辛伐他汀对冠心病患者内皮祖细胞增殖的影响及其机制初步探讨  

Effect and mechanism of simvastatin on the proliferation of endothelial progenitor cells

作　　者：徐全胜[1] 张家明[2] 李宾公[2] 王朝晖[2] 王祥[2] 

机构地区：[1]武汉市第一医院心内科,湖北武汉430030 [2]华中科技大学同济医学院附属协和医院心内科

出　　处：《心血管康复医学杂志》2007年第3期271-274,共4页Chinese Journal of Cardiovascular Rehabilitation Medicine

摘　　要：目的:观察辛伐他汀对冠心病患者外周血内皮祖细胞(EPCs)增殖的影响并初步探讨其机制。方法:冠心病患者28例,随机分为辛伐他汀组和对照组,前者给予辛伐他汀40mg/d口服,治疗前及治疗后2、4周抽取外周血,采用密度梯度离心法获取单个核细胞,培养7d后对贴壁的细胞进行分析。以激光共聚焦显微镜鉴定为FITC标记的荆豆凝集素Ⅰ和Dil(一种亲脂性碳化青荧光染料)标记的乙酰化低密度脂蛋白双染色阳性细胞为EPCs。计数法比较二组EPCs数目,并对病人血浆低密度脂蛋白-胆固醇(LDL-C)水平和EPCs数进行相关分析。另取10例冠心病患者血培养EPCs,加入辛伐他汀、PI3K/Akt信号转导通路抑制剂Wortmannin后观察对其增殖的影响。结果:辛伐他汀组病人治疗后2周、4周外周血中EPCs明显上升(P<0.01),其变化与LDL-C变化无相关性(P>0.05),体外实验辛伐他汀+Wortmannin组的血EPC数目较辛伐他汀组明显下降(P<0.01)。结论:辛伐他汀能刺激EPCs的增殖,这种作用能被Wortmannin阻断。故辛伐他汀作用可能与激活PI3K/Akt信号转导通路有关。Objective： To investigate the effect of simvastatin on the proliferation of endothelial progentior cells （EPCs） and possible mechanism. Methods.. The 28 patients with coronary heart disease （CHD） were divided into two groups： simvastatin group and control group. The former were treated with 40 mg of simvastatin per day for 4 weeks. Before and 2 weeks or 4 weeks after the statin therapy, mononuelear cells were isolated from blood of patients by density gradient eentrifugation. Adherence cells were harvested after 7 days culture. EPCs were characterized as adherent cells with double positive for Dil-aeLDL-uptake and ulex europaeus agglutinin （UEA） binding by direct fluorescent staining under a laser scanning eonfoeal microscope. EPCs were counted and analyzed. In addition, Liner correlation was used to analyze the relationship between the numbers of EPCs and LDL-C levels. EPCs harvested from other 10 patients blood were incubated with or without simvastatin and Wortmannin, a specific inhibitor of PI3K. Then the proliferation of EPCs was investigated. Results： The number of EPCs significantly increased in subjects with simvastatin in 2 or 4 weeks （P〈0. 01）. In addition, the numbers of EPCs did not correlated with LDL-C levels before or after treatment. （P〉0.05）. The number of EPCs decreased （p〈0.01） after to add wortmannin in vitro experiment in simvastatin group. Conclusion： Simvastatin can stimulate the proliferation of EPCs and this effect may be inhibited by wortmannin.

关 键 词：辛伐他汀 干细胞 PI3K/AKT 

分 类 号：R544.1[医药卫生—心血管疾病]