基质细胞衍生因子1α介导小鼠内皮祖细胞修复损伤血管内膜
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国家自然科学基金(30470729和30400517)


Involvement of Stromal Cell-Derived Factor-1—CXCR4 Axis in Recruitment of Endothelial Progenitor Cell and Reendotheliazation After Vascular Injury in Mice
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    摘要:

    目的探讨损伤血管局部表达的基质细胞衍生因子1α是否能介导内皮祖细胞参与损伤血管的再内皮化,抑制新生内膜的增生。方法培养、获取小鼠骨髓源性内皮祖细胞,采用改良的Boyden小室测定基质细胞衍生因子1α诱导的内皮祖细胞迁移及AMD3100(CXCR4的拮抗剂)对其的影响。分别将内皮祖细胞培养基、内皮祖细胞及AMD3100孵育过的内皮祖细胞经心脏穿刺注射给颈动脉损伤小鼠,在14天后取损伤血管检测内皮祖细胞募集情况、再内皮化情况及新生内膜增生情况。结果基质细胞衍生因子1α能诱导内皮祖细胞迁移(与对照组比较p<0.01),AMD3100能有效阻断该作用(AMD3100组与对照组比较p>0.05)。较多注射的内皮祖细胞成功归巢到损伤血管处(14.2±3.6个/切片),AMD3100孵育过的内皮祖细胞仅少量可成功归巢(4.0±2.5个/切片);内皮祖细胞注射能加速损伤血管的再内皮化(内皮祖细胞移植组比对照组:83.45%±5.44%比66.46%±6.16%,p<0.01),AMD3100孵育过的内皮祖细胞注射则无效(68.02%±6.68%,与对照组比较p>0.05);内皮祖细胞移植组新生内膜增生厚度(19237±1875μm2)和内膜中膜比值(0.94±0.12)均小于对照组(34676±2412μm2和1.77±0.18)及AMD3100组(32451±2081μm2和1.60±0.17)(p<0.01)。结论基质细胞衍生因子1/CXCR-4在介导移植的内皮祖细胞修复损伤血管内膜中起重要作用。

    Abstract:

    Aim To investigate the involvement of stromal cell-derived factor-1(SDF-1)/CXCR4 Axis in recruitment of endothelial progenitor cell(EPC)and reendotheliazation after vascular injury.Methods EPC migration induced by SDF-1α was determined with modified Boyden chamber assay.Treatment of mice after carotid injury with EPC or EPC coincubated with AMD3100(an antagonist of CXCR4),recruitment of EPC,reendotheliazation and neointimal lesion area were determined 14 d later.Results SDF-1α profoundly enhanced EPC migration(p<0.01),but could not enhance migration of EPC treated with AMD3100(p>0.05).Transfused EPC were strictly restricted to the injury site(14.2±3.6 cell/section),and lectin binding confirmed the endothelial phenotype,but only few EPC coincubated with AMD3100 were recruited to the injury site(4.0±2.5 cells/section).Treatment with EPC caused enhanced reendothelialization(83.45%±5.44%,p<0.01)associated with a reduction of neointima formation(19 237±1 875 μm2,p<0.01)compared with isotype control(66.46%±6.16%,34 676±2 412 μm2);treatment with EPC coincubated with AMD3100 caused no enhanced reendothelialization(68.02%±6.68%,p>0.05)and no reduction of neointima formation(32 451±2 081 μm2,p>0.05)compared with isotype control.Conclusions Stromal cell-derived factor-1/CXCR4 Axis plays an instrumental role in recruitment of EPC and reendotheliazation after vascular injury in mice.

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尹扬光,黄岚,赵晓辉,于世勇,方玉强,赵景红,崔斌.基质细胞衍生因子1α介导小鼠内皮祖细胞修复损伤血管内膜[J].中国动脉硬化杂志,2007,15(1):6~10.

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  • 收稿日期:2006-05-29
  • 最后修改日期:2006-09-18
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