基质细胞衍生因子1α参与血管损伤后内皮祖细胞动员及再内皮化

Stromal Cell-Derived factor-1 α Involves in Mobilization of Endothelial Progenitor Cells and Reendothelialization After Artery Injury

  • 摘要: 背景基质细胞衍生因子1(SDF-1)在干/祖细胞动员和归巢过程中起关键作用,最近的研究显示SDF-1在损伤动脉局部强表达,且在稳定性冠心病中其血浆浓度明显高于不稳定性患者。目的探讨 SDF-1是否参与血管损伤后的内皮祖细胞(EPC)动员。方法采用0.35 mm 直径的弹性导丝损伤小鼠左颈总动脉,逆转录—聚合酶链反应(RT-PCR)和 Western blot 检测术后各时间点损伤动脉 SDF-1α的表达变化;采用 SDF-1α酶联免疫吸附测定试剂盒测定术后各时间点外周血及骨髓 SDF-1α浓度的变化;流式细胞仪检测术后各时间点外周血 EPC(Sca-1+VEGFR2+细胞)数量。给颈动脉损伤小鼠注射 SDF-1α单克隆抗体,检测术后各时间点外周血 EPC 数量,及采用 Evans blue 染色和病理形态学分析检测14d 后损伤动脉的再内皮化面积和新生内膜增生情况。结果动脉损伤后1 d 即可见损伤血管局部 SDF-1α表达明显上调,3 d 时达到高峰。外周血 SDF-1α浓度在术后1 d 明显升高,3 d 时达到顶峰,而骨髓 SDF-1α浓度在动脉损伤后明显下降,同时外周血 EPC 数量明显升高(与假手术组比较,P<0.01)。在 SDF-1α单克隆抗体注射组,仅术后1 d 时外周血 EPC 数量轻度升高,高于假手术组(P<0.05),但明显低于 IgG1同型对照组(P<0.05),其余各时间点未检测到外周血 EPC 数量明显变化(与假手术组比较,P>0.05)。术后14 d SDF-1α单克隆抗体注射组损伤动脉再内皮化面积明显明显低于 IgG1同型对照组(P<0.01),而新生内膜面积两组间无明显差异(P>0.05)。结论 SDF-1参与介导血管损伤后的 EPC 动员,其介导动员的 EPC参与调节动脉内膜损伤后的再内皮化过程。

     

    Abstract: Background Stromal cell-derived factor-1α(SDF-1α)has been demonstrated to be essential for stern cell mobilization/homing.Recent evidence indicates that SDF-1α has been expressed in injured carotid arter- ies.Besides,high SDF-1α plasma levels are clinically associated with stable coronary artery disease.Objective To investigate whether SDF 1 involves in mobilization of endothelial progenitor cells(EPC)and reendothelialization after vascular injury.Methods SDF-1α was detected by RT-PCR and Western blot in carotid arteries of mice at different time points after wire-induced injury.SDF-1α determination in peripheral blood samples and BM was per- formed by SDF-1α enzyme-linked immunosorbent assay(ELISA)kit.EPC in peripheral blood collected at different time points after vascular injury were quantified by flow cytornetry.In subgroup,blocking SDF-1 rnonoclonal anti- body was injected,peripheral blood EPC were quantified after vascular injury and reendothelialization of injured ar- teries was determined 14 days later.Results Expression of SDF-1α was evident at day 1,and peaked at day 3 after arterial injury.A rise in plasmatic concentration of SDF-1α and a significant reduction of SDF-1α in bone marrow concentration was noticed at all time points following injury.The amount of circulating EPC was increased shortly after induction of vascular injury and persisted up to 7 days(P<0.01).In SDF-1α antibody-treated mice,only a little rise in the amount of circulating EPC was noted at day 1 after vascular injury and reduced reendothelialization area was observed 14 days later(P<0.01).Conclusion SDF-1α plays an instrumental role in EPC mobilization and reendothelialization after vascular injury in mice.

     

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