模拟高原低氧对大鼠皮质和海马神经颗粒素表达的影响

Expression of neurogranin of hippocampus and cortex in rats exposed to simulated high altitude hypoxia

目的:分析高原低氧环境对大鼠大脑皮质、海马神经颗粒素表达的影响以及与学习记忆的关系。方法:实验于2005-01/07在中国协和医科大学基础医学院病理生理学系实验室进行。取成年健康雄性Wistar大鼠20只,随机分成对照组和模拟高原低氧组,每组10只。置于模拟海拔5000m高度的低压舱内4周,复制慢性高原低氧动物模型。低氧结束后进行Morris水迷宫实验,测试大鼠空间学习记忆能力的改变。采用反转录-聚合酶链反应和Westernblot方法分别检测皮质和海马中神经颗粒素mRNA水平和蛋白水平的表达。结果:大鼠20只全部进入结果分析,无脱失值。①模拟高原低氧组的逃避潜伏期明显低于对照组,差异有显著性[(32.70±5.01),(51.30±7.11)s,t=6.76,P<0.01]。②神经颗粒素mRNA在大鼠皮质、海马中均有表达。与对照组相比,皮质组织中神经颗粒素mRNA在4周低氧后明显下降,差异有显著性[(1.39±0.19),(0.98±0.20),t=3.351,P<0.01],而海马中组织内神经颗粒素mRNA的水平与对照组接近,差异无显著性[(1.33±0.42),(1.16±0.27),P>0.05]。③两组大鼠皮质,海马的神经颗粒素均有表达,慢性低氧后模拟高原低氧组皮质中神经颗粒素比对照组明显降低,差异有显著性[(96.32±7.50),(57.23±13.41),t=7.307,P<0.01]。而海马中神经颗粒素在两组间未见明显变化[(53.29±8.33),(42.49±19.19)P>0.05]。结论:模拟高原低氧环境使大鼠空间学习记忆能力明显下降,大脑皮质中神经颗粒素mRNA水平和蛋白水平显著降低,而海马中则无明显变化。高原低氧环境下大鼠空间学习记忆能力的下降,可能与皮质中神经颗粒素表达的减少有关。

AIM： To analyze the influence of high-altitude hypoxia on the expression of cerebral cortex, hippocampus neurogranin in rats in relation to learning and memory abilities. METHODS： The experiment was carried out in the Laboratory of Department of Pathophysiology, School of Basic Medicine, Peking Union Medical College from January to July 2005. A total of 20 male Wistar rats were randomly divided into control group and simulated high-altitude hypoxia group with 10 rats in each group. All rats exposed to simulated high-altitude of 5000 meters for 4 weeks, then chronic high-altitude hypoxia models were duplicated. Morris water maze experiment was conducted after exposure to hypoxia, changes of learning and memory abilities in rats were detected. RT-PCR and Western blot method were used to detect levels of neurogranin mRNA and cortex as well as the expression of protein in rats. RESULTS： A total of 20 rats were involved in the analysis of results, no rat withdrew from the experiment. ① Escaping latency in the simulated high-altitude hypoxia group was significantly shorter than that in the control group, and differences were obvious [（32.70±5.01 ）, （51.30±7.11 ）s, t=6.76,P 〈 0.01]. ②Neurogranin mRNA had expressions in cortex and hippocampus. Compared with control group, hypoxia in neuregranin mRNA of cortex was significantly decreased after 4 weeks, and differences were significant [（ 1.39±0.19 ）,（0.98±0.20）,t=3.351 ,P〈 0.01], while it was similar with that in the control group, differences were not obvious [（1.33±0.42）, （1.16±0.27） ,P 〉 0.05]. ③ Neurogranin of cortex and hippocampus all had expressions in rats of both groups, and neurogranin in the control group was significantly higher than that in the other group, and differences were obvious [（96.32±7.50）, （57.23±13.41）,t=7.307,P〈 0.01], whereas, there were no significant changes in neurogranin of hippocampus between the two groups[（53.29±8.33 ）, （42.49±19.19）P 〉 0.05]. CONCLUSION： The spatial memory ability of rats Were significantly decreased under simulated high-altitude hypoxia, level of neurogranin mRNA and protein decreased obviously, while no significant changes were found in hippocampus. The decreasiing of spatial memory ability in rats under simulated high-altitude hypoxia may related with the decreasing of neurogranin expression in the cortex.