【摘要】 目的观察腺病毒介导的脑源性神经营养因子(brain-derived neurotrophic factor,BDNF)对大鼠脑出血后内源性神经干细胞(nerve stem cells,NSCs)分化的影响。方法建立大鼠自体血脑出血(intracerebral hemorrhage,ICH)模型,将126只大鼠分为生理盐水组(NS组)、单纯腺病毒载体干预组(Ad组)和BDNF干预组(Ad-BDNF组),每组42只。模型制作后分别将NS、Ad、Ad-BDNF注射到出血侧血肿周围。BrdU标记内源性NSCs,于1、3、7、14、2l、28 d进行神经缺失功能评分。免疫荧光单标法观察3组血肿周围GAP-43的表达。免疫荧光双标法观察脑出血大鼠28 d时NSCs的分化。结果 Ad-BDNF组在第7、14、21、28天神经缺失功能评分优于NS组和Ad组(P<0.01)。GAP-43在脑出血出血同侧3 d时表达明显增加,7 d达高峰,以后逐渐减少。Ad-BDNF组在第3、7、14、21、28天的GAP-43表达明显增加,与NS、Ad组比较差异有统计学意义(P<0.05)。28 d时Ad-BDNF组BrdU/NeuN双标阳性细胞率为(39.69±17.45)%、BrdU/GFAP双标阳性细胞率为(63.53±21.68)%,与NS组、Ad组比较明显增加(P<0.05)。结论腺病毒介导的BDNF可促进脑出血后内源性NSCs的分化和轴突再生,有利于神经功能的恢复。更多还原

【Abstract】 Objective To observe the effects of adenovirus-mediated brain-derived neurotrophic factor(Ad-BDNF) on differentiation of endogenetic nerve stem cells(NSCs) after intracerebral hemorrhage(ICH).Methods A rat ICH model was established by right intrastriatal administration of autologous whole blood.One hundred and twenty-six rats were divided into normal saline(NS) group,adenovirus interference group(Ad group) and Ad-BDNF interference group,42 rats in each group.NS,Ad and Ad-BDNF were injected into the perihematomal area of rats,respectively.Expression of GAP-43 and differentiation of NSCs were observed with single immunofluorescence labeling method and double immunofluorescence labeling method,respectively in 4 weeks after establishment of ICH model.Results The score of NSC function was higher in Ad-BDNF interference group than in NS and Ad interference groups in 7,14,21 and 28 d after establishment of ICH model(P<0.01) with no significant difference between NS and Ad interference group(P>0.05).The expression level of GAP-43 was significantly higher in the perihematomal area of rats in 3 d after establishment of ICH model,reached its peak in 7 d after establishment of ICH model,and then gradually decreased,but no significant difference was found between NS and Ad interference groups(P>0.05).The expression level of GAP-43 was significantly higher in Ad-BDNF interference group than in NS group and Ad interference group in 3,7,14,21 and 28 d after establishment of ICH model(P<0.05),but no significant difference was observed between NS and Ad interference groups(P>0.05).The differentiation rates of endogenetic NSCs [BrdU/NeuN=(39.69±17.45)% and BrdU/GFAP=(63.53±21.68)%] were significantly higher in Ad-BDNF interference group than in NS and Ad interference groups in 28 d after establishment of ICH model(P<0.05).Conclusion Ad-BDNF can increase the differentiation of endogenetic NSC and improve the recovery of nerve function after ICH.更多还原