exercise on the expression of PCREB, PICK1 and GluR2 proteins in hippocampus of rats with ischemic cognitive impairment    Download Fulltext
Hunan University of Traditional Chinese Medicine, 410208
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Abstract:
      Abstract Objective: To investigate the influence of aerobic exercise on memory ability and the expression of pCREB,PICK1 and GluR2 on hippocampus in rats with ischemic cognitive disorder. Method: Fifty-six male Sprague-Dawley rats were randomly divided into four groups: sham-operation group,model group,medicinal group and aerobics group according to the numeration table(n=10 in each group). In model group,medicinal group and aerobics group,common carotid arteries were ligated to establish the model.All groups were evaluated by Morris water maze three times,before the models,after the models and after the treatment.The pathomorphological changes of CA1 areas in hippocampus was observed by Nissl staining and the impression of pCREB,PICK1 and GluR2 was also measured by Western Blot. Result:①Morris water maze assessment showed,The average escape latency was significantly longer and the platform search frequency decreased significantly in model group than in sham-operation group(P<0.01).The required time to find the platform(P<0.01)and the platform search frequency(P<0.05,P<0.01)was shorter in aerobic exercise group and medicinal group than in model group,but there was no significant difference between aerobic exercise group and medicinal group(P>0.05).②The number of Nissl bodies in the neurons decreased,the arrangement was chaotic and loose and the cell structure was damaged in different degrees in model group,aerobic exercise group and medicinal group.The damage in aerobic exercise group and medicinal group was lighter than in model group.③Western Blot assessment showed,The pCREB and GluR2 protein levels was significantly lower and GluR2 protein levels was significantly higher in model group than in sham-operation group(P<0.01).Compared with the model group, the expressions of pCREB and GluR2 protein in the hippocampus of the aerobic exercise group and the medicinal group were increased(P<0.01,P<0.05),The expression of PICK1 protein decreased obviously(P<0.01).But there was no significant difference between aerobic exercise group and medicinal group(P>0.05). Conclusion:The aerobic exercise can effectively enhance the learning and memory ability of rats with chronic ischemic cognitive disorder,The therapeutic effect is comparable to that of single sialic acid and four hexose ganglioside sodium injection.The up-regulated expression of pCREB and GluR2 and The down-regulated expression of PICK1 may be one of the mechanisms in the treatment of chronic ischemic cognitive impairment.
Keywords:aerobic exercise  cognitive impairment  vascular dementia  model rats
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