中文摘要：

目的研究低氧诱导因子-1α（HIF-1α）基因转导的神经干细胞（NSCs）移植对大鼠脊髓损伤（SCI）后红核神经元损伤的影响。方法采用电控SCI打击装置制作大鼠SCI模型。将80只SD大鼠随机分为4组：对照组、SCI组、NSCs组、基因修饰移植组（HIF-NSC组）。5-溴脱氧尿嘧啶核苷（BrdU）法标记处于对数生长期的NSCs,SCI后即刻进行NSCs及HIF-1α基因转导的NSCs移植。应用免疫组化法观察BrdU标记的移植细胞的存活、迁移情况以及HIF-1α的表达,用辣根过氧化物酶（HRP）逆行示踪技术标记红核神经元,用四甲基联苯胺（TMB）呈色反应显示红核脊髓束神经元的存活情况,采用斜板试验（改良Rivlin法）观察大鼠后肢运动功能的恢复情况。结果 NSCs组与HIF-NSC组在损伤脊髓区域均可检测到BrdU标记的阳性NSCs;HIF-NSC组中HIF-1α免疫阳性细胞平均光密度（OD）值比其他各组各时间点均高（P〈0.01）,且表达高峰延迟至移植后14d;中脑HRP标记红核神经元数目明显多于NSCs组、SCI组（P〈0.01）;移植后第7、14、28天,HIF-NSC组后肢运动功能评分比NSCs组、SCI组明显升高（P〈0.01）。结论 HIF-1α基因体外转导的胚鼠NSCs移植到SCI区域后可以存活、迁移,且能明显的上调HIF-1α的表达、减轻红核神经元的逆行性损伤,从而促进大鼠后肢运动功能的恢复。

英文摘要：

Objective To study the effects of hypoxia inducible factor-1a（HIF-1a） genetically modified neural stem cells transplantation on trauma of red nucleus neurons in the rats with spinal cord injury（SCI）. Methods SCI model of Sprague Dawley rats was induced with electrocircuit control spinal cord injuring device. 80 SD rats were divided into four groups randomly., normal group, SCI group,NSC group and HIF-NSC group. The NSCs labeled with BrdU were transplanted into the injured site on 3 d after SCI. HIF-1a and BrdU were detected by immunohistochemisty, rubrospinal tract（RST） neurons were labeled by retrograde trans- port of the horseradish peroxidase（HRP） from the lesion site, which were taken by damaged axons and remained in the neurons, then the labeled red nucleus（RN） neurons were counted. The improved Rivlin method（slope test） was used to assess the motor function following spinal cord injury in rats. Results NSCs can be detected in the spinal cord after transplantation. The mean OD of HIF-la in HIF-NSC group was prominently higher than that of the other experimental groups at each time point（P〈0.01）. The expression peak was postponed to 14 d after transplantation. The number of RST neurons labeled by HRP in HIF-NSC group wasore than that in SCI and NSC group（P〈0.01）. On 7,14,28 d after transplantation,the scores of hindlimb motor function were obviously increased compared with the NSCs and SCI groups（P〈0.01）. Conclusion HIFla genetically modified NSCs can survive in the injured site of spinal cord,upregulate more obviously the expression of HIF-1a and protect RN, then promote more remarkably functional recovery of hind limb in rat after SCI.