中文摘要：

目的观察辛伐他汀对平滑肌祖细胞（smooth muscle progenitor cell,SPC）和内皮祖细胞（endothelial progenitor cell,EPC）p27蛋白表达的影响,筛选新一代包被洗脱支架药物。方法采用密度梯度离心法从大鼠骨髓获取单个核细胞,将其接种在纤维连接素包被培养板,加入不同浓度辛伐他汀（0.01~10μmol/L）培养24 h后,平滑肌肌动脉蛋白免疫荧光染色鉴定骨髓源性SPC,激光共聚焦显微镜鉴定异硫氰酸荧光素（FITC）结合的植物凝集素（FITC-UEA-Ⅰ）和Di I结合的乙酰化低密度脂蛋白（Di I-ac LDL）双染阳性细胞为正在分化的EPC,Western blot检测p27蛋白的表达。结果辛伐他汀浓度依赖性促进SPC细胞p27表达,0.1μmol/L辛伐他汀即可上调p27表达（n=5,P〈0.01）。与SPC相反,辛伐他汀浓度依赖性抑制EPC细胞p27表达,0.01μmol/L辛伐他汀即可下调p27表达（n=5,P〈0.01）。结论辛伐他汀选择性上调SPC的p27表达,下调EPC的p27表达,局部应用有抑制再狭窄和促进损伤血管再内皮化可能。

英文摘要：

Objectives To investigate different influences of simvastatin on the p27 expressions in rat smooth muscle progenitor cells（SPCs） and endothelial progenitor cells（EPCs）, and to identify compounds that differentially inhibit SPC and EPC proliferation for substantial clinical use. Methods Total mononuclear cells（MNCs） were isolated from rat marrow by Ficoll density gradient centrifugation, and then the cells were planted on fibronectin-coated culture plates. SPCs outgrew from the culture of MNCs in the presence of platelet-derived growth factor-BB and basic fibroblast growth factor, whereas EPCs were obtained in the presence of vascular endothelial growth factor. SPCs were identified as adherent cells positive for α-smooth muscle actin by indirect immunofluorescent staining. EPCs were characterized as adherent cells double positive for Di L-acetylated low density lipoprotein-uptake and lectin binding by direct fluorescent staining. SPCs and EPCs were treated with simvastatin（0.01-10 μmol / L） or vehicle control for 24 h. The expressions of p27 protein were assayed with western blot. Results Simvastatin dose-dependently induced the expression of p27 protein in rat SPCs, which increased in 0.1 μmol / L for 24 h（n=5, P〈0.01）. Contrarily, simvastatin potentially inhibited the expression of p27 protein in rat EPCs in a dose-dependent manner, which decreased in 0.01 μmol / L for 24 h（n=5,P〈0.01）. Conclusions Simvastatin displays a differential effect on SPCs as compared to that on EPCs with regard to the expressions of p27 protein.