甲羟孕酮对内皮祖细胞增殖、迁移和凋亡的影响

Effects of Medroxyprogesterone Acetate on Endothelial Progenitor Cell

探讨不同浓度醋酸甲羟孕酮(MPA)对内皮祖细胞(EPCs)增殖、凋亡以及迁移的影响,以期了解MPA抗血管生成的机制。体外分离培养犬骨髓EPCs,并用免疫细胞化学方法检测孕激素受体(PR)的表达;以不同浓度MPA作用于EPCs,MTT法绘制生长曲线,并计算抑制率;Transwell小室检测迁移能力的改变;流式细胞仪分析细胞周期和凋亡的改变。结果显示,PR在EPCs呈阳性表达;较高浓度的MPA可诱导EPCs凋亡,抑制EPCs的增殖,将细胞周期阻滞在S期,并降低EPCs的迁移能力。高浓度MPA可能通过与EPCs的PR结合,抑制EPCs的生长和迁移,抑制血管生成。

This experiment was aimed to study the effects of different concentrations of medroxyprogesterone acetate（MPA） on proliferation,migration and apoptosis of endothelial progenitor cells（EPCs） in vitro and to provide experimental evidence for the use of MPA as anti-angiogenesis drug.We separated EPCs from bone marrow of a beagle dog and identified the expression of progesterone receptor（PR）in EPCs by immunocytochemistry.Proliferation tests（MTT analysis） were performed with EPCs in response to different concentration of MPA every 24 h for 7 consecutive days,the growth curve of these EPCs was obtained then.The inhibition rates were also obtained from MTT assay performed with EPCs exposed to different concentration of MPA.The migration tests were performed with EPCs in response to different concentrations of MPA.The cell cycle and apoptosis of EPCs exposed to different concentrations of MPA were analyzed by use of flow cytometry.Results： Immunohistochemical staining showed that EPCs were positive to PR.High concentration of MPA had significant inhibition effect on the growth of EPCs.This effect was time-and dose-dependent.But the low concentration of MPA had not have such effect,EPCs exposed to high concentraion of MPA were found arrested in S phase,and the apoptosis rate increased.The migration ability of EPCs exposed to high concentration of MPA was also damaged.Conclusion：High concentration of MPA can induce EPCs＇ apoptosis and inhibit their growth and migration.All these biologicl effects of MPA may be achieved through PR on EPCs.