动员自体骨髓干细胞对大鼠脑缺血/再灌注损伤及细胞凋亡的影响  

Experimental study on the effect of mobilizing autologous bone marrow stem cells on focal cerebral ischemia/reperfusion injury and neuron apoptosis in rat

作　　者：刘雪平[1] 张子强[1] 高顺宗[1] 迟翔宇[1] 朱竹先[2] 

机构地区：[1]山东大学山东省立医院老年病科,济南250021 [2]山东大学山东千佛山医院

出　　处：《中国神经科学杂志》2004年第3期226-230,共5页

摘　　要：目的　 探讨应用G CSF动员自体骨髓干细胞对大鼠脑缺血 /再灌注损伤及细胞凋亡的影响。 方法　 应用线栓法制备大鼠局灶性大脑中动脉栓塞 /再灌注 (MCAO/R)模型 ,应用粒细胞集落刺激因子 (G GSF)刺激自体骨髓干细胞分裂增殖 ,并用 5 溴脱氧尿核苷 (Brdu)标记。观察大鼠神经病学评分 ,HE染色和免疫组化检测脑缺血区病理改变及CD34和Brdu阳性细胞 ,原位末端标记法 (TUNEL法 )观察细胞凋亡。 结果　 模型动员组大鼠脑缺血 /再灌注后 2 4h ,大量炎症细胞浸润。再灌注后 4 8h ,缺血区可见CD34和Brdu阳性细胞 ;72h后CD34阳性细胞消失 ,而Brdu阳性细胞持续存在 ;模型未动员组缺血区无CD34和很少Brdu阳性细胞表达。 4 8h缺血区新生毛细血管密度明显高于对照组。再灌注后 2 4h细胞凋亡显著 ,1周时达高峰 ;与模型非动员组比较 ,模型动员组 4 8h后细胞凋亡改善明显。结论　自体骨髓干细胞经G CSF动员后可向大鼠脑缺血区趋化并可分化为神经元前体细胞 ,显著促进脑缺血区血管再生 ,降低脑神经功能评分 ,降低细胞凋亡率。Objective To investigate the effect of mobilizing bone marrow stem cells on focal middle cerebral artery occlusion/reperfusion (MCAO/R)and the neuron apoptosis. Methods MCAO/R model was induced by using the filament occlusion method. Bone marrow stem cells were mobilized by granulocyte colony-stimulating factor (G-CSF). The neurological scale were evaluated after focal cerebral ischemia in rats, HE stain and immunohistochemistry were used to detect the pathologic change and the infiltration cells with positive expression of CD34 and 5-bromodeoxyuridine (Brdu) in the regions of ischemia, the change of cell apoptosis rate was analysed by the TUNEL method. Results In the G-CSF mobilizing MCAO/R group, after the focal cerebral ischemia/reperfusion injury, large number of infiltrative lymphocytes and some myocytes were found at 24 h, large number of cells with positive expression of CD34 were found at 48 h and disappeared at 72 h; meanwhile, Brdu positive cells existed even over one week. In contrast, there were no cells with potisive expression of CD34 and less Brdu cells in the groups without moblization. At 48 h after cerebral ischemia/reperfusion, there was higher capillary density in the G-CSF mobilizing MCAO/R group than those in the non-G-CSF mobilizing MCAO/R group. A large number of apoptosis cells appeared and reached a peak one week after the cerebral ischemia/reperfusion injury, but they were lower in the mobilizing MCAO/R group than in the non-G-CSF mobilizing MCAO/R groups 48 h after the injury. Conclusion Autologous bone marrow stem cells mobilized by G-CSF can migrate into the region of ischemia and differentiate into neuron-like cells to enhance neovascularization regenerating, improve neurological deficit scores and reduce the rate of neuron apoptosis.

关 键 词：动员自体骨髓干细胞 脑缺血 再灌注损伤 细胞凋亡 

分 类 号：R361[医药卫生—病理学]