神经干细胞移植治疗大鼠恢复期脊髓损伤

Neural stem cell transplantation for the treatment of rat spinal cord injury in recovery period

背景:研究发现,脊髓损伤后细胞外信号调节激酶在反应性胶质细胞中存在上调现象,且磷酸化的细胞外信号调节激酶急剧增多。目的:验证神经干细胞移植对恢复期脊髓损伤大鼠的功能影响及其在病灶局部的分化及机制。方法:90只SD大鼠被随机分为3组,每组30只。对照组大鼠造模但不进行神经干细胞移植;静脉移植组及局部移植组造模后分别进行神经干细胞移植,分别于移植后的1,2,4,12,24周对各组随机抽取的6只动物后肢功能进行BBB评分及免疫组织化学染色。结果与结论:神经干细胞移植后,静脉移植组和局部移植组病灶局部可见Brdu阳性细胞;大鼠BBB评分逐渐提高,移植4周后静脉移植组和局部移植组BBB评分明显高于同期对照组;大鼠脊髓胶质纤维酸性蛋白、细胞外信号调节激酶1/2逐渐提高,4周达最大值,移植12周后胶质纤维酸性蛋白、细胞外信号调节激酶1/2较同期减少(P<0.05);微管相关蛋白2逐渐提高,4周达最大值,4周以后呈下降趋势,12周后不再有明显变化,但微管相关蛋白2较同期对照组增多(P<0.01)。结果提示,神经干细胞移植后可在病灶局部增殖分化为神经元和神经胶质细胞;两种移植方式的作用没有明显区别;神经胶质细胞再生的过程和细胞外信号调节激酶通路密切相关。

BACKGROUND：Studies have found that extracel ular signal-regulated kinase can up-regulate the reactive glial cel s after spinal cord injury, and the number of phosphorylated extracel ular signal-regulated kinase is increased. OBJECTIVE：To evaluate the effect of neural stem cel transplantation on motor function recoveryof rats with spinal cord injury in the recovery period, and to explore the focal differentiation and mechanism. METHODS：Ninety Sprague Dawley rats were randomly divided into three groups, 30 rats in each group：control group, local transplantation group and intravenous infusion group. Rats in the control group were used to establish the models but did not receive neural stem cel transplantation;rats in the local transplantation group and the intravenous infusion group received neural stem cel transplantation after modeling. Six rats were col ected from each group;then Basso, Beattie and Bresnahan score and immunohistochemical staining were performed at 1, 2, 4, 12 and 24 weeks after transplantation. RESULTS AND CONCLUSION：After neural stem cel transplantation, Brdu positive cel s could be seen in local lesions of local transplantation group and the intravenous infusion group;Basso, Beattie and Bresnahan score at 4 weeks after transplantation in the local transplantation group and the intravenous infusion group was significantly higher than that in the control group;levels of rat spinal cord glial fibril ary acidic protein and extracel ular signal-regulated kinase 1/2 were gradual y increased and reached peak at 4 weeks after transplantation;at 12 weeks after transplantation, the levels of spinal cord glial fibril ary acidic protein and extracel ular signal-regulated kinase 1/2 were decreased （P〈0.05）;the level of microtubule-associated protein 2 was increased and reached peak at 4 weeks after transplantation, and gradual y decreased after 4 weeks;at 12 weeks after transplantation, there was no significant difference in microtubule-associated protein 2 level, but the microtubule-associated protein 2 level was higher than that in the control group （P〈0.01）. After neural stem cel transplantation, the neural stem cel s could proliferate and differentiate into neuron and neuroglial cel s. There is no significant difference between the two methods. There may be a certain correlation between the glial cel s regeneration process and extracel ular signal-regulated kinase pathways.