重组人粒细胞集落刺激因子对大鼠海马慢性持续性低血流灌注后的修复作用

目的通过对大鼠海马的持续性低血流灌注，观察大鼠海马CA1区锥体细胞、胶质细胞对粒细胞集落刺激因子（G-CSF）动员骨髓干细胞向中枢神经系统迁移的反应，探讨G-CSF对大鼠持续性低血流灌注状态下海马CA1区的病理学修复机制。方法建立大鼠持续性低血流灌注模型（2VO术），术后20周给予重组人粒细胞集落刺激因子（rhG-CSF）动员骨髓干细胞，应用免疫组织化学SP技术和图像分析技术，分析海马CA1区CD34阳性细胞、锥体细胞的数量及其分布状况、以及胶质原纤维酸性蛋白（GFAP）阳性细胞的数量和胞质突起的长度变化。结果连续给予rhG-CSF后大鼠海马CA1区可见CD34阳性细胞存在，提示其动员了骨髓干细胞向中枢神经系统迁移。相对于对照组（生理盐水治疗组），在持续性大脑低灌流状态下，大鼠海马CA1区锥体细胞数量明显增多，GFAP阳性细胞数量明显增多、其胞质突起分支增加、长度明显缩短。结论大鼠海马经持续性低血流灌注后，rhG-CSF可通过动员骨髓细胞向中枢神经系统的迁移，促进海马区锥体细胞、胶质细胞的增生或（和）激活，增强修复能力，为慢性持续性低血流灌注脑损伤的治疗提供了新的思路。

The Repair Effect of Hippocampus after rhG-CSF Treatment in Chronic Continuously Cerebral Hypoperfusion in Adult Rats

Objective To investigate the repair mechanism of hippocampus after granulocyte colony-stimulating factor(G-CSF) intervention in chronic hypoperfusion,through observing the response of hippocampal CA1 pyramidal neurons and astrocytes after G-CSF mobilizing bone marrow stem cell transplantation into the central nervous system in chronic continuously cerebral hypoperfusion model of adult rats.Methods Chronic continuously cerebral hypoperfusion model of rats was established by permanent occlusion of bilateral common carotid arteries(2VO).Twenty weeks later,recombinant human(rh) G-CSF was administered to mobilize bone marrow stem cells.The number of the CD34 positive cells,pyramidal neurons and glial fibrillary acidic protein(GFAP) positive cells,and the length of the processes of GFAP positive cells in hippocampus CA1 were measured by SP immunohistochemical technique and image analysis technique.Results After continuous administration of rhG-CSF,CD34 positive cells in hippocampus CA1 were seen in rats,suggesting rhG-CSF could mobilize bone marrow stem cells to migrate into the central nervous system.As compared with control group,the number of the CD34 positive cells,pyramidal cells and GFAP positive cells in the hippocampal CA1 was increased obviously,and the kytoplasm ecphyma of GFAP positive cells were obviously shortened,and the branches of the processes were increased in chronic continuously cerebral hypoperfusion of adult rats.Conclusion After chronic continuously cerebral hypoperfusion,rhG-CSF can mobilize bone marrow stem cells to migrate into the central nervous system,and then stimulate pyramidal neurons and astrocytes of the hippocampal CA1,which can enhance the ability of repair.