胰岛素样生长因子-1抑制β淀粉样蛋白25-35诱导的神经干细胞凋亡

INSULIN-LIKE GROWTH FACTOR-1 PROTECTS NEURAL STEM CELLS FROM APOPTOSIS INDUCED BY β-AMYLOID PEPTIDE_(25-35)

目的 观察β-淀粉样蛋白（Aβ）对神经干细胞（NSCs）增殖和凋亡的影响，探讨胰岛素样生长因子-1（IGF-1）对Aβ介导的NSCs毒性作用的保护机制。方法 从E14SD大鼠大脑中分离神经干细胞，分别用Aβ、IGF-1和卸加IGF-1处理，锥虫蓝（trypan blue）染色确定细胞死亡数量和细胞死亡率，BrdU标记并分析细胞增殖能力，免疫细胞化学法鉴定神经干细胞和新生细胞，TUNEL技术检测凋亡细胞。结果 IGF-1处理时细胞死亡率低下，有大量BrdU阳性细胞生成，但无TUNEL阳性细胞。Aβ处理组细胞死亡率在6～48h快速上升，并形成大量TUNEL阳性细胞。而IGF-1加Aβ处理时，细胞死亡率较Aβ组显著下降。TUNEL阳性细胞显著减少。结论 Aβ促进神经干细胞死亡和凋亡；而IGF-1促进神经干细胞增殖并抑制由Aβ诱导的神经干细胞凋亡。

Objective To observe the influences of β-amyloid peptide（Aβ） on the proliferation and apoptosis of neural stem ceils（NSCs） and to investigate the protective mechanism of insulin-like growth factor-1 （IGF-1） from toxicity of Aβ. Methods NSCs were isolated from E14 SD rats brains and then treated with IGF-1, Aβ and IGF-1 plus Aβ respectively. The cells were dyed with trypanblue for the count of dead cells and the death rate. BrdU was used to label cells and to evaluate cell proliferation. NSCs and newborn cells were identified by immunocytochemistry and apoptosis was detected by TUNEL technique. Results Cell death rate was low and there were many BrdU-positive cells, but no TUNEL-positive cells in the medium containing IGF-1. Cell death rate increased strikingly 6-48 hours after Aβ was added, and a great many TUNEL-positive cells were observed in the group treated with Aβ. Death rate of cells and TUNEL-positive cells decreased more markedly in the medium containing both IGF-1 and Aβ than that containing Aβ only. Conclusion Aβ promotes death and apoptosis of NSCs, while IGF-1 accelerates the proliferation of NSCs and inhibits NSCs apoptosis induced by Aβ.