聚对二氧环己酮血管外支架抑制移植静脉内膜增生的机制

Inhibitory effect of polydioxanone suture external stent on the vein graft neointima thickening and the possible mechanism

目的构建可降解性聚对二氧环己酮（PDS）血管外支架抑制移植静脉内膜增生的动物模型，探讨PDS外支架抑制移植静脉内膜增生的作用及其机制。方法建立兔颈外静脉移植模型，24只新西兰大白兔分为单纯移植组（n=12）和PDS外支架组（n=12）。术后4周及12周取出移植静脉，测量移植静脉内膜、中层面积及厚度，免疫组织化学法和实时荧光定量逆转录-聚合酶链反应（RT-PCR）法检测增殖细胞核抗原（PCNA）、转化生长因子-β1（TGF-β1）和肾素-血管紧张素Ⅱ受体1（AT1R）表达。结果24只兔均存活，移植血管全部通畅。外支架组中膜面积、内膜面积、中膜厚度、内膜厚度各值皆小于单纯移植组，差异有统计学意义（P〈0．05）。免疫组织化学与RT—PCR检测表明血管外支架组TGF-β1在外膜中过度表达，而中膜和内膜表达减少。术后4周，外支架组AT1R表达水平低于对照组，12周时，两组AT1R表达水平都降低，差异无统计学意义（P〉0．05）。结论大孔隙、非限制性PDS血管外支架通过形成新生外膜、调节细胞因子再分布等机制有效地抑制内膜和中膜的增生，其用于抑制移植静脉内膜增生是可行的。

Objective To evaluate the effect of a biodegradable external stent on intimal vein graft thickening in an arteriovenous bypass grafting model, and study its possible mechanism. Methods Twenty-four rabbits underwent carotid interposition bypass via ipsilateral jugular vein. Half received the polydioxanone stent （PDS group） and half a simple vein graft （controls）. Group subsets received external stent removal or sham-control exploration at 4th and 12th week. Each of the specimens was detected for pathological and molecular biological examination. Results At 4th and 12th week the PDS group had significantly less medial and intimal thickening than the control group （ P 〈 0.05 ）, and there were fewer proliferating smooth muscle cells and extra cellular matrix formation than the control group at every interval. The proliferating cell nuclear antigen （PCNA） and angiotensin Ⅱ type 1 receptor （AT1 R） were over-expressed in the tunica media and intima in control group. The transforming growth factor-β1 （TGF-β1） was expressed mostly in adventitia in PDS group. Conclusion An macro-porous nonrestrictive, PDS external stent can ef fectively inhibit the intimal hyperplasia in vein bypass grafts, which might be contributed to the re-distrlbution of TGF-β1 and AT1R.