SDF-1 plays a key role in the repairing and remodeling process on rat allo-orthotopic abdominal aorta grafts

SDF-1 plays a key role in the repairing and remodeling process on rat allo-orthotopic abdominal aorta grafts
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DOI:
10.1016/j.transproceed.2006.10.020
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发表时间:
2007-01-01
影响因子:
0.9
通讯作者:
Li, Y.
Li, Y.
中科院分区:
医学4区
文献类型:
--
作者:
Gao, C.;Li, Y.

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背景我们以前的研究表明,长期冷保存促进大鼠腹主动脉移植物的新生内膜形成和重塑,但延迟随后的动脉硬化。这种现象的机制仍然不清楚。在这项研究中,我们研究了基质细胞衍生因子-1(SDF-1)是否可以在招募干细胞修复和重塑腹主动脉移植物受损内膜中发挥作用。雄性Spague-Dawley大鼠接受来自雄性Wistar大鼠的腹主动脉移植物。进行苏木素和伊红染色,通过测量新生内膜厚度来评估移植主动脉的结构。免疫组织化学染色检测SDF-1的表达。RT-PCR证实了SDF-1在干细胞上表达的唯一天然受体CXCR 4的表达。SDF-1抗体治疗组的新生内膜厚度不明显; SDF-1的表达与移植物的新生内膜厚度之间存在显著相关性。CXCR 4在正常腹主动脉瘤组织中无表达,在移植腹主动脉瘤组织中有表达。长时间的冷缺血可以通过选择性地通过SDF-1将干细胞化学吸引到受损的内膜来延迟移植物的动脉硬化,SDF-1的存在可以预测移植物动脉硬化和随后的慢性移植物功能障碍(CGD)的发展。SDF-1抗体通过阻断这种化学吸引作用减缓了内皮嵌合。在霉酚酸酯和FK 506的基础上,SDF-I抗体可能成为降低CGD发生率的一种新的有效策略。
Background. Our previous study demonstrated that prolonged cold preservation promoted neointima formation and remodeling but delayed the subsequent arteriosclerosis of rat abdominal aorta grafts. The mechanisms of this phenomenon remain obscure. In this study, we investigated whether stromal cell derived factor-1 (SDF-1) could play a role in recruiting stem cells to repair and remodel the damaged intima of abdominal aorta grafts.Methods. Male Spague-Dawley rats received abdominal aorta grafts from male Wistar rats. Hematoxylin and eosin staining was performed to assess the structure of graft aortas by measuring the neointimal thickness. Immunohistochernical staining detected SDF-1 expression. RT-PCR demonstrated the expression of CXCR4, the only known natural receptor of SDF-1 expression on stem cells.Results. The neointimal thickness of the SDF-1 antibody-treated group was inconspicuous; a significant relationship existed between the expression of SDF-1 and the neointimal thickness of the grafts. Furthermore, no CXCR4 was detected in normal abdominal aortas, but it was observed in the grafted abdominal aorta.Conclusion. Prolonged cold ischemia may delay the graft's arteriosclerosis by selectively chemoattracting stem cells to the damaged intima through SDF-1, the presence of which may predict graft arteriosclerosis and the subsequent development of chronic graft dysfunction (CGD). The SDF-1 antibody slowed the endothelial chimerism by blocking this chemoattration. In addition to mycophenolate mofetil and FK 506, SDF-I antibody might be a new potential effective strategy to decrease the frequency of CGD.