褪黑素促进体外缺氧的神经干细胞增殖及定向分化

Effect of Melatonin on Proliferation and Differentiation of Neural Stem Cells after Hypoxia in vitro

目的:观察褪黑素对体外缺氧诱导的小鼠神经干细胞(neural stem cells,NSCs)增殖和分化的影响。方法:取孕12.5 d胚胎小鼠大脑皮质分离培养NSCs,建立缺氧模型。利用免疫荧光染色,检测分析褪黑素对缺氧诱导后不同时间点的NSCs增殖和分化的影响。结果:缺氧后NSCs的增殖能力明显下降,而褪黑素可显著改善这一现象,促进缺氧后NSCs的增殖。缺氧后NSCs向神经元的分化明显受阻,褪黑素处理组的神经元的分化率明显高于对照组,其中作用高峰期是分化的第七天。结论:体外缺氧的NSCs增殖和分化均明显受到抑制,而褪黑素的干预可明显改善干细胞的增殖,促进NSCs向神经元的分化,但对星形胶质细胞的分化没有显著影响。

Objective： To observe the effects of melatonin on proliferation and differentiation of neural stem cells （NSCs） after hypoxia in vitro. Methods： The NSCs dissected from E12.5 day mouse brain and hypoxia in vitro model was esxablishal. We then examined the effect of melatonin on the proliferation and differentiation of hypoxic NSCs in vitro via immunohistochemistry. Results： Hypoxia decreased the proliferation of NSCs, but melatonin treatment could make it inverse and stimulated the proliferation of hypoxic NSCs. Hypoxia inhibited the differentiation of NSCs to neurons, but the percentage of neurons in all melatonin treated groups increased, especially at the 7th day. When compared with the controis, hypoxia did not affect the differentiation of NSCs into astrocytes. In melatonin-treated groups, NSCs differentiation into astrocytes remained unchanged. Conclusion： Our data suggests that melatonin treatment on NSCs in hypoxia is a potential strategy that increase proliferation and neuronal differentiation without affecting astroglial differentiation.