碱性成纤维细胞生长因子促进脊髓损伤小鼠内源性神经干细胞的增殖  

Basic fibroblast growth factors promote proliferation of endogenous neural stem cells after spinal cord injury in mice

作　　者：李宇博[1] 丁立祥[2] 

机构地区：[1]首都医科大学附属北京朝阳医院骨科,北京市100020 [2]首都医科大学附属北京世纪坛医院脊柱外科,北京市100038

出　　处：《中国组织工程研究》2016年第23期3476-3483,共8页Chinese Journal of Tissue Engineering Research

基　　金：国家自然科学基金青年项目(31300923)~~

摘　　要：背景:目前对于脊髓损伤的治疗主要以激素冲击及手术解除压迫为主,但是对已损伤的神经元无特效疗法。神经生长因子及内源性神经干细胞的应用,可以使神经元再生、轴突再髓鞘化,为脊髓损伤的治疗提供了新思路。目的:探讨碱性成纤维细胞生长因子对脊髓损伤后内源性神经干细胞增殖的影响及其与荧光金标记神经元数量增加的相关性。方法:昆明小鼠48只随机分为正常组、脊髓损伤组、治疗组、假手术组。脊髓损伤组、治疗组建立急性脊髓损伤模型,正常组仅实施手术而不损伤脊髓,在脊髓损伤后恢复意识2 h起开始,治疗组每日腹腔内注射溶有碱性成纤维细胞生长因子(25μg/kg)的含1%白蛋白的MTPBS。在第7天对前3组小鼠再次实施手术,于L1节段置入浸润荧光金的无菌明胶海绵,假手术组不进行处理。运用Rotarod和Platform Hang实验对小鼠的运动能力进行测试,使用荧光金对小鼠皮质脊髓束和红核脊髓束中的神经元进行标记计数,通过免疫组化检测nestin阳性内源性神经干细胞的数量,同时分析荧光金标记的神经元数量与内源性神经干细胞数量间的相关性。结果与结论:(1)碱性成纤维细胞生长因子可显著改善受伤小鼠的运动功能,经碱性成纤维细胞生长因子处理后内源性神经干细胞数量明显升高,且与荧光金标记的神经元数量的增加存在相关性;(2)结果表明,碱性成纤维细胞生长因子在脊髓损伤后内源性神经干细胞的增殖过程中起着重要作用,而内源性神经干细胞通过增加再生神经元的数量使运动功能得到恢复。BACKGROUND： So far steroid pulse therapy and surgical decompression are the main accepted therapies for spinal cord injury, but these methods make no effects on injured neurons. Nerve growth factors and endogenous neural stem cells play a role in the neuronal regeneration and remyelination, which provides a new idea for spinal cord injury treatment. OBJECTIVE： To explore the effect of the basic fibroblast growth factor on proliferation of endogenous neural stem cells after spinal cord injury and to analyze its relationship with the increased fluoro-gold labeled neurons. METHODS： Totally 48 Kunming mice were randomly divided into four groups including normal, spinal cord injury, treatment and sham operation groups. Acute spinal cord injury models were established in the spinal cord injury and treatment groups, and the normal group was subjected to operation that did not damage the spinal cord. At 2 hours after regaining consciousness, the treatment group was given daily injection of MTPBS containing 25 μg/kg basic fibroblast growth factors and 1% album. And at 7 days, laminectomy was carried out again at the L1 segment in the former three groups and a small piece of sterile gelfoam soaked with fluoro-gold was inserted into the incision. The sham operation group was given no processing. Afterwards, mouse motor behavior was assessed using Rotarod and Platform Hang tests; neurons in the corticospinal and rubrospinal tracts were labeled with fluoro-gold; the number of endogenous neural stem cells positive for nestin was detected by immunohistochemistry method. Besides, the correlation between the number of fluoro-gold labeled neurons and the number of endogenous neural stem cells was assessed. RESULTS AND CONCLUSION： The basic fibroblast growth factor could significantly improve the mouse motor behavior after spinal cord injury. And the number of endogenous neural stem cells was significantly increased after the basic fibroblast growth factor injection, which was related to the increased fluoro-gold labeled n

关 键 词：脊髓损伤 成纤维细胞生长因子2 神经干细胞 组织工程 干细胞 神经生长因子 碱性成纤维细胞生长因子 内源性神经干细胞 国家自然科学基金 

分 类 号：R394.2[医药卫生—医学遗传学]