自体骨髓干细胞动员治疗脑创伤的实验研究

目的探讨自体骨髓干细胞（BMSCs）动员治疗脑创伤（TBI）的疗效、机制及治疗时机。方法SD大鼠参照Feeney方法制作TBI模型，随机分为对照组（A组）、自体BMSCs动员TBI急性期治疗组（B组）和亚急性期治疗组（C组）。采用神经功能缺损评分（NSS）和电迷宫试验检测大鼠脑功能，脑组织病理和免疫组织化学检测5-溴脱氧尿嘧啶核苷（Brdu）、胶质纤维酸性蛋白（GFAP）、脑源性神经营养因子（BDNF）、Nestin和Ⅷ因子抗原，TUNEL检测细胞凋亡。结果B、C两组大鼠NSS评分、电迷宫试验错误反应次数均较A组显著降低（P〈0．05）。B、C组创伤早期脑组织水肿和坏死面积及晚期神经瘢痕形成均少于A组；B、C组BrdU＋GFAP荧光双标阳性、BDNF表达和微血管计数均较A组显著增多（P〈0．05），B组较C组增多但无统计学意义（P〉0．05）；B组Nestin表达显著高于A、C组（P〈0．05），而细胞凋亡数较A、C组显著减少（P〈0．05）。结论动员的自体BMSCs向脑创伤组织区聚集、增殖、分化，分泌神经营养因子、促进血管生成、减少细胞凋亡，促进神经再生与TBI修复，改善大鼠脑功能；自体BMSCs动员治疗急性期和亚急性期TBI均有效，急性期疗效优于亚急性期。

The experimental study on autologous bone marrow stem cells mobilization of traumatic brain injury

Objective To observe the effects and mechanisms of treating traumatic brain injury （TBI） in rats by mobilization transplantation of autologous bone marrow stem cells （BMSCs） as well as the best time for the treatment. Methods Male Sprague-Dawley rats were chosen, after being given TBI model by using Dermis M. Feeney method, randomly divided into the TBI group （ group A ） , the mobilized transplanted group treating with antologous BMSCs at the acute phase of TBI （ group B）, and that treating at the subacute phase（ group C）. The function of the nervous system in rats was detected by using neurological severity scores （NSS） and electric maze tests. Histopathology observation, immunohistochemistry detects BrdU, GFAP, BDNF, Nestin and Factor V~ antigen. Terminal deoxynucleotidyl Transferase Biotin-dUTP Nick End Labeling （TUNEL） detects apoptosis. Results The NSS scores and error reaction times in Y-electric maze test of group B and C were significantly lower than those of group A （ P 〈 0. 05 ）. The edema and necrosis area in early and neural scar formation of group B and C were better than that of group A ; Compared with group A the number of BrdU ＋ GFAP positive cells, expression of BDNF.and angiogenesis was much bigger than that of group A （P 〈 0.05 ）, while compared between group B and C the difference had no statistical significance though the count of the former is more than the latter. The Nestin positive cells of group B were significantly more than that of group A and C （ P 〈 0. 05）, while the apoptotic ceils of group B are less than that of the other two groups. Conclusions The autologous BMSCs worked by gathering into damage region, prolifering, differentiating, secreting neurotrophic factors, promoting angiogenesis, reducing apoptosis to promote nerve regeneration and TBI rehabilitation and improve brain function in rats. Mobilization transplantation of autologous BMSCs might be an effective method for both acute phase TBI and subacute phase TB1, and the efficacy of the former is better than the latter.