骨形成蛋白4对脊髓损伤后大鼠功能和神经干细胞的影响

目的　观察骨形成蛋白 4对脊髓损伤后大鼠功能和神经干细胞的影响。方法　应用改良Allen脊髓损伤模型 ,将成年SD大鼠 6 0只随机分为BMP 4组、脊髓损伤组。分别于术后 1d、7d、14d、2 1d、2 8d处死动物 ,并且对大鼠进行Tarlov评分和斜板试验检查后肢功能。应用免疫组织化学技术检测巢蛋白 (nestin)的表达 ,观察BMP4对脊髓损伤后nestin表达的影响。结果　第 2 1d时BMP4组大鼠功能改善明显与损伤组比较差异有显著性意义 (P <0 0 5 ) ;脊髓损伤后第 1天 ,在BMP4组和脊髓损伤组的室管膜、室管膜下区、损伤脊髓灰质中都可见到nestin的表达。于损伤后迅速增加 ,第 14天时达到高峰。BMP4组灰质nestin表达为 15 35± 3 83,脊髓损伤组灰质为 8 4 8± 3 5 3,两者差异有显著性 (P <0 0 1)。BMP4组可使损伤的脊髓中nestin持续高表达至术后第 2 8天 ,而脊髓损伤组仅持续表达至术后 2 1d。增加的nestin阳性细胞数与神经功能的改善平行。结论　提示BMP4可减轻神经损伤症状和对脊髓损伤后神经干细胞有促进增殖作用。

Effect of bone morphogenetic protein 4 on the function in the rats and the neural stem cell following injured spinal cord

Objective To investigate the effect of BMP4 on neural stem cell following injured spinal cord as well as functional recovery in the rats. Methods Sixty adult SD rats were randomly divided into BMP4 therapy group and spinal cord injury group. After operation open field and inclined plane texts were performed to test the function of the rear limbs. The animals were sacrificed 1,7,14,21 and 28 day after surgery. The expression of the nestin was detected by immunohistochemical method to observe the effects of BMP4 therapy on neural stem cell following injured spinal cord. Results There was significant difference between the two groups in the function of the rear limbs at 21 day after spinal cord injury (P<0.05).The nestin positive expression cells were detected in the subventricular zone and gray matter one day after spinal cord injury(SCI). The nestin positive expression cells increased rapidly after operation and reached their peak at day 14 after SCI in both group; the number of the nestin positive expression cells in the grey matter in BMP4 therapy group was 15.35±3.83, that in spinal cord injury group is 8.48±3.53,P<0.05. The positive cells in BMP4 therapy group maintained at high level to day 28; however, the positive cells in spinal cord injury group decreased significantly at 21 day. The increase in the nestin positive cells was paralleled by a significant improvement in motor function evaluated by open field and inclined plane text. Conclusion BMP4 therapy can enhance the motor function of the rear limbs and promote the proliferation of neural stem cell following spinal cord injury in rats.