IGF-1对缺血性脑损伤大鼠脑内神经发生的影响

目的:建立大鼠单侧局灶脑缺血模型,观察胰岛素样生长因子-1(IGF-1)对局灶脑缺血后的鼠脑神经发生及增殖后细胞生存的影响.方法:用健康雄性SD大鼠建立大脑中动脉阻塞(MCAO)模型,随机分成假手术组,缺血对照组和IGF-1治疗组.各组再按不同的治疗时间分为7d、14d、28d、42d组.免疫组化法观察BrdU、PSA-NCAM的变化,免疫双标法观察BrdU/PSA-NCAM、BrdU/MAP2和BrdU/GFAP的共同表达变化.结果:BrdU标记细胞和PSA-NCAM标记细胞计数均在缺血后第7d最多,分别是缺血对照组的4.0倍和1.8倍,是假手术组的9.9倍和5.4倍.BrdU和PSA-NCAM双标细胞在缺血发生后双侧SVZ和DG区可以检测到,于第7d计数最多,之后逐渐降低;而BrdU和MAP2以及BrdU和GFAP双标细胞却从第14d开始逐渐增多,直到第42d.随着BrdU/PSA-NCAM双标阳性表达的逐渐降低,BrdU/MAP2双标阳性表达逐渐增高,呈现此消彼涨的变化.结论:IGF-1侧脑室注射后,在早期(7d内)诱导了缺血性脑损伤后神经细胞的增殖;在中期(7d-14d)诱导了新生细胞的迁移;在后期(14d后)伴随着迁移的进行新生细胞逐渐发生了分化.

Effects of IGF-1 on Neurogenesis after Focal Cerebral Ischemia in Rats

Objective:To examine the effect of Insulin-like growth factor(IGF-1)on neurogenesis after focal cerebral ischemia in rats.Methods:Male SD rats were subjected to cerebral middle artery occlusion operation(MCAO),and then they were randomly divid- ed into three groups:sham-operation group,ischemia control group and IGF-1 group after successful modeling.Every 6 rats(random se- lected)in the three groups were sacrificed at 7d,14d,28d and 42d after MCAO,respectively.BrdU-labeled cells,PSA-NCAM-labeled cells,BrdU/PSA-NCAM-Iabeled cells expression,BrdU/MAP2-1abeled cells expression and BrdU/GFAP-labeled cells expression were identified by immunohistochemistry staining and double immunohistochemistry staining.Result:BrdU-ladeled cells and PSA-NCAM-la- beled cells increased approximately by 4.0-fold and 1.8-fold compared with the ischemia control groups,9.9-fold and 5.4-fold compared with sham-operated groups,respectively.Both BrdU-ladeled cells and PSA-NCAM-labeled cells reached the largest number at 7d after MCAO.BrdU/PSA-NCAM labeled cells expression were detected the largest cell number both in the SVZ and DG at 7d after ischemia and gradually decrease after that day.But BrdU/MAP_2-1abeled cells and BrdU/GFAP-labeled cells gradually increased from 14d after is- chemia.Conclusion:IGF-1 induced cells proliferation before 7d and migration of regenerated cells at 7d-14d after MCAO operation in rats;differentiation of regenerated cells occurred while migration was proceeding from 14d after MCAO.