Simvastatin与rhG—CSF促进兔颈总动脉球囊损伤后内膜修复的实验研究

目的：观察辛伐他汀及重组人粒细胞集落刺激因子（rhG—CSF）在兔颈总动脉内膜损伤后对血管壁变化及外周血中CD34＋细胞含量的影响。方法：雄性新西兰大白兔48只，随机均分为：单纯损伤组，辛伐他汀组，rhG—CSF组及辛伐他汀和rhG—CSF联合组（简称联合组），建立兔左颈总动脉内膜球囊导管损伤模型，术后给予辛伐他汀（10mg／kg／d经胃灌入）及rhG．CSF（100μg／a皮下注射）干预治疗，每组分别于术前1d、术后7d、14d、21d、28d抽取静脉血2ml，经流式细胞仪检测外周血中CD34＋细胞含量；4周后处死所有动物取损伤段血管，弹力纤维染色，计算内膜厚度、中膜厚度、管腔面积（S）、内膜面积（si）、中膜面积（Sm）TLSi／Sm比值评价血管再狭窄程度。结果：①术前4组之间相比外周血CD34＋细胞含量无明显差异（P〉0．05）；术后7d时各组外周血CD34＋细胞含量最高，后逐渐下降，28d较低，但仍高于术前含量；rhG—CSF组及联合组与对照组相比外周血CD34＋细胞明显增多（P〈O．01，P〈0．01）；术后7d、14天时辛伐他汀组与单纯损伤组相比外周血cD34＋细胞无明显差别（P〉0．05）。术后21d、28天时辛伐他汀组与单纯损伤组相比外周血CD34＋细胞有显著差异（P〈0．05）。②与单纯损伤组相比辛伐他汀组、rhG—CSF组及联合组Si／Sm比值明显减小（P〈0．05）；辛伐他汀组和rhG—CSF组两组间比较无显著差别（P〉0．05）；联合组分别与辛伐他汀组、rhG-CSF组比较血管内膜增生更少，具有显著性（P〈0．01，P〈0．01），结论：本实验研究发现辛伐他汀可促进损伤内膜修复及预防血管再狭窄，长期服用可以增加外周血CD34＋细胞；rhG—CSF可明显增加外周血CD34＋细胞及预防血管在狭窄；辛伐他汀与rhG—CSF联合用药可明显增加外周血CD34＋细胞、加速内皮修复与预防再狭窄，较单一用药具有更好的疗效。

Effects of Simvastatin and rhG-CSF on Endothelium Repair in Balloon-Injured Common Carotid Artery of Rabbits

Objective： To investigate the effects of simvastatin and recombinant human granulocyte colony stimulating factor （rhG-CSF） on the changes in vessel wall and peripheral blood CD34＋content after rabbit carotid artery intima injury. Methods： 48 male New Zealand white rabbits were randomly divided into four groups： single injury group, simvastatin group, rhG-CSF group and combined with simvastatin and rhG-CSF group （combined group）. After injury the left common carotid artery intima balloon-catheter, simvastatin 10 mg·kg·d-1 was pushed into stomach in the simvastatin group, and rhG-CSF 100μg·d-1 was given via subcutaneous injection in rhG-CSF group and combined group, 2ml venous blood was drawed at pre 1 d, after 7d, 14d, 21 d, 28d each group, then CD34 ＋cell levels in peripheral blood were analyzed by flow cytometry, 4 weeks later all animals were killed. The specimens of artery tissue were dyed by elastic fibers staining and HE staining, and the changing of intimal thickness, medial thickness, lumen area （S）, intimal area （Si）, medial area （Sm） and the Si / Sm ratio was evaluated. Results： （1） The preoperative peripheral blood CD34＋cells in 4 groups had no significant difference （P 〉0.05）; After 7d, peripheral blood CD34＋ cells in each group was the highest, then decreased gradually, but peripheral blood CD34＋cells at 28d was still higher than the preoperative levels; The mean density of CD34＋cells at pre ld, after 7d, 14d, 21d, 28d in rhG-CSF group and combination group was higher than the single injury group （P〈0.01, P〈0.01）;There was no discrepancy between the simvastatin group and the single injury group at after7d and afterl4d （P 〉0.05）, while there was significant difference between the simvastatin group and the single injury group at 21d and at 28d.（P〈0.05） （2） Compared with the single injury group, Si/Sm of simvastatin group,rhG-CSF group and combination group significantly reduced （P 〈0.05）; there was no discrepancy between simvastatin group and rhG-CSF group （P 〉 0.05）; Compared with the simvastatin group and rhG-CSF group, combination group had less intimal hyperplasia （P 〈 0.01, P 〈 0.01）. Conclusion： Simvastatin could promote injured intimal repair and prevent restenosis. Long-term use of simvastatin can increase the peripheral blood CD34＋cells; rhG-CSF significantly increases the peripheral blood CD34＋cells and prevents stenosis; Simvastatin and rhG-CSF combination therapy significantly increases the peripheral blood CD34＋cells , accelerates endothelial repair and prevents restenosis, compared with single drug there is better efficacy.