低氧对小鼠学习记忆力及脑中tau蛋白磷酸化的影响

目的：研究不同低氧暴露对小鼠学习记忆及脑中tau蛋白磷酸化的影响。方法：雄性昆明小鼠40只，随机分为4组（n=10）：对照组（control）、8h低氧暴露组（8h）、7d低氧暴露组（7d）和28d低氧暴露组（28d）。将低氧暴露模型组置于模拟高原海拔5500m的低压氧舱，每天低氧暴露8h，避暗和旷场实验检测其活动能力及学习记忆能力：免疫印迹技术检测小鼠海马和皮层中tau蛋白磷酸化水平。结果：随着低氧时间的增加，小鼠短期学习记忆力及活动能力下降程度增大，28d低氧暴露后其下降程度最大；海马中tau蛋白多个位点的磷酸化水平呈现升高趋势，28d时tau蛋白磷酸化程度最高（P〈0．05）；皮层中的磷酸化水平在低氧暴露7d时达到最高，低氧暴露28d时略有降低，但与control组相比仍有明显差异（P〈0．05）。结论：慢性间歇性低氧可导致小鼠学习记忆能力下降，其机制可能与tau蛋白过度磷酸化相关。

Effect of hypobaric hypoxia exposure on memory and tau phosphorylation in brain of mice

Objective： To investigate the effect of hypobaric hypoxia （HH）on the cognitive function of mice and the phosphorylation of tau protein in mice brain. Methods： Forty male mice were randomly divided into 4 groups（ n = 10）： static control（control） group, 8 hours（8 h） group, 7 days（7 d） group and 28 days（28 d） group, which were exposed to simulated HH equivalent to 5 500 m in an animal decompression chamber for 0 hour, 8 hours, 7 days and 28 days, respectively. Cognitive performances were examined by open field and passive avoidance test, tau phesphorylation was assayed by Western blot. Results： In open field test, the group exposed in hypobaric hypoxia for 28 d showed lower mean velocity （ P 〈 0.05）, time in central zone （ P 〈 0.05） was longer than control group. In passive avoidance test 28 d group presented worse performance in both latency time and number of mistakes（ P 〈 0.05） compared with control group. Western blot showed that phesphorylated tau was increased significantly following exposure to HH for 7 d in cortex and 28 d in hippecampus （ P 〈 0.05）. Conclusion： Tan hyperphosphorylation in brain of mice may play a role in chronic HH-induced cognitive function impairment.