Mei Que-lin, Yang Jian-yong, Li Yan-hao, Chen Zai-zhong, Yu Hong-jian, Liu Peng-cheng
Department of Radiology, Peking University Shenzhen Hospital, Shenzhen Medical Centre, Peking University-Hong Kong University of Sciences and Technology, Shenzhen, Guangdong 518036, China.
Chin Med J (Engl). 2008 Jan 20;121(2):143-6.
Endothelial progenitor cells (EPCs) derived from bone marrow may differentiate into endothelial cells and participate in endothelial repair. These cells can be mobilized into peripheral blood by cytokines, including granulocyte colony-stimulating factor (G-CSF). In the present study, we investigated the effects of G-CSF on neointimal formation and restenosis in a canine model of arterial balloon injury.
Sixteen male beagle dogs were injected subcutaneously with 20 microg x kg(-1) x d(-1) recombinant human G-CSF (n = 8) or normal saline (n = 8) for 1 week. On the fifth day of treatment, the dogs underwent renal arterial angioplasty. At 8 weeks after arterial balloon injury, angiographic observations were made and injured arteries were processed for morphometric analysis of neointimal formation.
Peripheral white blood cell counts were increased by 3.34-fold compared to baseline on the fifth day of administration of G-CSF. Angiographies revealed that one stenosis had occurred among the eight injured renal arteries from dogs treated with G-CSF, whereas all injured renal arteries from dogs treated with normal saline remained patent. The mean extent of stenosis among injured arteries was 18.3% +/- 17.9% in the G-CSF treated group compared to 12.5% +/- 7.6% in the saline treated control group (P = 0.10). G-CSF treatment slightly increased neointimal thickness (0.42 +/- 0.15 mm vs 0.25 +/- 0.06 mm, P = 0.08) with an intima to media ratio of 0.83 +/- 0.49 vs 0.54 +/- 0.18 (P = 0.11).
G-CSF treatment does not attenuate neointimal hyperplasia and restenosis formation in a canine model of renal arterial injury, suggesting that the therapeutic strategy for preventing restenosis by stem cell mobilization should be investigated further.
源自骨髓的内皮祖细胞（EPCs）可分化为内皮细胞并参与内皮修复。这些细胞可被包括粒细胞集落刺激因子（G-CSF）在内的细胞因子动员至外周血中。在本研究中，我们在犬动脉球囊损伤模型中研究了G-CSF对新生内膜形成和再狭窄的影响。
16只雄性比格犬皮下注射20μg·kg⁻¹·d⁻¹重组人G-CSF（n = 8）或生理盐水（n = 8），持续1周。在治疗的第5天，对犬进行肾动脉血管成形术。动脉球囊损伤8周后，进行血管造影观察，并对损伤动脉进行处理以进行新生内膜形成的形态计量分析。
在给予G-CSF的第5天，外周白细胞计数较基线增加了3.34倍。血管造影显示，接受G-CSF治疗的犬的8条损伤肾动脉中有1条发生狭窄，而接受生理盐水治疗的犬的所有损伤肾动脉均保持通畅。G-CSF治疗组损伤动脉的平均狭窄程度为18.3%±17.9%，而生理盐水治疗对照组为12.5%±7.6%（P = 0.10）。G-CSF治疗使新生内膜厚度略有增加（0.42±0.15mm对0.25±0.06mm，P = 0.08），内膜与中膜比值为0.83±0.49对0.54±0.18（P = 0.11）。
在犬肾动脉损伤模型中，G-CSF治疗并未减轻新生内膜增生和再狭窄形成，提示通过干细胞动员预防再狭窄的治疗策略应进一步研究。
