基质细胞衍生因子-1对神经干细胞移植治疗脊髓损伤大鼠疗效的影响

The effects of stromal cel1-derived factor 1 on the migration of neural stem cells and the recovery of lower limb function after spinal cord injury

目的 观察基质细胞衍生因子-1（SDF-1）对神经干细胞移植治疗脊髓损伤大鼠疗效的影响.方法 共选取96只成年健康雄性SD大鼠,应用改良Allen＇s打击法制成脊髓损伤大鼠模型,采用随机数字表法将其分为4组,分别是A组（于制模后7d时给予磷酸盐缓冲液注射）、B组（于制模后7d时给予神经干细胞移植）、C组（于制模后7d时联合给予SDF-1注射及神经干细胞移植）及D组（于制模后7d时给予AMD3100及神经干细胞移植）.于制模后7d、14 d、21 d及28 d时分别采用BBB运动功能评分对各组大鼠后肢运动功能进行评定,并于上述时间点对各组大鼠受损脊髓进行HE染色及CM-Dil荧光观察.结果 在制模后14d、21d及28 d时B组及C组大鼠受损脊髓区均能见到荧光标记阳性细胞聚集,上述时间点C组脊髓损伤区域阳性细胞数量[分别为（27.4±4.7）个、（20.4±5.2）个、（18.3±3.9）个]较B组细胞数量[分别为（23.6±3.7）个、（18.9±5.6）个、（15.2±4.3）个]显著增多（P＜0.05）.在制模后14d、21 d及28 d时B组BBB运动功能评分[分别为（4.18±0.87）分、（6.18±1.25）分、（9.27±0.91）分]及C组BBB运动功能评分[分别为（5.09 ±1.30）分、（8.18±0.75）分、（11.82 ±0.87）分]均较A组及D组显著改善（P＜0.05）,并且C组大鼠上述时间点BBB运动功能评分亦显著优于B组水平（P＜0.05）.结论 移植的神经干细胞能向大鼠受损脊髓部位迁移、存活并分化,能促进大鼠后肢运动功能恢复;SDF-1能诱导神经干细胞增殖并向脊髓损伤部位迁移,CXCR4受体阻断剂AMD3100能显著阻断神经干细胞向大鼠受损脊髓部位迁移.

Objective To assess the effect of stromal cell-derived factor 1 （SDF-1） on the migration of neural stem cells and recovery of lower limb function after spinal cord injury （SCI）.Methods A modified version of Allen＇s method was used to establish a SCI model in each of 96 adult male Sprague-Dawley rats.They were then randomly divided into group A which received an injection of phosphate buffer solution,group B which received an injection of neural stem cells,group C which received a combination of SDF-1 and neural stem cells,and group D which received AMD3100 and neural stem cells 7 days after the modeling.The functioning of the hind limbs of all of the rats was assessed on the 7th,14th,21st and 28th day after the modeling.The rats were then sacrificed and frozen sections of their spinal cords were stained with hematoxylin-eosin （HE） and marked with CM-Dil under fluorescent light.Results An accumulation of fluorescing cells were observed in spine cords from both group B and C,with the counts of group B [（23.6 ±3.7）,（18.9 ±5.6）and（15.2 ±4.3） respectively] at the day 14,21 and 28 after modeling significantly smaller than those of group C [（27.4 ± 4.7）,（20.4 ± 5.2） and （18.3 ± 3.9） respectively].During the same period of time,the average BBB scores of groups B and C were significantly better than those of groups A and D.Moreover,the average score of group C was significantly higher than group B＇s at all time points.Conclusions Transplanted neural stem cells can migrate to the injured site,surviving and differentiating to promote the recovery of limb function in rats with spinal cord injury.SDF-1 can promote that migration and proliferation.Moreover,CXCR4 receptor＇s antagonist AMD3100 can significantly hinder neural stem cells＇ migration to the injured site on the spinal cord.