辛伐他汀对内皮祖细胞增殖、迁移及凋亡影响的研究  

Simvastatin could improve the proliferation,migration and anti-apoptosis of endothelial progenitor cells

作　　者：杨乃全[1] 张馥敏[1] 胡政力[1] 张定国[1] 马文珠[1] 

机构地区：[1]南京医科大学第一附属医院心内科,江苏南京210029

出　　处：《南京医科大学学报（自然科学版）》2007年第9期952-955,共4页Journal of Nanjing Medical University(Natural Sciences)

基　　金：江苏省卫生厅科技发展项目(H200508)

摘　　要：目的:细胞水平观察不同浓度辛伐他汀对内皮祖细胞(endothelial progenitorcells,EPCs)功能的影响。方法:采用密度梯度离心法从人外周血获取单个核细胞,将其接种在人纤维连接蛋白包被培养板上,培养7天后,收集贴壁细胞,通过激光共聚焦显微镜鉴定,FITC-UEA-I和DiI-acLDL双染色阳性细胞为正在分化EPCs。以不同浓度辛伐他汀(分别为0.0001、0.0010、0.0100、0.1000、1.0000 μmol/L)或PI3K阻断剂(LY294002)+0.01 μmol/L辛伐他汀和EPCs培养。分别采用MTT比色法、改良的Boyden小室和碘化丙啶(PI)标记观察辛伐他汀对EPCs的增殖、迁移和凋亡影响。结果:辛伐他汀显著提高了外周血EPCs的迁移能力、增殖能力与抗凋亡能力(P<0.05)。辛伐他汀浓度在0.01 μmol/L时对EPCs功能影响达到最大。随着药物浓度的继续增大,EPCs的上述功能反呈下降趋势,但0.1 μmol/L组仍高于对照组。辛伐他汀对EPCs的功能影响能被LY294002阻断。结论:辛伐他汀能增加EPCs的增殖、迁移、抗凋亡功能,其机制可能与磷酸酰肌醇-3-激酶/蛋白激酶B(PI3K/Akt)信号途径有关。Objective：To investigate whether simvastatin of different concentrations have influences on the functions of EPCs in vitro. Methods：Total mononuclear cells（MNCs） were isolated from human peripheral blood by Ficoll density gradient centrifugation,and then the cells were plated on fibronectin-coated culture dishes. After 7 days cultured,attached cells were isolated and assessed with a laser scanning confocal microscope. Differentiating EPCs were characterized as adherent cells double positive for DiLDL-uptake and lectin binding. EPCs were treated with simvastatin of different concentrations（0.0001,0.0010,0.0100,0.1000,1.0000 μmol/L）,or LY294002（PI3K inhibitor） plus simvastatins（0.01 μmol/L ）. The influences of simvastatin on EPCs＇ proliferation,migration and apoptosis were assayed with MTT assay,modified Boyden chamber assay and FACS assay, respectively. Results：Simvastatin strikingly improved the ability in proliferating,migrating and anti-apoptosis of EPCs isolated from human peripheral blood（P 〈 0.05）. Simvastatin at 0.01 μmol/L concentration reached the maximum effects on EPCs,while the concentration of simvastatin was further increased more than 0.01 μmol/L,the improvement effects showed a tendency to decline,but the effects at 0.1 μmol/L concentration were still greater than those in control group. And the influences of simvastatin on these functions of EPCs could be blocked by LY294002. Conclusion：The present study established that simvastatin could improve EPCs＇ proliferation,migration and anti-apoptosis capability, and the mechanism might be involved in the PI3K/Akt pathway.

关 键 词：他汀类药物 内皮祖细胞 增殖 迁移 凋亡 

分 类 号：R541.4[医药卫生—心血管疾病]