骨髓间充质干细胞移植脑出血模型大鼠血肿周围轴突生长抑制因子MAG及OMgp的表达*

背景：中枢神经系统损伤后轴突再生困难与损伤灶周围高表达轴突生长抑制因子Nogo-A、MAG、OMgp有关。目的：观察骨髓间充质干细胞移植对脑出血模型大鼠神经功能恢复及血肿周围轴突生长抑制因子MAG、OMgp表达的影响。方法：全骨髓贴壁法分离培养大鼠骨髓间充质干细胞,使用立体定向纹状体注入胶原酶法制作大鼠脑出血模型。SD大鼠分为假手术组、脑出血模型组及骨髓间充质干细胞干预组,骨髓间充质干细胞干预组于造模后24 h经尾静脉注射1×107的骨髓间充质干细胞悬液,各组于造模后1,3,7,14 d进行神经功能评分,并在各时间点处死大鼠行免疫组织化学法检测MAG、OMgp的表达情况。结果与结论：假手术组术后各个时间点均未见明显神经功能缺损;脑出血模型组神经功能缺损术后1 d时即达高峰,14 d时有进一步的恢复;骨髓间充质干细胞干预组神经功能评分在3,7,14 d各个时间点均较模型组明显降低(P < 0.05)。各个时间点模型组及骨髓间充质干细胞干预组血肿周围神经元及胶质细胞MAG、OMgp的表达均较假手术组明显升高,骨髓间充质干细胞干预组较模型组表达均有降低(P < 0.05)。提示骨髓间充质干细胞移植可明显促进大鼠脑出血后神经功能的恢复,其机制可能与下调血肿周围MAG、OMgp的表达有关。 

Effect of bone marrow-derived mesenchymal stem cell transplantation on the expression of MAG,OMgp in perihematomal tissue in rats with intracerebral hemorrhage

BACKGROUND: Axon regeneration of central nervous system after injury is hard, which is associated with the elevated expression of the axon growth inhibitors: Nogo-A, MAG, OMgp around the lesions. OBJECTIVE: To investigate the effects of intravenous administration of bone marrow-derived mesenchymal stem cells (BMSCs) on the expression of MAG and OMgp in perihematoma tissue in rats with intracerebral hemorrhage (ICH). METHODS: BMSCs were isolated and cultured using the whole bone marrow adherent method. A rat model of ICH was established by stereotaxical injection of collagenase IV into the striatum. Sprague-Dawley (SD) rats were randomly divided into sham-operated group, ICH group (model) and ICH plus BMSCs intervention group (BMSCs group). Rats in the BMSCs group were transfused with BMSCs (1×107/rat) via tail vein at 24 hours after surgery. On days 1, 3, 7, 14 after surgery, neurological function tests were performed among all three groups and animals were sacrificed at the corresponding time points for detecting the expression of MAG, OMgp by immunohistochemical method.RESULTS AND CONCLUSION: No obvious neurological function deficit was observed in sham-operated group on days 1, 3, 7, 14 after surgery. In the model group, the degree of neurological function deficit reached the peak on day 1 after surgery, lasted to day 3, recovery could be observed on day 7, and much more recovery could be seen on day 14. Compared to model group, the BMSCs group had significantly lower mean neurological function rating scores on days 3, 7,14 after surgery (P < 0.05). The mean expression levels of MAG, OMgp in neurons and gliocytes in perihematoma tissue in the model and BMSCs group were both significantly higher than that in the sham-operated group on days1, 3, 7,14 after surgery; meanwhile, the BMSCs group had significantly lower mean expression levels than model group on days 3, 7,14 after surgery (P﹤0.05). Transplantation of BMSCs could significantly promote the neurological function recovery of a rat model of ICH, which might be associated with its downregulation of MAG, OMgp in perihematoma tissue.