【摘要】 背景:骨髓间充质干细胞虽然能促进神经再生,但因治疗方式局限,并未取得较好的疗效。应用单纯的骨髓间充质干细胞移植治疗脑损伤还远不能达到治疗和改善病情的目的。目的:探讨成纤维细胞生长因子修饰的骨髓间充质干细胞对颅脑损伤后功能恢复及胶质纤维酸性蛋白表达的影响。方法:采用液压冲击法建立SD大鼠颅脑创伤模型,建模后随机分为对照组(颅脑损伤组)、骨髓间充质干细胞组及成纤维细胞生长因子-骨髓间充质干细胞组。体外分离、培养骨髓间充质干细胞,利用腺病毒载体介导成纤维细胞生长因子基因转染入骨髓间充质干细胞。采用Western-Blot法检测成纤维细胞生长因子基因转染及胶质纤维酸性蛋白的表达情况;应用免疫组化检测Brd U标记的骨髓间充质干细胞在脑内的分布及数量;利用Longa评分法于移植后1 d、3 d、1周、2周对大鼠进行神经功能学评分;TUNEL法检测脑组织细胞的凋亡情况。结果与结论:Western-Blot结果显示,成纤维细胞生长因子基因成功转入腺病毒载体,并且能够在骨髓间充质干细胞中表达,且胶质纤维酸性蛋白在成纤维细胞生长因子-骨髓间充质干细胞组的表达明显高于其他两组(P<0.05)。BrdU标记的骨髓间充质干细胞在成纤维细胞生长因子-骨髓间充质干细胞组脑组织中的表达明显高于其他两组(P<0.05)。移植后2周,成纤维细胞生长因子-骨髓间充质干细胞组大鼠的神经功能缺损Longa评分明显低于其他两组(P<0.05)。TUNEL检测到的凋亡细胞数在成纤维细胞生长因子-骨髓间充质干细胞组明显少于其他两组(P<0.05)。提示成纤维细胞生长因子修饰的骨髓间充质干细胞移植能够减轻颅脑损伤模型大鼠的神经功能损伤程度,促进神经功能恢复,效果优于骨髓间充质干细胞单独移植治疗。更多还原

【Abstract】 BACKGROUND: Bone marrow mesenchymal stem cells(BMSCs) can promote nerve regeneration, but there are no better results because of the limitations of treatment methods. BMSC transplantation alone is not enough to achieve desired therapeutic effects.OBJECTIVE: To investigate the effect of fibroblast growth factor(FGF)-modified BMSC transplantation on functional recovery and expression of glial fibrillary acidic protein after traumatic brain injury. METHODS: Animal models of traumatic brain injury were established in Sprague-Dawley rats using hydraulic shock method, and then randomized into control group(traumatic brain injury group), BMSC group and FGF-BMSC group(FGF-modified BMSC group). After isolation and culture, BMSCs were modified by adenovirusvector-mediated FGF gene. Western blot assay was used to detect transfection efficiency and glial fibrillary acidic protein expression; immunohistochemical detection was used to detect distribution and number of Brd U positive cells in the brain; Longa score was used to evaluate the neurologic function of rats at 1, 3 days, 1, 2 weeks after transplantation; TUNEL assay was used to detect cell apoptosis in the brain. RESULTS AND CONCLUSION: Western blot results showed that FGF gene was successfully transferred to the adenovirus vector, and capable of expressing in BMSCs; moreover, the glial fibrillary acidic protein expression of FGF-BMSC group was significantly higher than that in the other two groups(P < 0.05). The number of Brd U positive cells in the brain was significantly higher in the FGF-BMSC group than the other two groups(P < 0.05). Two weeks after transplantation, the Longa scores in the FGF-BMSC group were significantly lower than those in the other two groups(P < 0.05). TUNEL results showed that the number of apoptotic cells in the FGF-BMSC group was significantly lower than that in the other two groups(P < 0.05). These findings indicate that FGF-modified BMSCs transplantation is able to improve neurological damage after traumatic brain injury and promote neurological recovery, which is better than BMSC transplantation alone.更多还原