慢性缺氧对成年小鼠海马区神经发生的影响

The effects of chronic ischemia on hippocampal neurogenesis of adult mice

目的通过观察慢性缺氧对成年小鼠海马区神经发生的影响,探讨脑卒中导致的血管性痴呆的发病机制。方法利用海马区神经干细胞慢性缺氧模型,通过神经干细胞形态变化观察及直径测量、TUNEL染色和免疫细胞化学染色等方法,评价慢性缺氧对神经干细胞形态、增殖能力、分化能力及凋亡的影响。结果随着缺氧时间延长,低氧组神经干细胞球结构破坏明显,增长停滞。神经干细胞球直径测量结果显示:正常组与第0天直径(130.30±5.74)μm相比,第3天直径(195.62±20.18)μm、第7天直径(247.43±32.97)μm及第12天直径(298.97±39.59)μm均明显增长(P<0.05);而低氧组神经干细胞球直径在不同时间点差异均无统计学意义(P>0.05)。TUNEL染色结果发现,缺氧组神经干细胞有明显TUNEL阳性表达。免疫细胞化学染色结果显示:缺氧组中,偶见神经干细胞表达Nestin蛋白,而GFAP蛋白表达明显增强。结论慢性缺氧影响成年小鼠海马区的神经发生,这可能是脑卒中血管性痴呆的发病机制之一。

Objective To explore the possible mechanisms of ischemia induced vascular dementia by evaluating the affection of chronic ischemia on hippocampal neurogenesis of adult mice. Methods Chronic ischemia model were setting up in vivo, the morphology of the neurosphere was observed, the proliferation ability of the neurosphere was evaluated by diameter measure;the apoptosis of the neu- rosphere was test by TUNEL staining; the differentiation ability of the neurosphere was examined by immune - cytostaining. Results Compared with the neurosphere in the normal control group, the neurosphere in the ischemic group seemed stopped to prolifera- tion and its structure was destroyed. The TUNEL positive cell number was more in ischemic group than that in normal control group. The expression of nestin was lower in ischemic group than that in normal control group, but the expression of GFAP was more in ischemic group than that in normal control group. Conclusion Chronic ischemia may has effects on hippocampal neurogenesis of adult mice, which might be one of the mechanisms of ischemia induced vascular dementia.