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目的:探讨不同剂量的粒细胞集落刺激因子(G-CSF)对兔股动脉粥样斑块的作用。方法:24只新西兰兔以高脂饮食和股动脉球囊扩张建立动脉粥样硬化模型,随机分为空白对照组(8只),小剂量G-CSF干预组(8只)和大剂量G-CSF干预组(8只)。空白对照组不给药;小剂量G-CSF组隔天皮下注射G-CSF0.8 mL(4μg.kg-1.d-1),共7针;大剂量G-CSF组隔天皮下注射G-CSF 2.4 mL(12μg.kg-1.d-1),共7针。造模前、给药结束后及给药结束3周后分别测定血常规。给药结束3周后,取股动脉粥样斑块进行HE染色和CD34免疫组化染色,测定斑块内泡沫细胞比例和新生血管计数。结果:各组在G-CSF干预前后的白细胞计数、中性粒细胞计数、血红蛋白量均无明显差别。大剂量G-CSF组在给药结束3周后的中性粒细胞比例明显低于基线值(P<0.01)。小剂量G-CSF组在给药结束后、大剂量G-CSF组在给药结束3周后的血小板计数均高于用药前水平(P<0.05,P<0.01)。小剂量G-CSF组的动脉斑块局部新生血管计数显著低于对照组(P<0.05),大剂量G-CSF组也有降低趋势,但未达到统计学差异。G-CSF干预组的斑块内泡沫细胞面积比例与对照组比较没有统计学差异。结论:小剂量G-CSF能减少粥样斑块局部的新生血管数量,有利于斑块稳定,大剂量G-CSF则没有这种作用。2种剂量的G-CSF对于粥样斑块的净效应呈中性,可能和外周血炎症细胞和血小板的动员有关。
Objective: To investigate the effect of different doses of granulocyte-colony stimulating factor (G-CSF) on atherosclerotic plaque in rabbits. Methods: A total of 24 New Zealand rabbits were randomly divided into blank control group (n = 8), low dose G-CSF intervention group (n = 8) and high dose G- CSF intervention group (8). The blank control group was given no drug. Small dose of G-CSF group was given subcutaneous injection of G-CSF 0.8 mL (4 μg.kg-1.d-1) -CSF 2.4 mL (12 μg.kg-1.d-1) for a total of 7 needles. Before modeling, after the end of administration and 3 weeks after the end of administration were determined blood routine. Three weeks after the administration, HE staining and CD34 immunohistochemical staining of atherosclerotic plaques were performed to determine the proportion of foam cells in the plaque and neovascular count. Results: There was no significant difference in the number of leucocyte, neutrophil count and hemoglobin before and after G-CSF intervention in each group. Neutrophils in the high-dose G-CSF group were significantly lower than the baseline value 3 weeks after the end of administration (P <0.01). In the low-dose G-CSF group, the platelet count of the high-dose G-CSF group was higher than that of the pre-drug group (P <0.05, P <0.01) after 3 weeks of administration. The small number of G-CSF group of arterial plaque local neovascular count was significantly lower than the control group (P <0.05), high-dose G-CSF group also decreased, but did not reach statistical significance. G-CSF intervention group plaque foam cell area ratio compared with the control group no statistically significant difference. CONCLUSIONS: G-CSF at a low dose can reduce the number of local neovascularization in atherosclerotic plaque and stabilize the plaque. High-dose G-CSF does not have this effect. The net effect of 2 doses of G-CSF on atherosclerotic plaques was neutral and may be related to the mobilization of inflammatory cells and platelets in peripheral blood.