辛伐他汀对内皮祖细胞增殖?迁移及凋亡影响的研究
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江苏省卫生厅科技发展基金(H200508)


Simvastatin could improve the proliferation,migration and anti-apoptosis of endothelial progenitor cells
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    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 progenitor cells,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-鄄激酶/蛋白激酶B(PI3K/Akt)信号途径有关-

    Abstract:

    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-蒺 proliferation,migration and anti-apoptosis capability, and the mechanism might be involved in the PI3K/Akt pathway.

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杨乃全,张馥敏,胡政力,张定国,马文珠.辛伐他汀对内皮祖细胞增殖?迁移及凋亡影响的研究[J].南京医科大学学报(自然科学版),2007,(9):952-955

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  • 收稿日期:2007-03-19
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