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目的观察兔颈动脉内支架置入后,血管平滑肌细胞(VSMC)的增殖及c-myc原癌基因的表达。方法将国产铂-铱合金支架置入16只家兔颈动脉,术后7、14、30和90d处死动物,行苏木素伊红(HE)和Masson三色染色、c-myc蛋白免疫组化染色及原位杂交。用透射电镜观察术后14d,VSMC超微结构的变化。结果术后7d,中膜VSMC由收缩型变为合成型,内弹力板消失,偶见炎性细胞浸润,1例血管腔内出现不完全血栓形成。术后14d,新生内膜增生明显,主要由合成型及过渡型VSMC组成。术后30d,新生内膜增生更加明显,主要为收缩型和少量过渡型VSMC及细胞外基质组成。术后90d,内弹力板恢复为弯曲的连续状,其上附着多层内皮细胞,VSMC为收缩型。术后14d透射电镜显示,合成型VSMC呈圆形或椭圆形,粗面内质网及线粒体非常丰富。支架置入后,兔颈动脉新生内膜中c-myc蛋白免疫组化及原位杂交均呈阳性,正常对照血管呈阴性。结论兔颈动脉内置入支架后,可引起VSMC中c-myc基因表达增强,其与VSMC的增殖密切相关,在支架内再狭窄的形成中发挥重要作用。
Objective To observe the proliferation of vascular smooth muscle cells (VSMC) and the expression of c-myc proto-oncogene after rabbit carotid artery stenting. Methods Domestic platinum-iridium stent was placed in the carotid artery of 16 rabbits. Animals were sacrificed at 7, 14, 30 and 90 days after operation. HE and Masson trichrome staining and c-myc protein immunohistochemical staining And in situ hybridization. Transmission electron microscopy was used to observe the ultrastructural changes of VSMC 14 days after operation. Results At 7 days after operation, VSMCs in the media changed from contractile to synthetic, with disappearance of endoluminal plate, inflammatory cell infiltration occasionally, and incomplete thrombosis in 1 vessel. After 14 days, neointimal hyperplasia was obvious, mainly composed of synthetic and transitional VSMC. After 30 days, neointimal hyperplasia was more obvious, mainly shrinkage and a small amount of transitional VSMC and extracellular matrix composition. At 90 days after operation, the internal elastic plate was restored to a curved continuous shape, with multiple layers of endothelial cells attached thereon. VSMCs were contracted. Transmission electron microscopy 14 days after surgery showed that the synthetic VSMC was round or oval, rough endoplasmic reticulum and mitochondria is very rich. After stent implantation, c-myc protein in neointimal hyperplasia of rabbit carotid artery was positive by immunohistochemistry and in situ hybridization. The normal control blood vessels were negative. Conclusion The carotid arteries inserted into scaffolds can induce the expression of c-myc gene in VSMCs, which is closely related to the proliferation of VSMCs and play an important role in the formation of in-stent restenosis.