高原低氧环境下小鼠皮层神经元自噬与凋亡的相关性研究

Correlation between neuronal autophagy and apoptosis in mouse cortex after high-altitude hypoxia treatment

目的观察6000 m海拔高度下不同时长的高原低氧暴露对小鼠皮层神经元自噬及凋亡的影响,探讨其相关性。方法 40只C57BL/6小鼠随机分为平原对照组及不同时长(1 d、3 d、7 d、14 d)的高原低氧处理组,每组8只。模拟6000 m海拔的高原低氧环境,实验组分别给予1 d、3 d、7d、14 d的高原低氧处理,对照组饲养于舱外。采用Western Blot检测低氧诱导因子-1α(HIF-1α)及自噬标志物Beclin-1、微管相关蛋白1轻链3-II(LC3-II)在皮层组织的表达;赫斯特荧光染料33342(Hoechst 33342)染色用于观察皮层神经元的凋亡改变。结果与平原对照组相比,不同时长的高原低氧处理增加了小鼠皮层组织HIF-1α、Beclin-1及LC3-II的表达,同时明显增加了皮层神经元的凋亡率。结论高原低氧环境下,自噬的激活可能是小鼠皮层神经元凋亡发生的重要原因,而HIF-1α在该过程中可能发挥了重要的调控作用。

Objective Effect of high-altitude （6000 m） hypoxia exposure for different duration on neuronal autophagy and apoptosis in mouse cortex was investigated, and the correlation between them was discussed. Methods Forty C57BL/6 mice were randomly divided into five groups： control group, and 1 d, 3 d, 7 d, 14 d high-altitude hypoxia exposure groups. High-altitude hypoxia circumstances （6000 m） was mimicked by hypobaric oxygen chamber. Then all the experimental groups were subjected to high-altitude hypoxia treatment for different durations, whereas the control group was kept only outside the chamber. Expressions of hypoxia-inducible factor lot （HIF-1α） and autophagy marker proteins-Bcelin-1 and microtubule-associated protein 1 light 3-Ⅱ （LC3-Ⅱ） were detected by Western Blot. Hoechst 33342 staining was used to observe the neuronal apoptosis in mouse cortex. Results Compared with control group, the expressions of HIF-1α, Bechn-1 and LC3-Ⅱ were significantly increased after high-altitude hypoxia exposure for different time. Meanwhile, neuronal apoptosis rates in mouse cortex were also increased after high-altitude hypoxia treatment. Conclusion Activation of autophagy may lead to neuronal apoptosis in mouse cortex after high-altitude hypoxia exposuure and HIF-1α may play a regulatory role in this process.