丙戊酸影响神经干细胞体外分化的量效和时效关系

目的：研究丙戊酸（VPA）浓度和干预时间对神经干细胞（NSCs）体外分化的影响。方法：以不同浓度的VPA（0.1、0.3、0.5、0.75和1.0mmol/L）处理原代培养的神经干细胞,以NB培养基组做对照,分别于神经干细胞分化后3天、7天、10天和14天用免疫荧光双标鉴定并计数微管蛋白-Ⅲ（β-tubllin III）和胶质原纤维酸性蛋白（GFAP）阳性细胞的比例,并作统计学分析。结果：同一时相点组间比较,3天时各组中神经元分化比例无显著差异;7天时不同浓度VPA组与对照组分化神经元比例开始呈现差异;10天时这种差异继续增大,0.75 mmol/L VPA组中神经元比例为82.15±0.93%;14天时保持这种差异;但各时相点1.0 mmol/L VPA组与0.75 mmol/L VPA组神经元分化的比例无显著差异。不同时相点组内比较发现,3-10天内随着时间的延长,各组神经元分化的比例显著增加,但14天时神经元分化的比例较10天无显著变化。结论：0.75mmol/L VPA在10天时促神经干细胞向神经元分化的作用最佳。

The Dose and Time Effect of Valproic Acid on Differentiation of Neural Stem Cells

Objective：To investigate effect of valproic acid（VPA） with different dose and treated time on differentiation of neural stem cells（NSCs）.Methods：Different dose of VPA（0.1 mmol/L,0.3 mmol/L,0.5 mmol/L,0.75 mmol/L and 1.0mmol/L）were used to en-hance the differentiation of NSCs isolated and cultured in serum-free medium from the SD rats pregnant for 14 days.The NSCs in neural basal medium is the control group.Differentiated cells at 3rd day,7th day,10th day and 14th day were stained by DAPI,β-tubllin III and GFAP.And the ratio of differentiated cells was analysed.Results：The differentiated ratio of neurons at 3rd day had no disparity.At 7th day、10th day and 14th day the differentiated ratio of neurons in VPA groups was higher than that in control group.The differentiated ratio of neurons in 0.75 mmol/L VPA group was 82.15±0.93% at 10th day.But the differentiated ratio of neurons at 10th day and 14th day had no disparity.At 3 to 10 days the differentiated ratio of neurons in each group increased apparently,but at 14th day the differenti-ated ratio in each group didn＇t increased.Conclusion：0.75 mmol/L VPA at 10th day produces the best effect on promoting the NSCs dif-ferentiated into neurons.