目的:探讨移植脑源性神经营养因子(BDNF)体外诱导的骨髓间充质干细胞(BMSCs)治疗大鼠脑缺血模型的作用。方法:采用线栓法制作大脑中动脉闭塞(MCAO)模型,移植前6hBDNF体外诱导BMSCs分化为神经元样细胞。1×10^7经BD—NF体外诱导的或未诱导的BMSCs经鼠尾静脉移植。移植后第2,7,14,21,28天行大鼠神经缺失功能的测定,免疫组织化学染色和蛋白质印迹法检测神经细胞特异性烯醇化酶(NSE)的蛋白表达。结果:移植后第14天和第21天,BDNF-BMSCs移植组与BMSCs移植组较未移植组神经缺失功能评分明显好转,移植后第21天,BDNF-BMSCs移植组的神经功能缺失评分较BMSCs移植组高(P〈0.05)。BMSCs移植对运动功能的改善作用更明显,而在观察时间内BMSCs对感觉缺失功能恢复较慢。免疫组织化学染色和蛋白质印迹法显示移植第7天,NSE在BDNF-BMSCs移植组中的表达明显较其他组增强(P〈0.05)。结论:移植BDNF体外诱导的BMSCs能增强BMSCs改善缺血性大鼠神经缺失功能及NSE的蛋白表达。BDNF和BMSCs可能通过上调NSE表达改善缺血性大鼠神经缺失功能。
Objective: To investigate the effect of bone mesenchymal stem cells (BMSCs) induced by brain- derived neurotrophic factor (BDNF) on neurological deficits in the rats with stroke. Methods: The BMSCs were harvested from 6-week-old male Sprague-Dawley rats. Adult male Sprague-Dawley rats weighing 250-280 g with transient middle cerebral artery occlusion were administered with 1-107 BMSCs or BMSCs induced by BDNF in 1 mL phosphate-buffered saline via tail vein at 48 h after stroke. All animals underwent neurological function test on days 2, 7, 14, 21 and 28. Immunohistochemical staining and Western blotting for neuron specific enolase (NSE) were applied. Results: The rats treated with BDNF-BMSCs and BMSCs showed significant improvement of neurological deficits compared to vehicle controls on days 21 and 28 ( P (0.05), especially, BDNF-BMSCs exhibited remarkable functional recovery compared to BMSCs transplantation alone on day 21 ( P (0.05). Both BDNF-BMSCs and BMSCs, especially BDNF-BMSCs, upregulated the NSE protein levels. Conclusion: BDNF and BMSCs might contribute to the functional improvement of neurological deficits partly via upregalating NSE expression level.