BDNF基因修饰神经干细胞移植治疗脊髓损伤的实验研究

目的研究BDNF基因修饰神经干细胞移植对脊髓损伤后神经细胞凋亡的影响。方法采用电控大鼠脊髓损伤打击装置制作大鼠脊髓损伤模型。120只SD大鼠随机分为4组:假手术组(Sham组),脊髓损伤组(SCI组),神经干细胞组(NSC组),BDNF基因修饰神经干细胞组(NSC-BDNF组)。通过免疫组化法检测大鼠脊髓BDNF、Bax、Bcl-2的表达,流式细胞仪检测大鼠脊髓细胞凋亡率。结果NSC-BDNF组中BDNF免疫阳性细胞光密度值较NSC、SCI组增加明显(P<0.05),表达时间及表达高峰延长,且Bcl-2的表达较其他组在各个时间点上均增高(P<0.05),而Bax的表达较其他组在各个时间点上均降低(P<0.05),凋亡率亦明显低于NSC和SCI组(P<0.01)。结论BDNF基因修饰神经干细胞移植可引起BDNF在损伤脊髓内有效表达,且明显的促进了脊髓损伤后Bcl-2的高表达,抑制了Bax的表达,从而降低了神经细胞的凋亡率。

Effect of Implantation of Neural Stem Cell Modified by BDNF on Apoptosis of Neural Cells after Spinal Cord Injury

Objective To study the effect of implantation of neural stem cell(NSC)modified by brain-derived neurotrophic factor(BDNF)on the apoptosis of neural cells in rats with spinal cord injury(SCI).Methods The SCI model in SD rats were made by electrically controlled SCI device.One hundred and twenty rats were randomly divided into four groups,i.e.SCI group,Sham SCI group,the treatment group with NSC,and the treatment group with NSC modified by BDNF(NSC-BDNF).There were 30 rats in each group.The expressions of BDNF,Bax,and Bcl-2 were determined by immunohistochemical technique and the rate of apoptosis were detected by flow cytometry analysis.Results The significant increase in the expressions of BDNF,Bax,and Bcl-2 was induced by the SCI(P<0.05).The optical density(OD)of BDNF and Bcl-2 positive neuron increased significantly,and the OD of Bax positive neuron and the rate of neural cell apoptosis decreased significantly(P<0.01)in NSC-BDNF group compared to SCI and NSC groups(P<0.05).The OD of Bax positive neuron and the rate of neural cell apoptosis in NSC group were significantly lower than that in SCI group(P<0.05),but OD of the Bcl-2 positive neuron in NSC group was significantly higher than that of SCI group(P<0.05).Conclusion NSC modified by BDNF can reduce the neural cell apoptosis rate after the SCI.