皮下注射碱性成纤维细胞生长因子促进血管性痴呆大鼠海马神经干细胞的增殖

Subcutaneous injection of basic fibroblast growth factors promotes the proliferation of hippocampal neural stem cells in rats with vascular dementia

背景:碱性成纤维细胞生长因子是一种神经营养因子,在中枢神经系统内广泛分布,可以与其相应受体结合,发挥重要的生理作用。目的:探讨皮下注射碱性成纤维细胞生长因子对血管性痴呆大鼠学习记忆能力和海马nestin阳性神经干细胞增殖的影响。方法:纳入30只SD大鼠,随机分为3组(n=10):血管性痴呆组、假手术组以及治疗组。血管性痴呆组和治疗组制备血管性痴呆模型,治疗组皮下注射碱性成纤维细胞生长因子。治疗后4周,采用Morris水迷宫实验检测大鼠的学习记忆能力,免疫组织化学染色检测海马nestin阳性细胞数的变化。结果与结论:(1)血管性痴呆组的潜伏期显著长于假手术组和治疗组,进出目标象限次数显著少于假手术组和治疗组(P<0.05)。假手术组和治疗组间比较,差异无显著性意义(P>0.05);(2)在荧光显微镜下,治疗组海马CA1,CA2,CA3区均可观察到带有黄绿色荧光的碱性成纤维细胞生长因子阳性神经元;(3)治疗组海马CA1区分布大量nestin阳性神经元,假手术组也分布较多nestin阳性神经元,血管性痴呆组nestin阳性神经元分布较为稀疏;(4)结果表明,皮下注射的碱性成纤维细胞生长因子能迁移至海马区,刺激海马nestin阳性神经干细胞增殖,进而改善大鼠学习记忆能力。

BACKGROUND： As a neurotrophic factor, basic fibroblast growth factors extensively distribute in the central nervous system, and play an important physiological role by combination with their relative receptors. OBJECTIVE： To investigate the effect of basic fibroblast growth factors on the learning ability and proliferation of nestin-positive hippocampal neural stem cells in rats with vascular dementia. METHODS： Totally 30 Sprague-Dawley rats were randomly divided into vascular dementia, sham operation and treatment groups. The vascular dementia and treatment groups were for preparing vascular dementia model, and the treatment group was given subcutaneous injection of basic fibroblast growth factors. Subsequently, at 4 weeks, the learning ability of rats and the number of nestin-positive hippocampal neural stem cells was detected by the Morris water maze test and immunohistochemical staining, respectively. RESULTS AND CONCLUSION： Compared with the vascular dementia group the latency period was significantly shorter in the sham operation and treatment groups, and the number of times crossing the target quadrant was significantly higher in the sham operation and treatment groups（P 0.05）. But there was no significant difference between the sham operation and treatment groups（P 0.05）. Under fluorescence microscope, yellow-green fluorescence stained neurons positive for basic fibroblast growth factor could be found in the CA1, CA2 and CA3 of the treatment group. Additionally, the number of nestin-positive neurons in the CA1 area of the hippocampus was the most in the treatment group, followed by the sham operation group, and the least in the vascular dementia group. These results suggest that the subcutaneous injection of basic fibroblast growth factors can migrate to the hippocampus,, and improve the learning ability of rats by inducing proliferation of nestin-positive hippocampal neural stem cells.