低氧诱导因子-1α基因促进大鼠局灶性脑缺血后神经干细胞的增殖和分化

目的观察低氧诱导因子-1α(HIF-1α)基因对大鼠局灶性脑缺血后内源性神经干细胞(NSCs)增殖和分化的影响,并探讨HIF-1α对内源性NSCs增殖分化的作用机制。方法建立大鼠大脑中动脉缺血再灌注模型,分为假手术组(sham)、生理盐水组(NS)、腺病毒空载体组(AD)及携带HIF-1α基因的重组腺病毒组(Ad-HIF-1α)。分别将NS、AD和Ad-HIF-lα注射到模型鼠缺血侧侧脑室,观察4组大鼠神经功能缺失评分;免疫组织化学法观察4组大鼠局灶性脑缺血后缺血灶周围促红细胞生成素(EPO)的表达;免疫荧光法计数再灌注不同时间点室管膜下区(SVZ)BrdU阳性细胞(3d、7d、14d、21d、28d)和皮层BrdU/NF200、BrdU/GFAP(28d)阳性双标细胞。结果Ad-HIF-lα组神经功能缺失评分与AD组和NS组比较,结果有统计学差异;EPO表达增强;Ad-HIF-lα组BrdU标记细胞数明显增加;新生细胞分化结果显示,28d时Ad-HIF-lα组BrdU/NF200(47.74±13.52)%、BrdU/GFAP(67.83±20.75)%,与其他组相比均有显著性差异(P<0.05)。结论低氧诱导因子-1α基因可促进大鼠局灶性脑缺血后内源性NSCs的增殖与分化,从而促进神经功能的恢复。

EFFCT OF HYPOXIA-INDUCIBLE FACTOR-1α GENE ON THE PROLIFERATION AND DIFFERENTIATION OF NSCs AFTERFOCAL CEREBRAL ISCHEMIA IN RATS

Objective To investigate the effect of hypoxia inducible factor-1α gene on the proliferation and differentiation of neural stem cells after focal cerebral ischemia in rats, and to explore the mechanism of the effect. Methods Middle cerebral artery occlusion(MCAO) and reperfusion models were established and divided into sham group, NS group, AD group and Ad HIF-lα group. NS, AD and Ad-HIF-lα were injected into the ischemic ventricle respectively. The mNSS was evaluated the expression of EPO was observed, and the number of BrdU positive cells in subventricular zone and that of BrdU／NF200， BrdU／GFAP double labeled cells in cortex were calculated by immumofluorescence method. Results The mNSS were statistically different between Ad-HIF-lα group and the other three groups; the expression of EPO was higher in Ad-HIF-lα group; the number of BrdU positive cells increased obviously in Ad-HIF-lα group; the cellular rebirth and differentiation demonstrated that there existed a significant difference (P<0.05) in the numbers of BrdU／NF200