兔自体颈动脉移植于静脉后形态学及分子改变

来源 :中国分子心脏病学杂志 | 被引量 : 0次 | 上传用户:axcom
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目的以往的研究已证实动脉移植到静脉后,即使在高血脂状态下,也不发生粥样硬化,而是发生萎缩样改变,提示了血流动力学特别是切应力在动脉粥样斑块形成和血管重构中的作用。为探讨移植后动脉重构的机理,该文对移植动脉段进行了细胞分子生物学研究。方法建立动脉移植到静脉的新西兰白兔模型,6个时间点后取材,HE染色光镜下观察血管内、中膜厚度与面积;扫描电镜观察内皮变化,透射电镜观察超微结构改变;TUNEL方法观察细胞凋亡状况,RT-PCR检测基因表达水平。结果HE染色发现移植动脉在极低切应力状态下,随时间推移,除管壁发生“类静脉化”的萎缩样改变外,管腔面积先减小后增加;TUNEL结果显示移植动脉发生了细胞凋亡,而且凋亡先发于血管内膜细胞,进而过度到中层,最后累及外膜;通过弹力纤维和胶原纤维双染色证实,弹力纤维在整个过程中并未有显著数量改变,而胶原纤维却发生崩解,最终导致管壁萎缩;术后一周移植动脉的MMP2和MMP9表达明显增高,以后渐下降。结论低切应力作用于血管内膜层细胞致使其凋亡继而由内而外信号转递的过程,这构成了移植动脉发生萎缩样变的基础;胶原纤维的崩解在移植动脉萎缩样变过程中也发挥了重要作用,伴随着MMP表达的上调。 PURPOSE Previous studies have demonstrated that aortic aorta does not undergo atherosclerosis even after hyperplasia, suggesting that hemodynamics, especially shear stress, is associated with atherosclerotic plaque formation And the role of vascular remodeling. In order to explore the mechanism of arterial remodeling after transplantation, the molecular biology of the transplanted artery was studied in this paper. Methods The New Zealand white rabbits were transplanted into arteries and veins. Six time points were taken. The thickness and area of ​​vascular intima and media were observed under light microscope. The changes of endothelial cells were observed by scanning electron microscope. The ultrastructural changes were observed by transmission electron microscopy. The apoptosis status was observed, and the gene expression level was detected by RT-PCR. RESULTS: Under the condition of very low shear stress, the lumen area decreased firstly and then increased with the exception of the atrophy of the “vein-like” vessel wall under the condition of very low shear stress. HE staining showed that the graft artery occurred Apoptosis and apoptosis in the endometrial cells, and then excessive to the middle, and finally involving the outer membrane; elastic fibers and collagen fibers by double staining confirmed that the elastic fibers in the entire process did not change in significant quantities, and Collagenous fibers collapsed, eventually leading to atrophy of the tube wall. The expression of MMP2 and MMP9 was significantly increased in the arteries after transplantation one week after operation, and then gradually decreased. CONCLUSION: The low shear stress acts on the vascular endothelium cells to induce apoptosis and then transmit the signal from the inside to the outside, which forms the basis of the atrophy of the graft artery. The disintegration of the collagen fibers in the process of graft atrophy Also play an important role, accompanied by an increase in MMP expression.
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